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1.
Acta Physiologica Sinica ; (6): 439-450, 2023.
Article in Chinese | WPRIM | ID: wpr-981019

ABSTRACT

Lipid metabolism is a complex physiological process, which is closely related to nutrient regulation, hormone balance and endocrine function. It involves the interactions of multiple factors and signal transduction pathways. Lipid metabolism disorder is one of the main mechanisms to induce a variety of diseases, such as obesity, diabetes, non-alcoholic fatty liver disease, hepatitis, hepatocellular carcinoma and their complications. At present, more and more studies have found that the "dynamic modification" of N6-adenylate methylation (m6A) on RNA represents a new "post-transcriptional" regulation mode. m6A methylation modification can occur in mRNA, tRNA, ncRNA, etc. Its abnormal modification can regulate gene expression changes and alternative splicing events. Many latest references have reported that m6A RNA modification is involved in the epigenetic regulation of lipid metabolism disorder. Based on the major diseases induced by lipid metabolism disorders, we reviewed the regulatory roles of m6A modification in the occurrence and development of those diseases. These overall findings inform further in-depth investigations of the underlying molecular mechanisms regarding the pathogenesis of lipid metabolism disorders from the perspective of epigenetics, and provide reference for health prevention, molecular diagnosis and treatment of related diseases.


Subject(s)
Humans , Methylation , Epigenesis, Genetic , Lipid Metabolism/genetics , Lipid Metabolism Disorders/genetics , Liver Neoplasms , RNA
2.
Article in Chinese | WPRIM | ID: wpr-981525

ABSTRACT

Through the non-targeted metabolomics study of endogenous substances in the liver and serum of hyperlipidemia rats, the biomarkers related to abnormal lipid metabolism in hyperlipidemia rats were found, and the target of ginsenoside Rb_1 in improving hyperlipidemia was explored and its mechanism was elucidated. The content of serum biochemical indexes of rats in each group was detected by the automatic biochemical analyzer. The metabolite profiles of liver tissues and serum of rats were analyzed by HPLC-MS. Principal component analysis(PCA) and orthogonal partial least squares-discriminant analysis(OPLS-DA) were used to compare and analyze the metabolic data in the normal group, the hyperlipidemia group, and the ginsenoside Rb_1 group, and screen potential biomar-kers. The related metabolic pathways were further constructed by KEGG database analysis. The results showed that hyperlipemia induced dyslipidemia in rats, which was alleviated by ginsenoside Rb_1. The non-targeted metabolomics results showed that there were 297 differential metabolites in the liver tissues of hyperlipidemia rats, 294 differential metabolites in the serum samples, and 560 diffe-rential metabolites in the hyperlipidemia rats treated by ginsenoside Rb_1. Perillic acid and N-ornithyl-L-taurine were common metabolites in the liver and serum samples, which could be used as potential biomarkers for ginsenoside Rb_1 in the improvement of hyperlipidemia. As revealed by pathway enrichment in the liver and serum, ginsenoside Rb_1 could participate in the metabolic pathway of choline in both the liver and serum. In addition, ginsenoside Rb_1 also participated in the ABC transporter, alanine, aspartic acid, and glutamate metabolism, protein digestion and absorption, β-alanine metabolism, taurine and hypotaurine metabolism, caffeine metabolism, valine, leucine, and isoleucine biosynthesis, arachidonic acid metabolism, and methionine and cysteine metabolism to improve dyslipidemia in rats.


Subject(s)
Rats , Animals , Hyperlipidemias/drug therapy , Metabolome , Ginsenosides/metabolism , Lipid Metabolism , Metabolomics/methods , Liver/metabolism , Biomarkers , Taurine
3.
Article in Chinese | WPRIM | ID: wpr-981459

ABSTRACT

This study aims to investigate the efficacy and possible mechanism of Liuwei Dihuang Pills in the treatment of diminished ovarian reserve(DOR) by using proteomic techniques. Firstly, cyclophosphamide(60 mg·kg~(-1)) combined with busulfan(6 mg·kg~(-1)) was injected intraperitoneally to establish the mouse model of DOR. After drug injection, the mice were continuously observed and the success of modeling was evaluated by the disturbance of the estrous cycle. After successful modeling, the mice were administrated with the suspension of Liuwei Dihuang Pills by gavage for 28 days. At the end of the gavage, four female mice were selected and caged together with males at a ratio of 2∶1 for the determination of the pregnancy rate. Blood and ovary samples were collected from the remaining mice on the next day after the end of gavage. Hematoxylin-eosin(HE) staining and transmission electron microscopy(TEM) were then employed to observe the morphological and ultrastructural changes in the ovaries. The serum levels of hormones and oxidation indicators were measured by enzyme-linked immunosorbent assay. Quantitative proteomics techniques were used to compare the ovarian protein expression before and after modeling and before and after the intervention with Liuwei Dihuang Pills. The results showed that Liuwei Dihuang Pills regulated the estrous cycle of DOR mice, elevated the serum levels of hormones and anti-oxidation indicators, promoted follicle development, protected the mitochondrial morphology of ovarian granulosa cells, and increased the litter size and survival of DOR mice. Furthermore, Liuwei Dihuang Pills negatively regulated the expression of 12 differentially expressed proteins associated with DOR, which were mainly involved in lipid catabolism, inflammatory response, immune regulation, and coenzyme biosynthesis. These differentially expressed proteins were significantly enriched in sphingolipid metabolism, arachidonic acid metabolism, ribosomes, ferroptosis, and cGMP-PKG signaling pathway. In summary, the occurrence of DOR and the treatment of DOR with Liuwei Dihuang Pills are associated with multiple biological pathways, mainly including oxidative stress response, inflammatory response, and immune regulation. "Mitochondria-oxidative stress-apoptosis" is the key to the treatment of DOR by Liuwei Dihuang Pills. YY1 and CYP4F3 may be the key upstream targets that trigger mitochondrial dysfunction and ROS accumulation, and the metabolism of arachidonic acid is the main signaling pathway of drug action.


