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1.
Int. j. morphol ; 41(6): 1887-1896, dic. 2023. ilus, graf
Article in English | LILACS | ID: biblio-1528807

ABSTRACT

SUMMARY: The therapeutic effect of a granulocyte-colony stimulating factor (G-CSF) biosimilar drug, zarzio, on non-alcoholic fatty liver disease (NAFLD) in a rat model was investigated in this study. Thirty-two rats were randomly divided into four groups. Groups I and II were fed a standard laboratory diet, whereas groups III and IV were fed a high fat diet (HFD) for 14 weeks. After 12 weeks of feeding, groups I and III were administered normal saline, and groups II and IV were intraperitoneally administered zarzio (200 mg/kg/day) for two consecutive weeks. Hematoxylin-eosin (H&E) staining was used to assess hepatic and pancreatic morphology in all groups, oil red O (ORO) staining for lipid accumulation, Masson's staining for fibrosis, and immunohistochemistry assay for hepatic protein expression of insulin receptor substrate 1 (IRS1), nuclear factor erythroid 2-related factor 2 (Nrf2), tumour necrosis factor alpha (TNF-α) and pancreatic caspase-3. The NAFLD rats (group III) developed hepatic steatosis with increased lipid accumulation, perisinusoidal fibrosis, upregulated IRS1, TNF-α (all P<0.05) without a significant increase in Nrf2 protein expression compared with normal control. In comparison, model rats treated with zarzio (group IV) showed significant rejuvenation of the hepatic architecture, reduction of fat accumulation, and fibrosis. This was accompanied by the upregulation of Nrf2, downregulation of IRS1 and TNF-α protein expression (all P<0.05). No correlation was detected between NAFLD and non-alcoholic fatty pancreas disease (NAFPD). However, the pancreatic β-cells in group III showed increased caspase-3 expression, which was decreased (P<0.05) in group IV. In conclusion, zarzio ameliorates NAFLD by improving the antioxidant capacity of liver cells, reducing hepatic IRS1, TNF-α protein expression and pancreatic β-cells apoptosis, suggesting that zarzio could be used as a potential therapy for NAFLD.


En este estudio se investigó el efecto terapéutico de un fármaco biosimilar del factor estimulante de colonias de granulocitos (G-CSF), zarzio, sobre la enfermedaddel hígado graso no alcohólico (NAFLD) en un modelo de rata. Treinta y dos ratas se dividieron aleatoriamente en cuatro grupos. Los grupos I y II fueron alimentados con una dieta estándar de laboratorio, mientras que los grupos III y IV fueron alimentados con una dieta alta en grasas (HFD) durante 14 semanas. Después de 12 semanas de alimentación, a los grupos I y III se les administró solución salina normal, y a los grupos II y IV se les administró zarzio por vía intraperitoneal (200 mg/kg/ día) durante dos semanas consecutivas. Se utilizó tinción de hematoxilina-eosina (H&E) para evaluar la morfología hepática y pancreática en todos los grupos, tinción con rojo aceite O (ORO) para la acumulación de lípidos, tinción de Masson para la fibrosis y ensayo de inmunohistoquímica para la expresión de la proteína hepática del sustrato 1 del receptor de insulina (IRS1), factor nuclear eritroide 2 relacionado con el factor 2 (Nrf2), factor de necrosis tumoral alfa (TNF-α) y caspasa-3 pancreática. Las ratas NAFLD (grupo III) desarrollaron esteatosis hepática con aumento de la acumulación de lípidos, fibrosis perisinusoidal, IRS1 y TNF-α regulados positivamente (todos P <0,05) sin un aumento significativo en la expresión de la proteína Nrf2 en comparación con el control normal. En comparación, las ratas modelo tratadas con zarzio (grupo IV) mostraron un rejuvenecimiento significativo de la arquitectura hepática, una reducción de la acumulación de grasa y fibrosis. Esto estuvo acompañado por la regulación positiva de Nrf2, la regulación negativa de la expresión de la proteína IRS1 y TNF-α (todas P <0,05). No se detectó correlación entre NAFLD y la enfermedad del páncreas graso no alcohólico (NAFPD). Sin embargo, las células β pancreáticas en el grupo III mostraron una mayor expresión de caspasa-3, que disminuyó (P <0,05) en el grupo IV. En conclusión, zarzio mejora la NAFLD al mejorar la capacidad antioxidante de las células hepáticas, reduciendo el IRS1 hepático, la expresión de la proteína TNF-α y la apoptosis de las células β pancreáticas, lo que sugiere que zarzio podría usarse como una terapia potencial para la NAFLD.


Subject(s)
Animals , Male , Rats , Granulocyte Colony-Stimulating Factor/administration & dosage , Biosimilar Pharmaceuticals/administration & dosage , Non-alcoholic Fatty Liver Disease/drug therapy , Immunohistochemistry , Tumor Necrosis Factor-alpha/drug effects , Disease Models, Animal , Insulin-Secreting Cells/drug effects , NF-E2-Related Factor 2 , Caspase 3 , Diet, High-Fat/adverse effects
2.
Chinese Journal of Natural Medicines (English Ed.) ; (6): 830-841, 2023.
Article in English | WPRIM | ID: wpr-1010994

ABSTRACT

In the context of non-alcoholic fatty liver disease (NAFLD), characterized by dysregulated lipid metabolism in hepatocytes, the quest for safe and effective therapeutics targeting lipid metabolism has gained paramount importance. Sanhuang Xiexin Tang (SXT) and Baihu Tang (BHT) have emerged as prominent candidates for treating metabolic disorders. SXT combined with BHT plus Cangzhu (SBC) has been used clinically for Weihuochisheng obese patients. This retrospective analysis focused on assessing the anti-obesity effects of SBC in Weihuochisheng obese patients. We observed significant reductions in body weight and hepatic lipid content among obese patients following SBC treatment. To gain further insights, we investigated the effects and underlying mechanisms of SBC in HFD-fed mice. The results demonstrated that SBC treatment mitigated body weight gain and hepatic lipid accumulation in HFD-fed mice. Pharmacological network analysis suggested that SBC may affect lipid metabolism, mitochondria, inflammation, and apoptosis-a hypothesis supported by the hepatic transcriptomic analysis in HFD-fed mice treated with SBC. Notably, SBC treatment was associated with enhanced hepatic mitochondrial biogenesis and the inhibition of the c-Jun N-terminal kinase (JNK)/nuclear factor-kappa B (NF-κB) and extracellular signal-regulated kinase (ERK)/NF-κB pathways. In conclusion, SBC treatment alleviates NAFLD in both obese patients and mouse models by improving lipid metabolism, potentially through enhancing mitochondrial biogenesis. These effects, in turn, ameliorate inflammation in hepatocytes.


Subject(s)
Humans , Mice , Animals , Non-alcoholic Fatty Liver Disease/metabolism , NF-kappa B/metabolism , Organelle Biogenesis , Retrospective Studies , Mice, Inbred C57BL , Obesity/metabolism , Liver , Inflammation/metabolism , Body Weight , Lipid Metabolism , Lipids , Diet, High-Fat/adverse effects
3.
China Journal of Chinese Materia Medica ; (24): 1760-1769, 2023.
Article in Chinese | WPRIM | ID: wpr-981393