Subject(s)
Female , Male , Pregnancy , Animals , Mice , Arachidonic Acid , Ovarian Reserve , Proteomics , Ovary , Lipid Metabolism
4.
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.
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.
Article in Chinese | WPRIM | ID: wpr-970635

ABSTRACT

With the improvement of living standards and changes in working style, the prevalence of abnormal glucose and lipid metabolism in humans is increasing in modern society. Clinically, the related indicators are often improved by changing the lifestyle and/or taking hypoglycemic and lipid-lowering drugs, but there are no therapeutic drugs for disorders of glucose and lipid metabolism at present. Hepatitis C virus core protein binding protein 6(HCBP6) is a newly discovered target that can regulate triglyceride and cholesterol content according to level oscillations in the body, thereby regulating abnormal glucose and lipid metabolism. Relevant studies have shown that ginsenoside Rh_2 can significantly up-regulate the expression of HCBP6, but there are few studies on the effect of Chinese herbal medicines on HCBP6. Moreover, the three-dimensional structural information of HCBP6 has not been determined and the discovery of potential active components acting on HCBP6 is not rapidly advanced. Therefore, the total saponins of eight Chinese herbal medicines commonly used to regulate abnormal glucose and lipid metabolism were selected as the research objects to observe their effect on the expression of HCBP6. Then, the three-dimensional structure of HCBP6 was predicted, followed by molecular docking with saponins in eight Chinese herbal medicines to quickly find potential active components. The results showed that all total saponins tended to up-regulate HCBP6 mRNA and protein expression, where gypenosides showed the optimum effect on up-regulating HCBP6 mRNA and ginsenosides showed the optimum effect on up-regulating HCBP6 protein expression. Reliable protein structures were obtained after the prediction of protein structures using the Robetta website and the evaluation of the predicted structures by SAVES. The saponins from the website and literature were also collected and docked with the predicted protein, and the saponin components were found to have good binding activity to the HCBP6 protein. The results of the study are expected to provide ideas and methods for the discovery of new drugs from Chinese herbal medicines to regulate glucose and lipid metabolism.


Subject(s)
Humans , Glucose , Lipid Metabolism , Molecular Docking Simulation , Drugs, Chinese Herbal/pharmacology , Ginsenosides , Proteins , Saponins , RNA, Messenger
7.
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
8.
Article in English | WPRIM | ID: wpr-982320

ABSTRACT

OBJECTIVES@#Polycystic ovary syndrome (PCOS) is one of the most common endocrine diseases in women with reproductive age, which is associated with hyperandrogenism, insulin resistance, and ovulatory dysfunction. Progesterone receptor membrane component 1 (PGRMC1) can mediate progesterone to inhibit the apoptosis of ovarian granulosa cells and the growth of follicles, and to induce glucolipid metabolism disorder in ovarian granulosa cells, which is closely related to the occurrence and development of PCOS. This study aims to determine the expression of PGRMC1 in serum, ovarian tissue, ovarian granulosa cells, and follicular fluid in PCOS patients and non-PCOS patients, analyze the value of PGRMC1 in diagnosis and prognosis evaluation of PCOS, and investigate its molecular mechanism on ovarian granulosa cell apoptosis and glucolipid metabolism.@*METHODS@#A total of 123 patients were collected from the Department of Obstetrics and Gynecology in Guangdong Women and Children Hospital (hereinafter referred to as "our hospital") from August 2021 to March 2022 and divided into 3 groups: a PCOS pre-treatment group (n=42), a PCOS treatment group (n=36), and a control group (n=45). The level of PGRMC1 in serum was detected by enzyme linked immunosorbent assay (ELISA). The diagnostic and prognostic value of PGRMC1 was evaluated in patients with PCOS by receiver operating characteristic (ROC) curve. Sixty patients who underwent a laparoscopic surgery from the Department of Obstetrics and Gynecology in our hospital from January 2014 to December 2016 were collected and divided into a PCOS group and a control group (n=30). The expression and distribution of PGRMC1 protein in ovarian tissues were detected by immunohistochemical staining. Twenty-two patients were collected from Reproductive Medicine Center in our hospital from December 2020 to March 2021, and they divided into a PCOS group and a control group (n=11). ELISA was used to detect the level of PGRMC1 in follicular fluid; real-time RT-PCR was used to detect the expression level of PGRMC1 mRNA in ovarian granulosa cells. Human ovarian granular cell line KGN cells were divided into a scrambled group which was transfected with small interfering RNA (siRNA) without interference and a siPGRMC1 group which was transfected with specific siRNA targeting PGRMC1. The apoptotic rate of KGN cells was detected by flow cytometry. The mRNA expression levels of PGRMC1, insulin receptor (INSR), glucose transporter 4 (GLUT4), very low density lipoprotein receptor (VLDLR), and low density lipoprotein receptor (LDLR) were determined by real-time RT-PCR.@*RESULTS@#The serum level of PGRMC1 in the PCOS pre-treatment group was significantly higher than that in the control group (P<0.001), and the serum level of PGRMC1 in the PCOS treatment group was significantly lower than that in the PCOS pre-treatment group (P<0.001). The areas under curve (AUC) of PGRMC1 for the diagnosing and prognosis evaluation of PCOS were 0.923 and 0.893, respectively, and the cut-off values were 620.32 and 814.70 pg/mL, respectively. The positive staining was observed on both ovarian granulosa cells and ovarian stroma, which the staining was deepest in the ovarian granulosa cells. The average optical density of PGRMC1 in the PCOS group was significantly increased in ovarian tissue and ovarian granulosa cells than that in the control group (both P<0.05). Compared with the control group, the PGRMC1 expression levels in ovarian granulosa cells and follicular fluid in the PCOS group were significantly up-regulated (P<0.001 and P<0.01, respectively). Compared with the scrambled group, the apoptotic rate of ovarian granulosa cells was significantly increased in the siPGRMC1 group (P<0.01), the mRNA expression levels of PGRMC1 and INSR in the siPGRMC1 group were significantly down-regulated (P<0.001 and P<0.05, respectively), and the mRNA expression levels of GLUT4, VLDLR and LDLR were significantly up-regulated (all P<0.05).@*CONCLUSIONS@#Serum level of PGRMC1 is increased in PCOS patients, and decreased after standard treatment. PGRMC1 could be used as molecular marker for diagnosis and prognosis evaluation of PCOS. PGRMC1 mainly localizes in ovarian granulosa cells and might play a key role in regulating ovarian granulosa cell apoptosis and glycolipid metabolism.


Subject(s)
Child , Pregnancy , Humans , Female , Polycystic Ovary Syndrome , Apoptosis , Granulosa Cells , Lipid Metabolism , Membrane Proteins , Receptors, Progesterone
9.
Acta sci., Biol. sci ; 45: e59835, 2023. tab, graf
Article in English | LILACS, VETINDEX | ID: biblio-1419132

ABSTRACT

We compared the effect of the treatment with strength training (ST) and raloxifene (RALOX) on bone weight, blood glucose, lipid, and antioxidant profile in ovariectomized rats. Twenty-four Wistar rats were distributed into four groups: ovariectomy + VEHICLE (control); ovariectomy + RALOX; ovariectomy + ST; ovariectomy + RALOX + ST. Thirty days after ovariectomy, the animals underwent the treatment with RALOX (750 µcg day-1) and/or ST (three sessions week-1). Thirty days after, all groups were scarified, tibia and femur were weighed, and the blood was collected for analysis of the lipid profile, glucose, and antioxidants catalase (CAT) and glutathione (GSH). The ST group showed greater femur weight (0.82 ± 0.18 g) and RALOX + ST had greater tibia weight (0.61± 0.17 g) than CONTROL with femur weight of 0.65 ± 0.08 g and tibia of 0.49 ± 0.08 g with no differences between treatments (p > 0.05). ST group showed significantly higher catalase (181.7 ± 15.4 µM g-1) compared to the other groups. In contrast, the GSH value was lower in ST group (89.2 ± 8.1 µM g-1) compared to RALOX (175.9 ± 17.1 µM g-1) and RALOX + ST (162.8 ± 12.1 µM g-1), but the values of these two groups did not differ from CONTROL(115.3 ± 21.1 µM g-1). Total cholesterol did not differ between groups (p > 0.05), but exercise alone(54.3 ± 2.5 mg dL-1) or with RALOX (53.0 ± 1.5 mg dL-1) resulted in higher HDL cholesterol than CONTROL (45.5 ± 2.5 mg dL-1). Only RALOX+ST presented lower glucose (140.3 ± 9.7 mg dL-1) values than CONTROL (201.7 ± 30.6 mg dL-1). In conclusion, ST promotes similar benefits on bone and metabolic parameters compared to pharmacological treatment in ovariectomized rats.(AU)


Subject(s)
Animals , Female , Rats, Wistar/physiology , Raloxifene Hydrochloride/adverse effects , Resistance Training/adverse effects , Blood Glucose/analysis , Ovariectomy/veterinary , Lipid Metabolism , Antioxidants
10.
São Paulo; s.n; 2023. 107 p.
Thesis in Portuguese | LILACS | ID: biblio-1513206