ABSTRACT

The present study aimed to investigate the effect of diosgenin on mammalian target of rapamycin(mTOR), fatty acid synthase(FASN), hypoxia inducible factor-1α(HIF-1α), and vascular endothelial growth factor A(VEGFA) expression in liver tissues of rats with non-alcoholic fatty liver disease(NAFLD) and explore the mechanism of diosgenin on lipogenesis and inflammation in NAFLD. Forty male SD rats were divided into a normal group(n=8) fed on the normal diet and an experimental group(n=32) fed on the high-fat diet(HFD) for the induction of the NAFLD model. After modeling, the rats in the experimental group were randomly divided into an HFD group, a low-dose diosgenin group(150 mg·kg~(-1)·d~(-1)), a high-dose diosgenin group(300 mg·kg~(-1)·d~(-1)), and a simvastatin group(4 mg·kg~(-1)·d~(-1)), with eight rats in each group. The drugs were continuously given by gavage for eight weeks. The levels of triglyceride(TG), total cholesterol(TC), low-density lipoprotein cholesterol(LDL-C), alanine transaminase(ALT), and aspartate transaminase(AST) in the serum were detected by the biochemical method. The content of TG and TC in the liver was detected by the enzyme method. Enzyme-linked immunosorbent assay(ELISA) was used to measure interleukin 1β(IL-1β) and tumor necrosis factor α(TNF-α) in the serum. Lipid accumulation in the liver was detected by oil red O staining. Pathological changes of liver tissues were detected by hematoxylin-eosin(HE) staining. The mRNA and protein expression levels of mTOR, FASN, HIF-1α, and VEGFA in the liver of rats were detected by real-time fluorescence-based quantitative polymerase chain reaction(PCR) and Western blot, respectively. Compared with the normal group, the HFD group showed elevated body weight and levels of TG, TC, LDL-C, ALT, AST, IL-1β, and TNF-α(P<0.01), increased lipid accumulation in the liver(P<0.01), obvious liver steatosis, up-regulated mRNA expression levels of mTOR, FASN, HIF-1α, and VEGFA(P<0.01), and increased protein expression levels of p-mTOR, FASN, HIF-1α, and VEGFA(P<0.01). Compared with the HFD group, the groups with drug treatment showed lowered body weight and levels of TG, TC, LDL-C, ALT, AST, IL-1β, and TNF-α(P<0.05, P<0.01), reduced lipid accumulation in the liver(P<0.01), improved liver steatosis, decreased mRNA expression levels of mTOR, FASN, HIF-1α, and VEGFA(P<0.05, P<0.01), and declining protein expression levels of p-mTOR, FASN, HIF-1α, and VEGFA(P<0.01). The therapeutic effect of the high-dose diosgenin group was superior to that of the low-dose diosgenin group and the simvastatin group. Diosgenin may reduce liver lipid synthesis and inflammation and potentiate by down-regulating the mTOR, FASN, HIF-1α, and VEGFA expression, playing an active role in preventing and treating NAFLD.


Subject(s)
Rats , Male , Animals , Non-alcoholic Fatty Liver Disease/metabolism , Vascular Endothelial Growth Factor A/metabolism , Tumor Necrosis Factor-alpha/metabolism , Cholesterol, LDL , Rats, Sprague-Dawley , Liver , Inflammation/metabolism , Diet, High-Fat/adverse effects , TOR Serine-Threonine Kinases/metabolism , RNA, Messenger/metabolism , Body Weight , Mammals
4.
China Journal of Chinese Materia Medica ; (24): 1751-1759, 2023.
Article in Chinese | WPRIM | ID: wpr-981392

ABSTRACT

Hepatic lipid deposition is one of the basic manifestations of obesity, and nowadays pharmacological treatment is the most important tool. Punicalagin(PU), a polyphenol derived from pomegranate peel, is a potential anti-obesity substance. In this study, 60 C57BL/6J mice were randomly divided into a normal group and a model group. After establishing a model of simple obesity with a high-fat diet for 12 weeks, the successfully established rat models of obesity were then regrouped into a model group, an orlistat group, a PU low-dose group, a PU medium-dose group, and a PU high-dose group. The normal group was kept on routine diet and other groups continued to feed the high-fat diet. The body weight and food intake were measured and recorded weekly. After 8 weeks, the levels of the four lipids in the serum of each group of mice were determined by an automatic biochemical instrument. Oral glucose tole-rance and intraperitoneal insulin sensitivity were tested. Hemoxylin-eosin(HE) staining was applied to observe the hepatic and adipose tissues. The mRNA expression levels of peroxisome proliferators-activated receptor γ(PPARγ) and C/EBPα were determined by real-time quantitative polymerase chain reaction(Q-PCR), and the mRNA and protein expression levels of adenosine 5'-monophosphate-activated protein kinase(AMPK), anterior cingulate cortex(ACC), and carnitine palmitoyltransferase 1A(CPT1A) were determined by Western blot. Finally, the body mass, Lee's index, serum total glyceride(TG), serum total cholesterol(TC), and low-density lipoprotein cholesterol(LDL-C) levels were significantly higher and high-density lipoprotein cholesterol(HDL-C) levels were significantly lower in the model group as compared with the normal group. The fat deposition in the liver was significantly increased. The mRNA expression levels of hepatic PPARγ and C/EBPα and the protein expression level of ACC were increased, while the mRNA and protein expression levels of CPT-1α(CPT1A) and AMPK were decreased. After PU treatment, the above indexes of obese mice were reversed. In conclusion, PU can decrease the body weight of obese mice and control their food intake. It also plays a role in the regulation of lipid metabolism and glycometabolism metabolism, which can significantly improve hepatic fat deposition. Mechanistically, PU may regulate liver lipid deposition in obese mice by down-regulating lipid synthesis and up-regulating lipolysis through activation of the AMPK/ACC pathway.


Subject(s)
Rats , Mice , Animals , Mice, Obese , AMP-Activated Protein Kinases/metabolism , PPAR gamma/metabolism , Mice, Inbred C57BL , Liver/metabolism , Obesity/genetics , Body Weight , Lipid Metabolism , Diet, High-Fat/adverse effects , Lipids , Cholesterol
5.
China Journal of Chinese Materia Medica ; (24): 2146-2159, 2023.
Article in Chinese | WPRIM | ID: wpr-981346

ABSTRACT

On the basis of establishing the prescription of Xinjianqu and clarifying the increase of the lipid-lowering active ingredients of Xinjianqu by fermentation, this paper further compared the differences in the lipid-lowering effects of Xinjianqu before and after fermentation, and studied the mechanism of Xinjianqu in the treatment of hyperlipidemia. Seventy SD rats were randomly divided into seven groups, including normal group, model group, positive drug simvastatin group(0.02 g·kg~(-1)), and low-dose and high-dose Xinjianqu groups before and after fermentation(1.6 g·kg~(-1) and 8 g·kg~(-1)), with ten rats in each group. Rats in each group were given high-fat diet continuously for six weeks to establish the model of hyperlipidemia(HLP). After successful modeling, the rats were given high-fat diet and gavaged by the corresponding drugs for six weeks, once a day, to compare the effects of Xinjianqu on the body mass, liver coefficient, and small intestine propulsion rate of rats with HLP before and after fermentation. The effects of Xinjianqu before and after fermentation on total cholesterol(TC), triacylglyceride(TG), high-density lipoprotein cholesterol(HDL-C), low-density lipoprotein cholesterol(LDL-C), alanine aminotransferase(ALT), aspartate aminotransferase(AST), blood urea nitrogen(BUN), creatinine(Cr), motilin(MTL), gastrin(GAS), and the Na~+-K~+-ATPase levels were determined by enzyme-linked immunosorbent assay(ELISA). The effects of Xinjianqu on liver morphology of rats with HLP were investigated by hematoxylin-eosin(HE) staining and oil red O fat staining. The effects of Xinjianqu on the protein expression of adenosine 5'-monophosphate(AMP)-activated protein kinase(AMPK), phosphorylated AMPK(p-AMPK), liver kinase B1(LKB1), and 3-hydroxy-3-methylglutarate monoacyl coenzyme A reductase(HMGCR) in liver tissues were investigated by immunohistochemistry. The effects of Xinjianqu on the regulation of intestinal flora structure of rats with HLP were studied based on 16S rDNA high-throughput sequencing technology. The results showed that compared with those in the normal group, rats in the model group had significantly higher body mass and liver coefficient(P<0.01), significantly lower small intestine propulsion rate(P<0.01), significantly higher serum levels of TC, TG, LDL-C, ALT, AST, BUN, Cr, and AQP2(P<0.01), and significantly lower serum levels of HDL-C, MTL, GAS, Na~+-K~+-ATP levels(P<0.01). The protein expression of AMPK, p-AMPK, and LKB1 in the livers of rats in the model group was significantly decreased(P<0.01), and that of HMGCR was significantly increased(P<0.01). In addition, the observed_otus, Shannon, and Chao1 indices were significantly decreased(P<0.05 or P<0.01) in rat fecal flora in the model group. Besides, in the model group, the relative abundance of Firmicutes was reduced, while that of Verrucomicrobia and Proteobacteria was increased, and the relative abundance of beneficial genera such as Ligilactobacillus and Lachnospiraceae_NK4A136_group was reduced. Compared with the model group, all Xinjianqu groups regulated the body mass, liver coefficient, and small intestine index of rats with HLP(P<0.05 or P<0.01), reduced the serum levels of TC, TG, LDL-C, ALT, AST, BUN, Cr, and AQP2, increased the serum levels of HDL-C, MTL, GAS, and Na~+-K~+-ATP, improved the liver morphology, and increased the protein expression gray value of AMPK, p-AMPK, and LKB1 in the liver of rats with HLP and decreased that of LKB1. Xinjianqu groups could regulate the intestinal flora structure of rats with HLP, increased observed_otus, Shannon, Chao1 indices, and increased the relative abundance of Firmicutes, Ligilactobacillus(genus), Lachnospiraceae_NK4A136_group(genus). Besides, the high-dose Xinjianqu-fermented group had significant effects on body mass, liver coefficient, small intestine propulsion rate, and serum index levels of rats with HLP(P<0.01), and the effects were better than those of Xinjianqu groups before fermentation. The above results show that Xinjianqu can improve the blood lipid level, liver and kidney function, and gastrointestinal motility of rats with HLP, and the improvement effect of Xinjianqu on hyperlipidemia is significantly enhanced by fermentation. The mechanism may be related to AMPK, p-AMPK, LKB1, and HMGCR protein in the LKB1-AMPK pathway and the regulation of intestinal flora structure.