ABSTRACT

Introdução: A doença hepática gordurosa não alcoólica (DHGNA) caracteriza-se pelo acúmulo de triglicerídeos (TG) nos hepatócitos, destacando-se a elevada prevalência de esteatose hepática (NAFL). A NAFL é uma condição clínica definida pelo acúmulo de ácidos graxos (AG) no fígado, obtidos pela ingestão direta de gorduras e carboidratos e/ou pela síntese de AG via ativação da lipogênese. A NAFL é desencadeada por um conjunto de fatores, como o padrão dietético, o estilo de vida e a genética. Dietas hipercalóricas, caracterizadas pela presença de gorduras saturadas e carboidratos simples exercem importante papel no desenvolvimento da NAFL. Além disso, uma dieta rica em carboidratos simples, destacando-se a frutose, também é importante no NAFL, visto que a frutose, ao ser ingerida, é, majoritariamente, metabolizada pelo fígado, sendo assim, um componente mais sensível à lipogênese. Objetivo: Avaliar o impacto do consumo excessivo de frutose e lipídeos na modulação da inflamação e no metabolismo lipídico hepático. Metodologia: O estudo foi baseado em modelo experimental com 100 dias de seguimento. Dezoito ratos da espécie Wistar, machos e adultos jovens (7 semanas) foram distribuídos em 3 grupos: Dieta Controle (DC) (n=6) - ração comercial e água filtrada; Dieta Frutose (DF) (n=6) - ração comercial e água filtrada com 30% de frutose; e Dieta Hiperlipídica (DH) (n=6) - ração hiperlipídica e água filtrada. Ração e água foram administradas ad libitum. Após a eutanásia, o sangue e o fígado foram coletados. Resultados: Os animais do grupo DH tiveram um consumo de ração menor, assim como os animais do grupo DF, porém esses apresentaram um consumo calórico maior comparado ao grupo DC. Por outro lado, o aumento do comprimento foi significativo para todos, tendo o grupo DH apresentado maior crescimento. Conforme esperado, a cetose plasmática foi maior no grupo DH, assim como as enzimas hepáticas aspartato aminotransferase (AST), alanina aminotransferase (ALT) e fosfatase alcalina (FA). Glicose e frutose plasmáticas foram similares entre os grupos. O peso relativo do fígado foi maior no grupo DF comparado ao grupo DH. O conteúdo de colesterol total (CT), TG e ácidos graxos não esterificados (AGNE) foi superior no grupo que recebeu DH. Inesperadamente, as substâncias reativas ao ácido tiobarbitúrico (TBARS) foram superiores no grupo DC. Em relação a fosfolipase 3 associada à patatina (PNPLA3) observamos aumento expressivo no grupo DF comparado aos animais alimentados com DH, porém, os grupos foram semelhantes em relação ao fator de crescimento de fibroblasto 21 (FGF21) e ao membro 2 da superfamília da proteína trnasmembrana 6 (TM6SF2). As citocinas - interleucinas I-beta (IL-1ß), 6 (IL-6), 10 (IL-10) e fator de necrose tumoral (TNF-α) foram maiores no grupo DF. Na análise da histologia do tecido hepático observou-se a presença de infiltrado inflamatório acentuado e de esteatose hepática no grupo DH. Conclusão: Frutose (30%) e lipídios (90%), quando consumidos de forma crônica (100 dias) promovem inflamação e acúmulo de lipídios hepático compatíveis com a DHGNA.


Introduction: Non-alcoholic fatty liver disease (NAFLD) is characterized by the triglycerides (TG) accumulation in hepatocytes, highlighting the high prevalence of hepatic steatosis (NAFL). NAFL is a clinical condition defined by liver fatty acids (FA) accumulation, obtained by direct ingestion of fats and carbohydrates and/or by FA synthesis via lipogenesis activation. NAFL is triggered by a number of factors, such as dietary pattern, lifestyle and genetics. Hypercaloric diets, characterized by the presence of saturated fats and simple carbohydrates, play an important role in the development of NAFL. In addition, a diet rich in simple carbohydrates, especially fructose, is also important in NAFL, since fructose, when ingested, is mostly metabolized by liver, thus being a component that is more sensitive to lipogenesis. Objective: To evaluate the impact of excessive consumption of fructose and lipids on the inflammation modulation and hepatic lipid metabolism. Methodology: The study was based on a 100 days follow-up experimental model. Eighteen Wistar rats, male and young adults (7 weeks old) were distributed into 3 groups: Control Diet (CD) (n=6) - commercial chow and filtered water; Fructose Diet (FD) (n=6) - commercial feed and filtered water with 30% fructose; and High-fat Diet (HFD) (n=6) - high-fat diet and filtered water. Chow and water were administered ad libitum. After euthanasia, blood and liver were collected. Results: HFD animals group had a lower feed intake, as well as the FD animals group, but these ones had a higher caloric intake compared to the CD group. On the other hand, the length increase was significant for all and the HFD group showed greater growth. As expected, plasma ketosis was higher in the DH group, as were liver enzymes aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (AP). Plasma glucose and fructose were similar between groups. Liver relative weight was higher in the DF group compared to the HFD group. Total cholesterol (TC), TG and non-esterified fatty acids (NEFA) content was higher in HFD group. Unexpectedly, thiobarbituric acid reactive substances (TBARS) were higher in CD group. Regarding patatin-associated phospholipase 3 (PNPLA3), we observed a significant increase in FD group compared to animals fed with HD, however, the groups were similar in relation to fibroblast growth factor 21 (FGF21) and member 2 of the protein superfamily transmembrane 6 (TM6SF2). Cytokines - interleukins I-beta (IL-1ß), 6 (IL-6), 10 (IL-10) and tumor necrosis factor (TNF-α) were higher in FD group. In the analysis of the hepatic tissue histology, the presence of accentuated inflammatory infiltrate and hepatic steatosis was observed in DH group. Conclusion: Fructose (30%) and lipids (90%), when consumed chronically (100 days) promote inflammation and hepatic lipids accumulation compatible with NAFLD.


Subject(s)
Diet , Lipid Metabolism , Fatty Liver , Diet, High-Fat , Fructose , Inflammation
11.
Article in Chinese | WPRIM | ID: wpr-935291

ABSTRACT

Objective: To analyze the effect of psychological suggestion combined with rational food restriction therapy on blood glucose, lipid metabolism and mental resilience in patients with diabetes. Methods: Patients with diabetes admitted to the Third Hospital of Nanchang from January 2020 to August 2020 were divided into the control group and the intervention group with randomized controlled and single blind methods. The control group was treated with routine dietary guidance and health education, and the intervention group was treated with psychological suggestion combined with rational diet therapy on the basis of the control group. Both groups were treated for 3 months. Blood glucose, lipid metabolism, mental resilience and quality of life were compared between the two groups at baseline and after 3-month intervention. Differences between groups and within groups were analyzed by t test and χ2 test. Results: 100 patients in the control group and 81 patients in the intervention group completed 3-month intervention. After 3-month intervention, the levels of glycosylated hemoglobin, fasting blood glucose, 2-hour postprandial blood glucose, low-density lipoprotein cholesterol and triglyceride in both groups were lower than those before intervention. The levels of these indicators in intervention group were lower than those in control group (P<0.05). However, the levels of high-density lipoprotein cholesterol and the scores of tenacity, self-reliance, optimism, role function, emotional function, social function, physical function and cognitive function in both groups were higher than those before intervention. These indicators in intervention group were higher than those in control group (P<0.05). Conclusion: Psychological suggestion combined with rational food restriction therapy could effectively improve the glucose and lipid metabolism, mental resilience, and quality of life among patients with diabetes.


Subject(s)
Humans , Blood Glucose/metabolism , Diabetes Mellitus, Type 2 , Lipid Metabolism , Quality of Life , Single-Blind Method
12.
Article in English | WPRIM | ID: wpr-929001

ABSTRACT

OBJECTIVES@#Perfluorooctanoic acid (PFOA) can cause lipid metabolism disorders in animal body and affect the lipolysis and synthesis of fatty acids. Peroxisome proliferators-activated receptor (PPAR) plays an extremely important role in this process. This study aims to explore the effects of PFOA on liver lipid metabolism disorders in Sprague Dewley (SD) rats and the expression of PPAR.@*METHODS@#A total of 40 male SD rats were randomly divided into 4 groups (n=10 in each group): a control group (ddH2O), a low-dose PFOA group [PFOA 1.25 mg/(kg·d)], a middle-dose PFOA group [PFOA 5.00 mg/(kg·d)], and a high-dose PFOA group [PFOA 20.00 mg/(kg·d)]. The rats were fed with normal diet, and PFOA exposure were performed by oral gavage for 14 days, and the rats were observed, weighted and recorded every day during the exposure. After the exposure, the blood was collected, and the livers were quickly stripped after the rats were killed. Part of the liver tissues were fixed in 4% paraformaldehyde for periodic acid-schiff (PAS) staining; the contents of HDLC, LDLC, TG, TC in serum and liver tissues, as well as the activities of their related enzymes were assayed; The expression levels of cyclic adenosine monophosphate-response element binding protein (Cbp), general control of amino acid synthesis 5-like 2 (Gcn5L2), peroxidation peroxisome proliferation factor activated receptor γ (PPAR), silent information regulator 1 (Sirt1) and human retinoid X receptor alpha 2 (Rxrα2) ) were detected by Western blotting.@*RESULTS@#After 14 days of PFOA exposure, the PAS staining positive particles in the cytoplasm and nucleus of SD rats in the medium and high dose groups were significantly reduced compared with the control group. The serum levels of LDLC and TC in the low-dose and middle-dose groups were significantly reduced compared with the control group (all P<0.05), while the high-dose group showed an increasing tendency, without siginificant difference (P>0.05), there was no significant difference in HDLC and TG (both P>0.05). The activities of alkaline phosphatase (AKP) and alanine aminotransferase (ALT) were increased significantly (both P<0.05) compared with control group; the ratio of ALT/aspartate aminotransferase (AST) in the high-dose group was increased significantly (P<0.05), there was no significant difference in LDH and TG (both P>0.05); the HDLC content in the liver tissues in the high-dose group was significantly reduced, compared with the control group (P<0.05); the TC contents in the liver tissues in the low, medium and high-dose groups were significantly increased (all P<0.05), there was no significant difference in LDLC and TG (both P>0.05); the AKP activity in the livers in the medium and high-dose groups was significantly increased (both P<0.05), there was no siginificant difference in LDH, ALT, and the ratio of ALT/AST (all P>0.05); the protein expression levels of Ppar γ, Cbp and Rxrα2 in the liver in the high dose groups were significantly down-regulated compared with the control group (all P<0.05), while the protein expression levels of Sirt1 were significantly up-regulated (all P<0.05).@*CONCLUSIONS@#PFOA exposure can cause lipid metabolism disorder and glycogen reduction in SD rat livers, which may be related to the activation of Sirt1 and inhibition of Ppar γ expression, leading to affecting the normal metabolism of fatty acids and promoting glycolysis.