Subject(s)
Rats , Animals , AMP-Activated Protein Kinases/metabolism , Rats, Sprague-Dawley , Cholesterol, LDL , Fermentation , Aquaporin 2/metabolism , Lipid Metabolism , Liver , Lipids , Hyperlipidemias/genetics , Adenosine Triphosphate/pharmacology , Diet, High-Fat/adverse effects
6.
China Journal of Chinese Materia Medica ; (24): 1535-1545, 2023.
Article in Chinese | WPRIM | ID: wpr-970625

ABSTRACT

To compare the pancreatic proteomics and autophagy between Rehmanniae Radix-and Rehmanniae Radix Praeparata-treated mice with type 2 diabetes mellitus(T2DM). The T2DM mouse model was established by high-fat diet coupled with streptozotocin(STZ, intraperitoneal injection, 100 mg·kg~(-1), once a day for three consecutive days). The mice were then randomly assigned into a control group, low-(5 g·kg~(-1)) and high-dose(15 g·kg~(-1)) Rehmanniae Radix groups, low-(150 mg·kg~(-1)) and high-dose(300 mg·kg~(-1)) catalpol groups, low-(5 g·kg~(-1)) and high-dose(15 g·kg~(-1)) Rehmanniae Radix Praeparata groups, low-(150 mg·kg~(-1)) and high-dose(300 mg·kg~(-1)) 5-hydroxymethyl furfuraldehyde(5-HMF) groups, and a metformin(250 mg·kg~(-1)) group. In addition, a normal group was also set and each group included 8 mice. The pancreas was collected after four weeks of administration and proteomics tools were employed to study the effects of Rehmanniae Radix and Rehmanniae Radix Praeparata on protein expression in the pancreas of T2DM mice. The expression levels of proteins involved in autophagy, inflammation, and oxidative stress response in the pancreatic tissues of T2DM mice were determined by western blotting, immunohistochemical assay, and transmission electron microscopy. The results showed that the differential proteins between the model group and Rehmanniae Radix/Rehmanniae Radix Prae-parata group were enriched in 7 KEGG pathways, such as autophagy-animal, which indicated that the 7 pathways may be associated with T2DM. Compared with the control group, drug administration significantly up-regulated the expression levels of beclin1 and phosphorylated mammalian target of rapamycin(p-mTOR)/mTOR and down-regulated those of the inflammation indicators, Toll-like receptor-4(TLR4) and Nod-like receptor protein 3(NLRP3), in the pancreas of T2DM mice, and Rehmanniae Radix showed better performance. In addition, the expression levels of inducible nitric oxide synthase(iNOS), nuclear factor erythroid 2-related factor 2(Nrf2), and heine oxygenase-1(HO-1) in the pancreas of T2DM mice were down-regulated after drug administration, and Rehmanniae Radix Praeparata demonstrated better performance. The results indicate that both Rehmanniae Radix and Rehmanniae Radix Praeparata can alleviate the inflammatory symptoms, reduce oxidative stress response, and increase the autophagy level in the pancreas of T2DM mice, while they exert the effect on different autophagy pathways.


Subject(s)
Mice , Animals , Diabetes Mellitus, Type 2/genetics , Streptozocin/pharmacology , Diet, High-Fat/adverse effects , Proteomics , Inflammation , TOR Serine-Threonine Kinases , Autophagy , Mammals
7.
Braz. j. biol ; 83: e248755, 2023. tab, graf
Article in English | LILACS, VETINDEX | ID: biblio-1350303

ABSTRACT

Abstract Consuming a high-fat diet causes a harmful accumulation of fat in the liver, which may not reverse even after switching to a healthier diet. Different reports dealt with the role of purslane as an extract against high-fat diet; meanwhile, it was necessary to study the potential role of fresh purslane as a hypolipidemic agent. This study is supposed to investigate further the potential mechanism in the hypolipidemic effect of fresh purslane, by measuring cholesterol 7a-hydroxylase (CYP7A1) and low-density lipoprotein receptor (Ldlr). Rats were divided into two main groups: the first one is the normal control group (n=7 rats) and the second group (n=28 rats) received a high fat diet for 28 weeks to induce obesity. Then the high fat diet group was divided into equal four subgroups. As, the positive control group still fed on a high fat diet only. Meanwhile, the other three groups were received high-fat diet supplemented with a different percent of fresh purslane (25, 50 and 75%) respectively. At the end of the experiment, rats were sacrificed and samples were collected for molecular, biochemical, and histological studies. Current study reported that, supplementation of fresh purslane especially at a concentration of 75% play an important role against harmful effects of high-fat diet at both cellular and organ level, by increasing CYP7A1 as well as Ldlr mRNA expression. Also, there were an improvement on the tested liver functions, thyroid hormones, and lipid profile. Fresh purslane plays the potential role as a hypolipidemic agent via modulation of both Ldlr and Cyp7A, which will point to use fresh purslane against harmful effects of obesity.


Resumo O consumo de uma dieta rica em gordura causa um acúmulo prejudicial de gordura no fígado, que pode não reverter mesmo após a mudança para uma dieta mais saudável. Diferentes relatórios trataram do papel da beldroega como um extrato contra uma dieta rica em gordura; entretanto, foi necessário estudar o papel potencial da beldroega fresca como agente hipolipemiante. Este estudo pretende investigar mais profundamente o mecanismo potencial no efeito hipolipidêmico da beldroega fresca, medindo o colesterol 7a-hidroxilase (CYP7A1) e o receptor de lipoproteína de baixa densidade (Ldlr). Os ratos foram divididos em dois grupos principais: o primeiro é o grupo controle normal (n = 7 ratos) e o segundo grupo (n = 28 ratos) recebeu dieta rica em gorduras por 28 semanas para induzir a obesidade. Em seguida, o grupo de dieta rica em gordura foi dividido em quatro subgrupos iguais. Como, o grupo de controle positivo ainda se alimentava apenas com dieta rica em gordura. Enquanto isso, os outros três grupos receberam dieta rica em gordura suplementada com diferentes porcentagens de beldroegas frescas (25%, 50% e 75%), respectivamente. Ao final do experimento, os ratos foram sacrificados e amostras coletadas para estudos moleculares, bioquímica e histológicos. O estudo atual relatou que a suplementação de beldroegas frescas, especialmente a uma concentração de 75%, desempenha papel importante contra os efeitos prejudiciais da dieta rica em gordura em nível celular e orgânico, aumentando a expressão de CYP7A1 e Ldlr mRNA. Além disso, houve melhora nas funções hepáticas testadas, nos hormônios tireoidianos e no perfil lipídico. Beldroegas frescas desempenham papel potencial como agente hipolipemiante por meio da modulação de Ldlr e Cyp7A, o que apontará para o uso de beldroegas frescas contra os efeitos nocivos da obesidade.


Subject(s)
Animals , Rats , Portulaca , Diet, High-Fat/adverse effects , Hypolipidemic Agents , Cholesterol 7-alpha-Hydroxylase , Rats, Sprague-Dawley , Liver
8.
China Journal of Chinese Materia Medica ; (24): 6442-6456, 2023.
Article in Chinese | WPRIM | ID: wpr-1008844

ABSTRACT

The present study aimed to investigate the effect of Xianglian Pills(XLP) on lipid metabolism in obese mice and explore the underlying mechanism based on network pharmacology and intestinal flora. Firstly, network pharmacology was used to predict the possible effect of XLP on obesity. Secondly, an obese mouse model induced by a high-fat diet was established to observe changes in mouse body weight, adiposity index, liver and adipose tissue pathology. Lipid profiles, liver and kidney function markers, insulin content, and the expression of recombinant uncoupling protein 1(UCP-1) and PR structural domain protein 16(PRDM16) were measured. The 16S rRNA gene sequencing technology was used to analyze the changes in the intestinal flora. Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis showed that XLP mainly played a role in improving obesity by regulating lipolysis, type 2 diabetes mellitus, and insulin resistance. The results of animal experiments showed that XLP significantly reduced body weight, adiposity, blood lipid levels, and serum insulin levels in obese mice, while enhancing the expression of UCP-1 and PRDM16 in adipose tissue without causing damage to the liver or kidneys. The 16S rRNA gene sequencing results showed that XLP decreased the Firmicutes/Bacteroidetes(F/B) ratio at the phylum level, increased the relative abundance of Akkermansia and Bacteroides at the family and genus levels, and reduced the abundance of Allobaculum. Therefore, XLP can effectively improve lipid metabolism disorders in high-fat diet-induced obese mice, and the mechanism is related to the improvement of brown adipose function, the browning of white fat, the accelerated lipid metabolism, and the improvement of intestinal flora. However, its effect on promoting the conversion of white adipose to brown adipose still needs to be further studied.


Subject(s)
Mice , Animals , Mice, Obese , Diet, High-Fat/adverse effects , Gastrointestinal Microbiome , Network Pharmacology , RNA, Ribosomal, 16S , Diabetes Mellitus, Type 2/complications , Obesity/genetics , Body Weight , Lipids , Insulin , Transcription Factors , Dyslipidemias/genetics , Mice, Inbred C57BL , Drugs, Chinese Herbal
9.
China Journal of Chinese Materia Medica ; (24): 5304-5314, 2023.
Article in Chinese | WPRIM | ID: wpr-1008728

ABSTRACT

This study aims to observe the effects of diosgenin on the expression of mammalian target of rapamycin(mTOR), sterol regulatory element-binding protein-1c(SREBP-1c), heat shock protein 60(HSP60), medium-chain acyl-CoA dehydrogenase(MCAD), and short-chain acyl-CoA dehydrogenase(SCAD) in the liver tissue of the rat model of non-alcoholic fatty liver disease(NAFLD) and explore the mechanism of diosgenin in alleviating NAFLD. Forty male SD rats were randomized into five groups: a control group, a model group, low-(150 mg·kg~(-1)·d~(-1)) and high-dose(300 mg·kg~(-1)·d~(-1)) diosgenin groups, and a simvastatin(4 mg·kg~(-1)·d~(-1)) group. The rats in the control group were fed with a normal diet, while those in the other four groups were fed with a high-fat diet. After feeding for 8 weeks, the body weight of rats in the high-fat diet groups increased significantly. After that, the rats were administrated with the corresponding dose of diosgenin or simvastatin by gavage every day for 8 weeks. The levels of triglyceride(TG), total cholesterol(TC), alanine transaminase(ALT), and aspartate transaminase(AST) in the serum were determined by the biochemical method. The levels of TG and TC in the liver were measured by the enzyme method. Oil-red O staining was employed to detect the lipid accumulation, and hematoxylin-eosin(HE) staining to detect the pathological changes in the liver tissue. The mRNA and protein levels of mTOR, SREBP-1c, HSP60, MCAD, and SCAD in the liver tissue of rats were determined by real-time fluorescence quantitative polymerase chain reaction(RT-qPCR) and Western blot, respectively. Compared with the control group, the model group showed increased body weight, food uptake, liver index, TG, TC, ALT, and AST levels in the serum, TG and TC levels in the liver, lipid deposition in the liver, obvious hepatic steatosis, up-regulated mRNA and protein expression levels of mTOR and SREBP-1c, and down-regulated mRNA and protein expression levels of HSP60, MCAD, and SCAD. Compared with the model group, the rats in each treatment group showed obviously decreased body weight, food uptake, liver index, TG, TC, ALT, and AST levels in the serum, TG and TC levels in the liver, lessened lipid deposition in the liver, ameliorated hepatic steatosis, down-regulated mRNA and protein le-vels of mTOR and SREBP-1c, and up-regulated mRNA and protein levels of HSP60, MCAD, and SCAD. The high-dose diosgenin outperformed the low-dose diosgenin and simvastatin. Diosgenin may prevent and treat NAFLD by inhibiting the expression of mTOR and SREBP-1c and promoting the expression of HSP60, MCAD, and SCAD to reduce lipid synthesis, improving mitochondrial function, and promoting fatty acid β oxidation in the liver.


Subject(s)
Rats , Male , Animals , Non-alcoholic Fatty Liver Disease/genetics , Sterol Regulatory Element Binding Protein 1/metabolism , Diet, High-Fat/adverse effects , Diosgenin/metabolism , Chaperonin 60/therapeutic use , Rats, Sprague-Dawley , Liver , Signal Transduction , TOR Serine-Threonine Kinases/metabolism , Triglycerides , RNA, Messenger/metabolism , Simvastatin/therapeutic use , Body Weight , Lipid Metabolism , Mammals/metabolism
10.
China Journal of Chinese Materia Medica ; (24): 4438-4445, 2023.
Article in Chinese | WPRIM | ID: wpr-1008698

ABSTRACT

This study aimed to investigate the effect and mechanism of Zuogui Jiangtang Qinggan Formula(ZGJTQG) on the glucolipid metabolism of type 2 diabetes mellitus(T2DM) complicated with non-alcoholic fatty liver disease(NAFLD). NAFLD was induced by a high-fat diet(HFD) in MKR mice(T2DM mice), and a model of T2DM combined with NAFLD was established. Forty mice were randomly divided into a model group, a metformin group(0.067 g·kg~(-1)), and high-and low-dose ZGJTQG groups(29.64 and 14.82 g·kg~(-1)), with 10 mice in each group. Ten FVB mice of the same age were assigned to the normal group. Serum and liver tissue specimens were collected from mice except for those in the normal and model groups after four weeks of drug administration by gavage, and fasting blood glucose(FBG) and fasting insulin(FINS) levels were measured. The levels of total cholesterol(TC), triglyceride(TG), and low-density lipoprotein(LDL) were detected by the single reagent GPO-PAP method. Very low-density lipoprotein(VLDL) was detected by enzyme-linked immunosorbent assay(ELISA). Alanine aminotransferase(ALT) and aspartate ami-notransferase(AST) were determined by the Reitman-Frankel assay. The pathological changes in the liver were observed by hematoxylin-eosin(HE) staining and oil red O staining. Real-time fluorescence-based quantitative polymerase chain reaction(real-time PCR) and Western blot were adopted to detect the mRNA and protein expression of forkhead transcription factor O1(FoxO1), microsomal triglyceride transfer protein(MTP), and apolipoprotein B(APOB) in the liver. The results showed that high-dose ZGJTQG could signi-ficantly reduce the FBG and FINS levels(P<0.05, P<0.01), improve glucose tolerance and insulin resistance(P<0.05, P<0.01), alleviate the liver damage caused by HFD which was reflected in improving liver steatosis, and reduce the serum levels of TC, TG, LDL, VLDL, ALT, and AST(P<0.05, P<0.01) in T2DM mice combined with NAFLD. The findings also revealed that the mRNA and protein expression of FoxO1, MTP, and APOB in the liver was significantly down-regulated after the intervention of high-dose ZGJTQG(P<0.05, P<0.01). The above study showed that ZGJTQG could effectively improve glucolipid metabolism in T2DM combined with NAFLD, and the mechanism was closely related to the regulation of the FoxO1/MTP/APOB signaling pathway.