Subject(s)
Animals , Male , Rats , Caprylates , Fatty Acids/pharmacology , Fluorocarbons , Lipid Metabolism , Lipid Metabolism Disorders/metabolism , Liver/metabolism , PPAR gamma , Rats, Sprague-Dawley , Sirtuin 1/metabolism
13.
Neuroscience Bulletin ; (6): 809-819, 2022.
Article in English | WPRIM | ID: wpr-939834

ABSTRACT

Alzheimer's disease (AD) is the most prevalent neurodegenerative disease featuring progressive cognitive impairment. Although the etiology of late-onset AD remains unclear, the close association of AD with apolipoprotein E (APOE), a gene that mainly regulates lipid metabolism, has been firmly established and may shed light on the exploration of AD pathogenesis and therapy. However, various confounding factors interfere with the APOE-related AD risk, raising questions about our comprehension of the clinical findings concerning APOE. In this review, we summarize the most debated factors interacting with the APOE genotype and AD pathogenesis, depict the extent to which these factors relate to APOE-dependent AD risk, and discuss the possible underlying mechanisms.


Subject(s)
Humans , Alzheimer Disease/pathology , Apolipoprotein E4/genetics , Apolipoproteins E/genetics , Genotype , Lipid Metabolism , Neurodegenerative Diseases , Risk Factors
14.
Article in English | WPRIM | ID: wpr-939828

ABSTRACT

Superchilling is an emerging technology for meat preservation; however, the temperature changes during the process have been commonly ignored. Thus, the effects of temperature fluctuations on meat quality during superchilling are yet to be evaluated. In our study, pork loins and salmon fillets were stored for several days (0, 8, 15, 23, and 30 d) under different temperature fluctuations based on -3.5 ℃ as the target temperature. The results showed that after 15 d of superchilling storage, the values of total volatile basic nitrogen, total viable count, and lipid oxidation were significantly (P<0.05) altered in the ±2.0 ℃ fluctuation group compared with the constant temperature group. On the contrary, there was no significant difference in these parameters between the ±1.0 ℃ fluctuation group and the constant temperature group after 30 d of storage. In addition, irregular temperature changes significantly accelerated the modulation of various indicators. In brief, temperature fluctuations and irregular temperature changes accelerated the destruction of muscle structural integrity, increased the water loss, gradually widened the water loss channels, and thereby reduced the edibility by accelerating the spoilage of meat.


Subject(s)
Animals , Lipid Metabolism , Pork Meat , Red Meat , Salmon , Swine , Temperature
15.
Article in English | WPRIM | ID: wpr-939812

ABSTRACT

Renal fibrosis is a common and irreversible pathological feature of end-stage renal disease caused by multiple etiologies. The role of inflammation in renal fibrosis tissue has been generally accepted. The latest view is that fatty acid metabolism disorder contributes to renal fibrosis. peroxisome proliferator activated receptor-gamma coactivator 1α (PGC1α) plays a key role in fatty acid metabolism, regulating fatty acid uptake and oxidized protein synthesis, preventing the accumulation of lipid in the cytoplasm, and maintaining a dynamic balanced state of intracellular lipid. In multiple animal models of renal fibrosis caused by acute or chronic kidney disease, or even age-related kidney disease, almost all of the kidney specimens show the down-regulation of PGC1α. Upregulation of PGC1α can reduce the degree of renal fibrosis in animal models, and PGC1α knockout animals exhibit severe renal fibrosis. Studies have demonstrated that AMP-activated protein kinase (AMPK), MAPK, Notch, tumor necrosis factor-like weak inducer of apoptosis (TWEAK), epidermal growth factor receptor (EGFR), non-coding RNA (ncRNAs), liver kinase B1 (LKB1), hairy and enhancer of split 1 (Hes1), and other pathways regulate the expression of PGC1α and affect fatty acid metabolism. But some of these pathways interact with each other, and the effect of the integrated pathway on renal fibrosis is not clear.