Subject(s)
Mice , Animals , Non-alcoholic Fatty Liver Disease/metabolism , Diabetes Mellitus, Type 2/metabolism , Liver , Lipoproteins, LDL/metabolism , Signal Transduction , Diet, High-Fat/adverse effects , RNA, Messenger/metabolism
11.
Chinese Journal of Natural Medicines (English Ed.) ; (6): 411-422, 2023.
Article in English | WPRIM | ID: wpr-982712

ABSTRACT

Alkaloids are a class of naturally occurring bioactive compounds that are widely distributed in various food sources and Traditional Chinese Medicine. This study aimed to investigate the therapeutic effects and underlying mechanisms of alkaloid extract from Codonopsis Radix (ACR) in ameliorating hepatic lipid accumulation in a mouse model of non-alcoholic fatty liver disease (NAFLD) induced by a high-fat diet (HFD). The results revealed that ACR treatment effectively mitigated the abnormal weight gain and hepatic injury associated with HFD. Furthermore, ACR ameliorated the dysregulated lipid metabolism in NAFLD mice, as evidenced by reductions in serum triglyceride, total cholesterol, and low-density lipoprotein levels, accompanied by a concomitant increase in the high-density lipoprotein level. ACR treatment also demonstrated a profound anti-oxidative effect, effectively alleviating HFD-induced oxidative stress and promoting ATP production. These effects were achieved through the up-regulation of the activities of mitochondrial electron transfer chain complexes I, II, IV, and V, in addition to the activation of the AMPK/PGC-1α pathway, suggesting that ACR exhibits therapeutic potential in alleviating the HFD-induced dysregulation of mitochondrial energy metabolism. Moreover, ACR administration mitigated HFD-induced endoplasmic reticulum (ER) stress and suppressed the overexpression of ubiquitin-specific protease 14 (USP14) in NAFLD mice. In summary, the present study provides compelling evidence supporting the hepatoprotective role of ACR in alleviating lipid deposition in NAFLD by improving energy metabolism and reducing oxidative stress and ER stress. These findings warrant further investigation and merit the development of ACR as a potential therapeutic agent for NAFLD.


Subject(s)
Mice , Animals , Non-alcoholic Fatty Liver Disease/metabolism , Codonopsis , Liver , Lipid Metabolism , Antineoplastic Agents/pharmacology , Alkaloids/pharmacology , Endoplasmic Reticulum Stress , Energy Metabolism , Lipids , Diet, High-Fat/adverse effects , Mice, Inbred C57BL
12.
Journal of Zhejiang University. Science. B ; (12): 587-601, 2023.
Article in English | WPRIM | ID: wpr-982402

ABSTRACT

Studies have shown that targeting xanthine oxidase (XO) can be a feasible treatment for fructose-induced hyperuricemia and hyperglycemia. This study aimed to evaluate the dual regulatory effects and molecular mechanisms of diacylated anthocyanins from purple sweet potato (diacylated AF-PSPs) on hyperglycemia and hyperuricemia induced by a high-fructose/high-fat diet. The body weight, organ index, serum biochemical indexes, and liver antioxidant indexes of mice were measured, and the kidneys were observed in pathological sections. The relative expression levels of messenger RNAs (mRNAs) of fructose metabolism pathway enzymes in kidney were detected by fluorescent real-time quantitative polymerase chain (qPCR) reaction technique, and the expression of renal transporter protein and inflammatory factor pathway protein was determined by immunohistochemistry (IHC) technique. Results showed that diacylated AF-PSPs alleviated hyperuricemia in mice, and that this effect might be related to the regulation of liver XO activity, lipid accumulation, and relevant renal transporters. Diacylated AF-PSPs reduced body weight and relieved lipid metabolism disorder, liver lipid accumulation, and liver oxidative stress, thereby enhancing insulin utilization and sensitivity, lowering blood sugar, and reducing hyperglycemia in mice. Also, diacylated AF-PSPs restored mRNA levels related to renal fructose metabolism, and reduced kidney injury and inflammation. This study provided experimental evidence for the mechanisms of dual regulation of blood glucose and uric acid (UA) by diacylated AF-PSPs and their utilization as functional foods in the management of metabolic syndrome.


Subject(s)
Mice , Animals , Hyperuricemia/drug therapy , Diet, High-Fat/adverse effects , Anthocyanins/chemistry , Ipomoea batatas/chemistry , Fructose/adverse effects , Hyperglycemia/drug therapy , Lipids
13.
São Paulo; s.n; s.n; 2023. 52 p. tab, graf, ilus.
Thesis in Portuguese | LILACS | ID: biblio-1437572

ABSTRACT

A obesidade está associada ao desenvolvimento de doenças crônicas não transmissíveis como hipertensão, resistência insulínica, dislipidemia e esteatose hepática. O consumo de compostos bioativos impacta na manutenção da saúde e na prevenção de risco de desenvolvimento dessas doenças. Entre os compostos bioativos, os monoterpenos são pouco investigados, apesar da literatura demonstrar efeitos promissores desses compostos sobre o metabolismo. O D-limoneno, o principal monoterpeno encontrado na laranja, é caracterizado por possuir efeitos hipolipemiantes, anti-inflamatórios e anti-obesogênicos. Estudos in vitro e in vivo descrevem sua capacidade de promover a ß-oxidação de ácidos graxos em adipócitos e redução da inflamação. Este estudo teve como objetivo investigar o efeito do D-limoneno no metabolismo e inflamação em um modelo de obesidade induzida por dieta. Para isso, quarenta camundongos machos (C57/Bl6) de 11 semanas de idade, foram distribuídos em 4 grupos, sendo que um dos grupos recebeu ração normolipídica e os demais, ração hiperlipídica. O D-limoneno foi suplementado na ração de dois grupos que receberam dieta hiperlipídica nas concentrações de 0,1%, e 0,8%. Considerando-se a ingestão alimentar dos animais, a ração suplementada com 0,1% D-limoneno correspondeu à ingestão de 0,15 g/kg/dia e ração com 0,8% de D-limoneno correspondeu a 1,3 g/kg/dia. Os animais tiveram o peso e a ingestão alimentar monitorados ao longo da intervenção com duração de 7 semanas. Os camundongos que receberam D-limoneno a 0,1% apresentaram menor ganho de peso e de acúmulo de tecido adiposo, comparado com os animais sem suplementação alimentados com a dieta hiperlipídica. Além disso, o D-limoneno promoveu a diminuição da concentração plasmática de marcadores inflamatórios incluindo TNF-α, INF-γ e IL-6 nos animais dos grupos que foram suplementados com D-limoneno. Entretanto, não houve diferença nos marcadores bioquímicos e metabólicos. Uma limitação do estudo foi o fato das complicações metabólicas associadas ao modelo de obesidade não terem sido plenamente estabelecidas, dados o alojamento individual, à curta duração da exposição à ração hiperlipídica e idade dos animais no início da suplementação. Esse fato pode ter dificultado a observação dos efeitos do D-limoneno na reversão dos parâmetros que seriam normalmente deteriorados pelo desenvolvimento da obesidade. Concluímos que o D-limoneno pode interferir no metabolismo energético, com possível efeito anti-obesogênico e anti-inflamatório. Devido às limitações do modelo, são necessários mais estudos para confirmar esses resultados


Obesity is associated with the development of chronic non-communicable diseases such as hypertension, insulin resistance, dyslipidemia, and hepatic steatosis. The intake of dietary bioactive compounds is associated with the maintenance of health and the prevention of chronic diseases. Among the group of bioactive compounds, monoterpenes are poorly investigated, in spite of several reports of their promising effects on metabolism. D-limonene is the main monoterpene found in oranges, known for its hypolipemic, anti-inflammatory, and anti-obesogenic effects. in vitro and in vivo studies associate D-limonene to increased ß-oxidation of fatty acids in adipocytes and reduced inflammation. This study aimed at investigating the effects of D-limonene on metabolism and inflammation in a diet-induced obesity model. For this purpose, forty male mice (C57/Bl6) were distributed in 4 groups, with one group receiving a normolipidic diet and the others, a high-fat diet. D-limonene was supplemented in the diets of two groups that received high-fat diet at the concentrations of 0.1% and 0.8%. Considering the feed intake, mice receiving D-limonene supplementation at 0.1% ingested in average 0.15 g/kg/day, while the mice receiving the supplemmentation at 0.8%, ingested approximately 1.3 g of D-limonene /kg/day. The animals had their weight and food intake monitored throughout the intervention. Mice that received Dlimonene supplementation at 0.1% showed reduced weight gain and accumulation of adipose tissue compared to the non-supplemented mice fed the high-fat diet. In addition, D-limonene promoted a decrease in hepatic inflammatory markers including TNF-α, INF-γ, and IL-6. However, there was no difference in biochemical and metabolic markers. A limitation of the study was that the metabolic complications associated with the obesity model were not fully established, probably due to the age at the start of the protocol (11 weeks), individual housing and short duration of the exposure to the high-fat feed. This fact may have prevented the observation of the positive effects of D-limonene in reversing parameters that would normally be impaired by the development of obesity. We conclude that D-limonene may interfere in energy metabolism, with a possible anti-obesogenic and anti-inflammatory effect. Due to the limitations of the model, further studies are needed to confirm these findings


Subject(s)
Animals , Male , Mice , Limonene/adverse effects , Obesity/chemically induced , In Vitro Techniques/methods , Chronic Disease/classification , Citrus sinensis/metabolism , Monoterpenes/analysis , Diet, High-Fat/adverse effects , Inflammation/complications , Anti-Inflammatory Agents/administration & dosage
14.
Braz. j. biol ; 83: e242818, 2023. tab, graf
Article in English | LILACS, VETINDEX | ID: biblio-1285628

ABSTRACT

Abstract The study was aimed to assess impact of high fat diet (HFD) and synthetic human gut microbiota (GM) combined with HFD and chow diet (CD) in inducing type-2 diabetes (T2D) using mice model. To our knowledge, this is the first study using selected human GM transplantation via culture based method coupled dietary modulation in mice for in vivo establishment of inflammation leading to T2D and gut dysbiosis. Twenty bacteria (T2D1-T2D20) from stool samples of confirmed T2D subjects were found to be morphologically different and subjected to purification on different media both aerobically and anerobically, which revealed seven bacteria more common among 20 isolates on the basis of biochemical characterization. On the basis of 16S rRNA gene sequencing, these seven isolates were identified as Bacteroides stercoris (MT152636), Lactobacillus acidophilus (MT152637), Lactobacillus salivarius (MT152638), Ruminococcus bromii (MT152639), Klebsiella aerogenes (MT152640), Bacteroides fragilis (MT152909), Clostridium botulinum (MT152910). The seven isolates were subsequently used as synthetic gut microbiome (GM) for their role in inducing T2D in mice. Inbred strains of albino mice were divided into four groups and were fed with CD, HFD, GM+HFD and GM+CD. Mice receiving HFD and GM+modified diet (CD/HFD) showed highly significant (P<0.05) increase in weight and blood glucose concentration as well as elevated level of inflammatory cytokines (TNF-α, IL-6, and MCP-1) compared to mice receiving CD only. The 16S rRNA gene sequencing of 11 fecal bacteria obtained from three randomly selected animals from each group revealed gut dysbiosis in animals receiving GM. Bacterial strains including Bacteroides gallinarum (MT152630), Ruminococcus bromii (MT152631), Lactobacillus acidophilus (MT152632), Parabacteroides gordonii (MT152633), Prevotella copri (MT152634) and Lactobacillus gasseri (MT152635) were isolated from mice treated with GM+modified diet (HFD/CD) compared to strains Akkermansia muciniphila (MT152625), Bacteriodes sp. (MT152626), Bacteroides faecis (MT152627), Bacteroides vulgatus (MT152628), Lactobacillus plantarum (MT152629) which were isolated from mice receiving CD/HFD. In conclusion, these findings suggest that constitution of GM and diet plays significant role in inflammation leading to onset or/and possibly progression of T2D. .


Resumo O estudo teve como objetivo avaliar o impacto da dieta rica em gordura (HFD) e da microbiota intestinal humana sintética (GM) combinada com HFD e dieta alimentar (CD) na indução de diabetes tipo 2 (T2D) usando modelo de camundongos. Para nosso conhecimento, este é o primeiro estudo usando transplante de GM humano selecionado através do método baseado em cultura acoplada à modulação dietética em camundongos para o estabelecimento in vivo de inflamação que leva a T2D e disbiose intestinal. Vinte bactérias (T2D1-T2D20) de amostras de fezes de indivíduos T2D confirmados verificaram ser morfologicamente diferentes e foram submetidas à purificação em meios diferentes aerobicamente e anaerobicamente, o que revelou sete bactérias mais comuns entre 20 isolados com base na caracterização bioquímica. Com base no sequenciamento do gene 16S rRNA, esses sete isolados foram identificados como Bacteroides stercoris (MT152636), Lactobacillus acidophilus (MT152637), Lactobacillus salivarius (MT152638), Ruminococcus bromii (MT152639), Klebsiella aerogenides (MT152640), Bacteroides fragilis (MT152909), Clostridium botulinum (MT152910). Esses sete isolados foram, posteriormente, usados ​​como microbioma intestinal sintético (GM) por seu papel na indução de T2D em camundongos. Linhagens consanguíneas de camundongos albinos foram divididas em quatro grupos e foram alimentadas com CD, HFD, GM + HFD e GM + CD. Camundongos que receberam a dieta modificada com HFD e GM + (CD / HFD) mostraram um aumento altamente significativo (P < 0,05) no peso e na concentração de glicose no sangue, bem como um nível elevado de citocinas inflamatórias (TNF-α, IL-6 e MCP-1) em comparação com os ratos que receberam apenas CD. O sequenciamento do gene 16S rRNA de 11 bactérias fecais obtidas de três animais selecionados aleatoriamente de cada grupo revelou disbiose intestinal em animais que receberam GM. Cepas bacterianas, incluindo Bacteroides gallinarum (MT152630), Ruminococcus bromii (MT152631), Lactobacillus acidophilus (MT152632), Parabacteroides gordonii (MT152633), Prevotella copri (MT152634) e Lactobacillus Gasseri (MT152635D), foram tratadas com dieta modificada / CD) em comparação com as linhagens Akkermansia muciniphila (MT152625), Bacteriodes sp. (MT152626), Bacteroides faecis (MT152627), Bacteroides vulgatus (MT152628), Lactobacillus plantarum (MT152629), que foram isoladas de camundongos recebendo CD / HFD. Em conclusão, esses resultados sugerem que a constituição de GM e dieta desempenham papel significativo na inflamação levando ao início ou/e possivelmente à progressão de T2D.


Subject(s)
Humans , Animals , Rabbits , Diabetes Mellitus, Type 2 , Gastrointestinal Microbiome , Bacteroides , RNA, Ribosomal, 16S/genetics , Prevotella , Bacteroidetes , Ruminococcus , Diet, High-Fat/adverse effects , Dysbiosis , Inflammation , Mice, Inbred C57BL
15.
Braz. j. biol ; 82: 1-8, 2022. tab
Article in English | LILACS, VETINDEX | ID: biblio-1468423

ABSTRACT

Exposure to the hight-fat diet may alter the control of food intake promoting hyperphagia and obesity. The objective of this study was to investigate the effects of this diet on dopamine receptors (drd1 and drd2), proopiomelanocortin (pomc), neuropeptideY (npy) genes expression, and preference food in adult rats. Wistar female rats were fed a hight-fat or control diet during pregnancy and lactation. The offspring were allocated into groups: Lactation – Control (C) and High-fat (H). Post- weaning – Control Control (CC), offspring of mothers C, fed a control diet after weaning; Control Hight-fat (CH), offspring of mothers C, fed a hight-fat diet after weaning; Hight-fat Control (HC), offspring of mothers H, fed with control diet after weaning; and Hight-fat Hight-fat (HH), offspring of mothers H, fed a H diet after weaning. The groups CH and HH presented greater expression of drd1 in comparison to the CC. The drd2 of CH and HC presented higher gene expression than did CC. HH presented higher pomc expression in comparison to the other groups. HC also presented greater expression in comparison to CH. The npy of HH presented greater expression in relation to CH and HC. HH and HC have had a higher preference for a high-fat diet at 102º life’s day. The high-fat diet altered the gene expression of the drd1, drd2, pomc and npy, and influencing the food preference for high-fat diet.


A exposição à dieta hiperlipídica pode alterar o controle da ingestão de alimentos, promovendo hiperfagia e obesidade. O objetivo deste estudo foi investigar os efeitos dessa dieta sobre a expressão gênica dos receptores de dopamina (drd1 e drd2), da proopiomelanocortina (pomc) e neuropeptídeo Y (npy), e preferência alimentar em ratos adultos. Ratas Wistar foram alimentadas com uma dieta hiperlipídica ou controle durante a gestação e lactação. Os descendentes foram alocados em grupos: Lactação – Controle (C) e Hiperlipídica (H). Pós-desmame – Controle Controle (CC), descendentes das genitoras do grupo controle e alimentados com dieta controle após o desmame; Controle Hiperlipídica (CH), descendentes das genitoras do grupo controle e alimentados com dieta hiperlipídica após o desmame; Hiperlipídica Controle (HC), descendentes das genitoras do grupo hiperlipídica e alimentados com dieta controle após o desmame; Hiperlipídica Hiperlipídica (HH), descendentes das genitoras do grupo hiperlipídica e alimentados com dieta hiperlipídica após o desmame. Os grupos CH e HH apresentaram maior expressão de drd1 em comparação ao CC. O drd2 de CH e HC apresentou maior expressão gênica que o CC. HH apresentou maior expressão de pomc em comparação com os outros grupos. O HC também apresentou maior expressão de pomc em comparação ao CH. O npy do HH apresentou maior expressão em relação ao CH e HC. HH e HC tiveram uma preferência maior por uma dieta rica em gordura no 102º dia de vida. A dieta hiperlipídica alterou a expressão gênica dos drd1, drd2, pomc e npy e influenciou na preferência alimentar pela dieta hiperlipídica.