Subject(s)
Animals , Fatty Acids , Fibrosis , Lipid Metabolism , Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/metabolism , Renal Insufficiency, Chronic
16.
Acta Physiologica Sinica ; (6): 443-460, 2022.
Article in Chinese | WPRIM | ID: wpr-939579

ABSTRACT

The mammalian internal circadian clock system has been evolved to adapt to the diurnal changes in the internal and external environment of the organism to regulate diverse physiological functions, such as the sleep-wake cycle and feeding rhythm, thereby coordinating the rhythmic changes of energy demand and nutrition supply in each diurnal cycle. The circadian clock regulates glucose metabolism, lipid metabolism, and hormones secretion in diverse tissues and organs, including the liver, skeletal muscle, pancreas, heart, and vessels. As a special "organ" of the host, the gut microbiota, together with the intestinal microenvironment (tissues, cells, and metabolites) in a co-evolutionary process, constitutes a micro-ecosystem and plays an important role in the process of nutrient digestion and absorption in the intestine of the host. In recent years, accumulating evidence indicates that the compositions, quantities, colonization, and functional activities of the gut microbiota exhibit significant circadian variations, which are closely related to the changes of various physiological functions under the regulation of host circadian clock system. In addition, several studies have shown that the gut microbiota can produce many important metabolites such as the short-chain fatty acids through the degradation of indigestive dietary fibers. A portion of gut microbiota-derived metabolites can regulate the circadian clock system and metabolism of the host. This article mainly discusses the interaction between the host circadian clock system and the gut microbiota, and highlights its influence on energy metabolism of the host, providing a novel clues and thought for the prevention and treatment of metabolic diseases.


Subject(s)
Animals , Circadian Clocks/physiology , Circadian Rhythm/physiology , Ecosystem , Energy Metabolism , Gastrointestinal Microbiome/physiology , Lipid Metabolism/physiology , Mammals
17.
Article in Chinese | WPRIM | ID: wpr-936366

ABSTRACT

OBJECTIVE@#To investigate the changes of tetraspanin 8 (TSPAN8) expression levels and its role in lipid metabolism during the development of non-alcoholic fatty liver disease (NAFLD).@*METHODS@#Thirty male C57BL/6J mice were randomly divided into normal diet group and high-fat diet (HFD) group (n=15), and after feeding for 1, 3, and 6 months, the expression levels of TSPAN8 in the liver tissues of the mice were detected with Western blotting. In a HepG2 cell model of NAFLD induced by free fatty acids (FFA), the effect of TSPAN8 overexpression on lipid accumulation was examined using Oil Red O staining and an automated biochemical analyzer, and the mRNA expressions of the key genes involved in lipid metabolism were detected using qRT-PCR.@*RESULTS@#Western blotting showed that compared with that in mice with normal feeding, the expression of TSPAN8 was significantly decreased in the liver tissues of mice with HFD feeding for 3 and 6 months (P < 0.05). In HepG2 cells, treatment with FFA significantly decreased the expression of TSPAN8 at both the mRNA and protein levels (P < 0.01). TSPAN8 overexpression in FFA-treated cells showed significantly lowered intracellular triglyceride levels (P < 0.001) and obviously reduced mRNA expression of fatty acid transport protein 5 (FATP5) (P < 0.01). The expression of FATP5 was significantly increased in FFA-treated cells as compared with the control cells (P < 0.001).@*CONCLUSION@#TSPAN8 is involved in lipid metabolism in NAFLD, and overexpression of TSPAN8 may inhibit cellular lipid deposition by reducing the expression of FATP5.


Subject(s)
Animals , Male , Mice , Diet, High-Fat/adverse effects , Fatty Acids, Nonesterified , Lipid Metabolism , Liver/metabolism , Mice, Inbred C57BL , Non-alcoholic Fatty Liver Disease/metabolism , RNA, Messenger/metabolism
18.
Article in Chinese | WPRIM | ID: wpr-935736

ABSTRACT

Objective: To investigate the effect of pesticides and herbicides on lipid metabolism. Methods: In November 2020, Based on the data of the national health and Nutrition Survey (NHANES) (2011-2014) , select the population aged 20~65 who have demographic information, pesticide use and data of four lipid metabolism indicators [total cholesterol (TC) , triglyceride (TG) , high density lipoprotein cholesterol (HDLC) and low density lipoprotein cholesterol (LDLC) ] (n=3039) . The subjects were divided into insecticide group (320 people) and non insecticide group (2719) according to the use of insecticides, and herbicide group (156 people) and non herbicide group according to the use of herbicides. Results: Among the 3039 subjects, the males and female were 1509 (49.7%) and 1530 (50.3%) respectively. The males age was (39.7±12.0) years and the females age was (40.2±12.0) years The concentration of HDLC in the NHANES (55.4±15.0) mg/dl was lower than that of (58.2±14.2) mg/dL in the non herbicide group (P<0.05) (b=-0.044, P<0.05) . The results showed that the use of herbicides was related to the decrease of HDLC and the increase of LDLC and LDLC/HDLC in female population (b=-0.050, 0.062, 0.067, all P<0.05) . Conclusion: Herbicide exposure can cause the change of lipid metabolism, and the effect on female population is more obvious.