Subject(s)
Female , Animals , Rats , Diet, High-Fat/adverse effects , Diet, High-Fat/veterinary , Dopamine/analysis , Neuropeptide Y/analysis , Pro-Opiomelanocortin/analysis , Rats, Wistar
16.
Braz. j. biol ; 82: e247102, 2022. tab, graf
Article in English | LILACS, VETINDEX | ID: biblio-1278491

ABSTRACT

The current investigation was carried out to estimate the protective effect of aqueous extract of Cheatomorpha gracilis (AEC) against High fat Diet (HFD) induced liver damage in mice. The results of the in vitro study showed that AEC have higher antioxidant capacities in the DPPH and hydroxyl radical-scavenging assays. Indeed, many phenolic compounds (gallic acid, quercetin, naringenin, apigenin, kaempferol and rutin) were identified in the AEC. In the animal studies, during 6 weeks, HFD promoted oxidative stress with a rise level of malonaldehyde (MDA), protein carbonyls (PCOs) levels and a significant decrease of the antioxidant enzyme activities such as superoxide dismutase, catalase and glutathione peroxidase. Interestingly, the treatment with AEC (250 mg/kg body weight) significantly reduced the effects of HFD disorders on some plasmatic liver biomarkers (AST, ALT and ALP) in addition to, plasmatic proteins inflammatory biomarkers (α2 and ß1 decreases / ß2 and γ globulins increases). It can be suggest that supplementation of MECG displays high potential to quench free radicals and attenuates high fat diet promoted liver oxidative stress and related disturbances.


A presente investigação foi realizada para estimar o efeito protetor do extrato aquoso de Cheatomorpha gracilis (AEC) contra o dano hepático induzido por dieta rica em gordura (HFD) em camundongos. Os resultados do estudo in vitro mostraram que os AEC têm maiores capacidades antioxidantes nos ensaios DPPH e de eliminação de radicais hidroxila. De fato, muitos compostos fenólicos (ácido gálico, quercetina, naringenina, apigenina, kaempferol e rutina) foram identificados no AEC. Nos estudos em animais, durante 6 semanas, HFD promoveu estresse oxidativo com aumento do nível de malonaldeído (MDA), níveis de proteína carbonil (PCOs) e diminuição significativa das atividades de enzimas antioxidantes como superóxido dismutase, catalase e glutationa peroxidase. Curiosamente, o tratamento com AEC (250 mg / kg de peso corporal) reduziu significativamente os efeitos dos distúrbios de HFD em alguns biomarcadores hepáticos plasmáticos (AST, ALT e ALP), além de biomarcadores inflamatórios de proteínas plasmáticas (reduções α2 e ß1 / ß2 e γ aumenta as globulinas). Pode-se sugerir que a suplementação de MECG apresenta alto potencial para extinguir os radicais livres e atenua o estresse oxidativo do fígado promovido pela dieta rica em gordura e distúrbios relacionados.


Subject(s)
Animals , Rats , Plant Extracts/pharmacology , Diet, High-Fat/adverse effects , Chromatography, High Pressure Liquid , Oxidative Stress , Liver , Antioxidants/metabolism
17.
China Journal of Chinese Materia Medica ; (24): 2500-2508, 2022.
Article in Chinese | WPRIM | ID: wpr-928129

ABSTRACT

This study aimed to explore the effects of Gynostemma pentaphyllum saponins(GPs) on non-alcoholic fatty liver disease(NAFLD) induced by high-fat diet in rats and reveal the underlying mechanism. The NAFLD model rats were prepared with high-fat diet. Forty male Sprague Dawley(SD) rats were randomly assigned into the control group, model group, and low-, moderate-, and high-dose GPs(50, 100, and 150 mg·kg~(-1), respectively) groups. After intragastric administration for 8 continuous weeks, we determined the body weight, liver weight, the levels of total cholesterol(TC), triglyceride(TG), low-density lipoprotein cholesterol(LDL-c), high-density lipoprotein cholesterol(HDL-c), alanine aminotransferase(ALT), and aspartate aminotransferase(AST) in serum, and the levels of TC, TG, malondialdehyde(MDA), superoxide dismutase(SOD), catalase(CAT), and interleukin 6(IL-6) in the liver. Furthermore, we observed the pathological changes of liver tissue by oil red O staining and hematoxylin-eosin(HE) staining, sequenced the 16 S rRNA of the intestinal flora in rat feces, and determined the content of short-chain fatty acids in rat feces. The results showed that GPs inhibited the excessive weight gain of high-fat diet-induced NAFLD in rats, reduced the liver weight, lowered the TC, TG, LDL-c, AST, and ALT levels in serum(P<0.05), and rose the HDL-c level in serum(P<0.01). GPs relieved the liver damage caused by high-fat diet, mainly manifested by the lowered levels of TC, TG, MDA, and IL-6 in the liver(P<0.01) and elevated levels of CAT and SOD in the liver. Furthermore, GPs reversed the intestinal flora disorder caused by high-fat diet, restored the diversity of intestinal flora, increased the relative abundance of Bacteroides, and reduced the relative abundance of Firmicutes and the ratio of Firmicutes to Bacteroides. Moreover, GPs promoted the proliferation of beneficial bacteria such as Akkermansia, Bacteroides, and Parabacteroides, and inhibited the growth of harmful bacteria such as Desulfovibrio, Escherichia-Shigella, and Helicobacter. GPs increased the content of short-chain fatty acids(acetic acid, propionic acid, and butyric acid)(P<0.01). These findings indicate that GPs can alleviate the high-fat diet-induced NAFLD in rats via regulating the intestinal flora and short-chain fatty acid metabolism.


Subject(s)
Animals , Male , Rats , Alanine Transaminase/metabolism , Cholesterol, LDL/pharmacology , Diet, High-Fat/adverse effects , Gastrointestinal Microbiome , Gynostemma , Interleukin-6/metabolism , Liver , Non-alcoholic Fatty Liver Disease/metabolism , Rats, Sprague-Dawley , Saponins/pharmacology , Superoxide Dismutase/metabolism
18.
Chinese Journal of Applied Physiology ; (6): 47-52, 2022.
Article in Chinese | WPRIM | ID: wpr-927896

ABSTRACT

Objective: To investigate the effects of continuous exercise training (CT) and high-intensity interval exercise training (HIIT) on liver lipid metabolism and the correlation of the level of fibroblast growth factor 21(FGF21) in serum and liver tissues. Methods: Male SD rats were randomly divided into normal diet group (N) and obesity model group (H) after 1 week of adaptive feeding. Rats in the obesity model group were fed with 45% high-fat diet for about 8 weeks, and 20% weight increase compared with normal rats was considered as obesity. The rats were divided into normal diet control group (LC), normal diet HIIT group (LHI), normal diet CT group (LCT), High fat diet-induced obese control group (OC), obese HIIT group (OHI), and obese CT group (OCT) (n=10). Exercised rats were given weight-bearing swimming training intervention for 8 weeks. Blood samples were collected at least 24h after the last exercise intervention to detect the serum levels of inflammatory factors and FGF21. Liver tissue samples were collected to detect the lipid content, lipid metabolic enzyme content and FGF21 expression level. Results: Compared with LC group, the body weight, serum inflammatory factors levels and hepatic triglyceride content were increased significantly (P<0.05). Hepatic triglyceride content was downregulated in LHI group and FGF21 expression level was enhanced in LCT group (P<0.05). Compared with OC group, the body weight and hepatic triglyceride content were decreased significantly (P<0.05), mitochondrial CPT-1β and β-HAD enzyme contents in liver were increased significantly (P<0.05) in OHI group, the contents of LPL and FAT/CD36 enzyme in liver and the levels of FGF21 in serum and liver of OCT group were increased significantly (P<0.05). Conclusion: Both exercise modes can reduce the body weight in normal and obese rats, and lipid deposition in the liver of obese rats. HIIT has a more significant effect on alleviating liver lipid deposition in obese rats by upregulating mitochondrial lipid oxidation level in normal and obese rats. CT improves the levels of FGF21 in serum and liver tissues of normal and obese rats, enhances enzyme contents that involved in fatty acids uptake to the liver, which has limited effect on alleviating lipid deposition in liver of obese rats.


Subject(s)
Animals , Male , Rats , Body Weight , Diet, High-Fat/adverse effects , Fatty Liver , Fibroblast Growth Factors , Obesity/metabolism , Rats, Sprague-Dawley , Triglycerides
19.
São Paulo; s.n; s.n; 2022. 103 p. tab, graf.
Thesis in English | LILACS | ID: biblio-1397316

ABSTRACT

The inverse relationship between HDL-C (high-density lipoprotein cholesterol) and cardiovascular disease is well established. However, it is consensus that the cholesterol content present in HDL does not capture its complexity, and other metrics need to be explored. HDL is a heterogeneous, protein-enriched particle with functions going beyond lipid metabolism. In this way, its protein content seems to be attractive to investigate its behavior in the face of pathologies. Many of the proteins with important function in HDL are in low abundance (<1% of total proteins), which makes their detection challenging. Quantitative proteomics allows detecting proteins with high precision and robustness in complex matrix. However, quantitative proteomics is still poorly explored in the context of HDL. In this sense, in the second chapter of this thesis, the analytical performance of two quantitative methodologies was carefully investigated. These methods achieved adequate linearity and high precision using labeled peptides in a pool HDL, in addition to comparable ability to differentiate proteins from HDL subclasses of healthy subjects. Another bottleneck that waits for a solution in proteomics is the lack of standardization in data processing and analysis after mass spectrometry acquisition. In addition, interest in the cardioprotective properties of omega-3 is growing, but little is known about its effects on the HDL proteome. Thus, in the third chapter of this thesis, we compared five protein quantification strategies using Skyline and MaxDIA software platforms in order to investigate the HDL proteome from mice submitted to a high-fat diet supplemented or not with omega-3. MaxDIA with label-free quantification (MaxLFQ) achieved high precision to show that polyunsaturated fatty acids remodel the HDL proteome to a less inflammatory profile. Therefore, the two studies presented in this thesis begin to open new paths for a deeper and more reliable understanding of HDL, both at the level of protein quantification by mass spectrometry and after data acquisition


A inversa relação entre HDL-C (do inglês, high-density lipoprotein cholesterol) e doenças cardiovasculares é bem estabelecida. No entanto, é consenso que o conteúdo de colesterol presente na HDL não captura sua complexidade, e outras métricas precisam ser exploradas. A HDL é uma partícula heterogênea, enriquecida em proteínas, com funções que vão além do metabolismo de lipídeos. Dessa forma, seu conteúdo proteico parece ser mais atrativo para exprimir seu comportamento frente às patologias. Muitas das proteínas com função importante estão em baixa abundância (<1% do total de proteínas), o que torna a detecção desafiadora. Métodos quantitativos de proteômica permitem detectar proteínas com alta precisão e robustez em matrizes complexas. No entanto, a proteômica quantitativa ainda é pouco explorada no contexto da HDL. Nesse sentido, no segundo capítulo dessa tese, a performance analítica de dois métodos quantitativos foi criteriosamente investigada, os quais alcançaram adequada linearidade e alta precisão usando peptídeos marcados em um pool de HDL, além de comparável habilidade em diferenciar as proteínas das subclasses da HDL de indivíduos saudáveis. Outro gargalo que aguarda por solução em proteômica é a falta de padronização no processamento e análise de dados após a aquisição por espectrometria de massas. Além disso, é crescente o interesse das propriedades cardioprotetivas do ômega-3, porém pouco se conhece sobre seus efeitos no proteoma da HDL. Então, no terceiro capítulo dessa tese, comparamos cinco estratégias de quantificação de proteínas utilizando os softwares Skyline e MaxDIA com o intuito de comparar o proteoma da HDL de camundongos submetidos a uma dieta hiperlipídica suplementados ou não com ômega-3. MaxDIA com quantificação label-free (MaxLFQ) apresentou alta precisão para mostrar que o ômega-3 remodela o proteoma da HDL para um perfil menos inflamatório. Portanto, os dois estudos apresentados nessa tesa começam a abrir novos caminhos para o entendimento mais profundo e confiável da HDL tanto por meio da quantificação das proteínas por espectrometria de massas quanto após à aquisição dos dados


Subject(s)
Proteomics/instrumentation , Hyperlipidemias/pathology , Cholesterol, HDL/analysis , Mass Spectrometry/methods , Cardiovascular Diseases/pathology , Diet/classification , Diet, High-Fat/adverse effects
20.
Braz. j. biol ; 82: e234855, 2022. tab, graf
Article in English | LILACS, VETINDEX | ID: biblio-1153468

ABSTRACT

Exposure to the hight-fat diet may alter the control of food intake promoting hyperphagia and obesity. The objective of this study was to investigate the effects of this diet on dopamine receptors (drd1 and drd2), proopiomelanocortin (pomc), neuropeptideY (npy) genes expression, and preference food in adult rats. Wistar female rats were fed a hight-fat or control diet during pregnancy and lactation. The offspring were allocated into groups: Lactation - Control (C) and High-fat (H). Post-weaning ­ Control Control (CC), offspring of mothers C, fed a control diet after weaning; Control Hight-fat (CH), offspring of mothers C, fed a hight-fat diet after weaning; Hight-fat Control (HC), offspring of mothers H, fed with control diet after weaning; and Hight-fat Hight-fat (HH), offspring of mothers H, fed a H diet after weaning. The groups CH and HH presented greater expression of drd1 in comparison to the CC. The drd2 of CH and HC presented higher gene expression than did CC. HH presented higher pomc expression in comparison to the other groups. HC also presented greater expression in comparison to CH. The npy of HH presented greater expression in relation to CH and HC. HH and HC have had a higher preference for a high-fat diet at 102º life's day. The high-fat diet altered the gene expression of the drd1, drd2, pomc and npy, and influencing the food preference for high-fat diet.


A exposição à dieta hiperlipídica pode alterar o controle da ingestão de alimentos, promovendo hiperfagia e obesidade. O objetivo deste estudo foi investigar os efeitos dessa dieta sobre a expressão gênica dos receptores de dopamina (drd1 e drd2), da proopiomelanocortina (pomc) e neuropeptídeo Y (npy), e preferência alimentar em ratos adultos. Ratas Wistar foram alimentadas com uma dieta hiperlipídica ou controle durante a gestação e lactação. Os descendentes foram alocados em grupos: Lactação ­ Controle (C) e Hiperlipídica (H). Pós-desmame - Controle Controle (CC), descendentes das genitoras do grupo controle e alimentados com dieta controle após o desmame; Controle Hiperlipídica (CH), descendentes das genitoras do grupo controle e alimentados com dieta hiperlipídica após o desmame; Hiperlipídica Controle (HC), descendentes das genitoras do grupo hiperlipídica e alimentados com dieta controle após o desmame; Hiperlipídica Hiperlipídica (HH), descendentes das genitoras do grupo hiperlipídica e alimentados com dieta hiperlipídica após o desmame. Os grupos CH e HH apresentaram maior expressão de drd1 em comparação ao CC. O drd2 de CH e HC apresentou maior expressão gênica que o CC. HH apresentou maior expressão de pomc em comparação com os outros grupos. O HC também apresentou maior expressão de pomc em comparação ao CH. O npy do HH apresentou maior expressão em relação ao CH e HC. HH e HC tiveram uma preferência maior por uma dieta rica em gordura no 102º dia de vida. A dieta hiperlipídica alterou a expressão gênica dos drd1, drd2, pomc e npy e influenciou na preferência alimentar pela dieta hiperlipídica.


Subject(s)
Animals , Female , Pregnancy , Rats , Pro-Opiomelanocortin/genetics , Diet, High-Fat/adverse effects , Body Weight , Neuropeptide Y/genetics , Gene Expression , Receptors, Dopamine/genetics , Rats, Wistar , Food Preferences
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