Subject(s)
Adult , Female , Humans , Male , Middle Aged , Young Adult , Cholesterol, HDL , Cholesterol, LDL , Lipid Metabolism , Nutrition Surveys , Pesticides
19.
Article in Chinese | WPRIM | ID: wpr-928057

ABSTRACT

This paper aims to study the effect of Xiangqin Jiere Granules(XQ) on lipid metabolism and chronic inflammation in different obesity model mice. The monosodium glutamate(MSG) obese mouse model was established by subcutaneous injection of MSG in newborn mice, and the high fat diet(HFD) obese mouse model was established by feeding adult mice with HFD. The normal mice were assigned into the control group; the MSG obese mice were assigned into MSG model group, XQ4.5 group(Xiangqin Jiere Granu-les, 4.5 g·kg~(-1)), XQ22.5 group(Xiangqin Jiere Granules, 22.5 g·kg~(-1)); the HFD obese mice were assigned into HFD model group, XQ4.5 group, and XQ22.5 group. The mice were intragastrically administrated with saline or XQ for 5 weeks. After that, the body weight, visceral fat mass, liver and thymus weight, and the organ indexes in each group were measured. The levels of triglyceride(TG), total cholesterol(TC), and low-density lipoprotein cholesterol(LDL-c) in serum and liver tissue were detected by the kits. The mRNA expression levels of acetyl CoA carboxylase 1(ACC1), fatty acid synthetase(FAS), diacylgycerol acyltransferase 1(DGAT1) and hepatic lipase(HTGL) involved in lipid metabolism in mouse liver tissue were detected by quantitative real-time PCR(qPCR). The protein levels of tumor necrosis factor-α(TNF-α) and interleukin-6(IL-6) in serum were detected by ELISA, and the mRNA levels of TNF-α and IL-6 in liver tissue were detected by qPCR. Compared with the control group, MSG and HFD mice showed increased body weight, abdominal circumference, Lee index and visceral fat mass as well as elevated levels of TG, TC, and LDL-c in serum. The model mice had up-regulated gene levels of ACC1, FAS and DGAT1 while down-regulated gene level of HTGL in the liver. Furthermore, the mRNA and protein levels of IL-6 increased in the model mice. Compared with the model mice, XQ treatment decreased the body weight, abdominal circumference, Lee index, and visceral fat mass, lowered the levels of TG, TC, and LDL-c in se-rum, down-regulated the gene levels of ACC1, FAS, and DGAT1 in liver tissue, up-regulated the gene level of HTGL, and down-regulated the mRNA and protein levels of IL-6. To sum up, XQ has good therapeutic effect on different obesity model mice. It can improve lipid metabolism and reduce fat accumulation in obese mice by regulating the enzymes involved in lipid metabolism, and alleviate obesity-related chronic low-grade inflammation.


Subject(s)
Animals , Mice , Inflammation/metabolism , Lipid Metabolism , Mice, Inbred C57BL , Mice, Obese , Obesity/genetics
20.
Article in English | WPRIM | ID: wpr-927639

ABSTRACT

OBJECTIVE@#This study aimed to investigate the effects of caprylic acid (C8:0) on lipid metabolism and inflammation, and examine the mechanisms underlying these effects in mice and cells.@*METHODS@#Fifty-six 6-week-old male C57BL/6J mice were randomly allocated to four groups fed a high-fat diet (HFD) without or with 2% C8:0, palmitic acid (C16:0) or eicosapentaenoic acid (EPA). RAW246.7 cells were randomly divided into five groups: normal, lipopolysaccharide (LPS), LPS+C8:0, LPS+EPA and LPS+cAMP. The serum lipid profiles, inflammatory biomolecules, and ABCA1 and JAK2/STAT3 mRNA and protein expression were measured.@*RESULTS@#C8:0 decreased TC and LDL-C, and increased the HDL-C/LDL-C ratio after injection of LPS. Without LPS, it decreased TC in mice ( P < 0.05). Moreover, C8:0 decreased the inflammatory response after LPS treatment in both mice and cells ( P < 0.05). Mechanistic investigations in C57BL/6J mouse aortas after injection of LPS indicated that C8:0 resulted in higher ABCA1 and JAK2/STAT3 expression than that with HFD, C16:0 and EPA, and resulted in lower TNF-α, NF-κB mRNA expression than that with HFD ( P < 0.05). In RAW 264.7 cells, C8:0 resulted in lower expression of pNF-κBP65 than that in the LPS group, and higher protein expression of ABCA1, p-JAK2 and p-STAT3 than that in the LPS and LPS+cAMP groups ( P < 0.05).@*CONCLUSION@#Our studies demonstrated that C8:0 may play an important role in lipid metabolism and the inflammatory response, and the mechanism may be associated with ABCA1 and the p-JAK2/p-STAT3 signaling pathway.


Subject(s)
Animals , Humans , Male , Mice , ATP Binding Cassette Transporter 1/immunology , Caprylates/chemistry , Cholesterol/metabolism , Diet, High-Fat/adverse effects , Inflammation/metabolism , Janus Kinase 2/immunology , Lipid Metabolism/drug effects , Macrophages/immunology , Mice, Inbred C57BL , STAT3 Transcription Factor/immunology , Signal Transduction
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