Your browser doesn't support javascript.
Show: 20 | 50 | 100
Results 1 - 20 de 107
Braz. j. biol ; 83: 1-9, 2023. graf, tab
Article in English | LILACS, VETINDEX | ID: biblio-1468949


The present study was designed to investigate the effects of Gundelia tournefortii L. plant extract on different tissues in terms of DNA damage, biochemical and antioxidant parameter values in rats with high-calorie diets. With this aim, Wistar albino male rats were divided into 4 groups containing 6 rats each and the study was completed over 12 weeks duration. At the end of the implementation process over the 12 weeks, rats were sacrificed and blood and tissue samples were obtained. Analyses were performed on blood and tissue samples. According to results for DNA damage (8-OHdG), in brain tissue the OG2 group was significantly reduced compared to the NC group. For MDA results in liver tissue, OG1 and OG2 groups were determined to increase by a significant degree compared to the control group, while the OG2 group was also increased significantly compared to the obese group. In terms of the other parameters, comparison between the groups linked to consumption of a high calorie diet (HCD) and administration of Gundelia tournefortii L. in terms of antioxidant activities and serum samples obtained statistically significant results. Gundelia tournefortii L. plant extracts had effects that may be counted as positive on antioxidant parameter activity and were especially identified to improve DNA damage and MDA levels in brain tissues. Additionally, consumption of Gundelia tournefortii L. plant extract in the diet may have antiobesity effects; thus, it should be evaluated for use as an effective weight-loss method and as a new therapeutic agent targeting obesity.

O presente estudo foi desenhado para investigar os efeitos do extrato da planta Gundelia tournefortii L. em diferentes tecidos em termos de danos ao DNA, valores de parâmetros bioquímicos e antioxidantes em ratos com dietas hipercalóricas. Com esse objetivo, ratos Wistar albinos machos foram divididos em 4 grupos contendo 6 ratos cada e o estudo foi concluído ao longo de 12 semanas de duração. No final desse processo de implementação, os ratos foram sacrificados e amostras de sangue e tecido foram obtidas. As análises foram realizadas em amostras de sangue e tecido. De acordo com os resultados para danos ao DNA (8-OHdG), no tecido cerebral o grupo OG2 foi significativamente reduzido em comparação com o grupo NC. Para os resultados de MDA no tecido hepático, os grupos OG1 e OG2 aumentaram significativamente em comparação ao grupo controle, enquanto o grupo OG2 também aumentou significativamente em comparação ao grupo obeso. Quanto aos demais parâmetros, a comparação entre os grupos ligados ao consumo de dieta hipercalórica (DC) e à administração de Gundelia tournefortii L. em termos de atividades antioxidantes e amostras de soro obteve resultados estatisticamente significativos. Os extratos de plantas de Gundelia tournefortii L. tiveram efeitos que podem ser considerados positivos na atividade dos parâmetros antioxidantes e foram especialmente identificados para melhorar os danos ao DNA e os níveis de MDA nos tecidos cerebrais. Além disso, o consumo de extrato vegetal de Gundelia tournefortii L. na dieta pode ter efeitos antiobesidade; portanto, deve ser avaliado para uso como um método eficaz de perda de peso e como um novo agente terapêutico voltado para a obesidade.

Male , Animals , Rats , Antioxidants/analysis , Asteraceae/chemistry , Diet/adverse effects , Rats, Wistar/anatomy & histology , Rats, Wistar/genetics , Rats, Wistar/blood , Mice, Obese
Braz. j. biol ; 83: 1-8, 2023. tab, ilus, graf
Article in English | LILACS, VETINDEX | ID: biblio-1469007


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.

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.

Animals , Rats , Diet, High-Fat , Fatty Liver/drug therapy , Fatty Liver/veterinary , Obesity/drug therapy , Portulaca , Mice, Obese
Chinese journal of integrative medicine ; (12): 617-625, 2023.
Article in English | WPRIM | ID: wpr-982270


OBJECTIVE@#To investigate whether astragalus polysaccharides (APS) combined with berberine (BBR) can reduce high-fat diet (HFD)-induced obesity in mice.@*METHODS@#Except for normal mice, 32 HFD-induced obese mice were randomized into HFD, APS (1,000 mg/kg APS), BBR (200 mg/kg BBR), and APS plus BBR (1,000 mg/kg APS plus 200 mg/kg BBR) groups, respectively. After 6-week treatment (once daily by gavage), the obesity phenotype and pharmacodynamic effects were evaluated by histopathological examination of epididymal fat, liver, and colon using hematoxylin-eosin staining and serum biochemical analyses by an automated chemistry analyzer. The feces were collected at the 12 th week, and taxonomic and functional profiles of gut microbiota were analyzed by 16S ribosomal ribonucleic acid (16S rRNA) sequencing.@*RESULTS@#Compared with HFD group, the average body weight of APS plus BBR group was decreased (P<0.01), accompanied with the reduced fat accumulation, enhanced colonic integrity, insulin sensitivity and glucose homeostasis (P<0.05 or P<0.01). Importantly, APS combined with BBR treatment was more effective than APS or BBR alone in improving HFD-induced insulin resistance (P<0.05 or P<0.01). 16S rRNA sequence-based analysis of fecal samples demonstrated that APS combined with BBR treatment exhibited a better impact on HFD-induced gut microbiota dysbiosis, exclusively via the enriched abundances of Bacteroides, which corresponded to the large increase of predicted bacterial genes involved in carbohydrate metabolism.@*CONCLUSION@#APS combined with BBR may synergistically reduce obesity and modulate the gut microbiota in HFD-fed mice.

Mice , Animals , Diet, High-Fat , Berberine/therapeutic use , Mice, Obese , RNA, Ribosomal, 16S/genetics , Gastrointestinal Microbiome , Obesity/drug therapy , Insulin Resistance , Mice, Inbred C57BL
China Journal of Chinese Materia Medica ; (24): 1751-1759, 2023.
Article in Chinese | WPRIM | ID: wpr-981392


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.

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
Biol. Res ; 56: 14-14, 2023. ilus, graf
Article in English | LILACS | ID: biblio-1429914


The endocannabinoid system (ECS) regulates energy metabolism, has been implicated in the pathogenesis of metabolic diseases and exerts its actions mainly through the type 1 cannabinoid receptor (CB1). Likewise, autophagy is involved in several cellular processes. It is required for the normal development of muscle mass and metabolism, and its deregulation is associated with diseases. It is known that the CB1 regulates signaling pathways that control autophagy, however, it is currently unknown whether the ECS could regulate autophagy in the skeletal muscle of obese mice. This study aimed to investigate the role of the CB1 in regulating autophagy in skeletal muscle. We found concomitant deregulation in the ECS and autophagy markers in high-fat diet-induced obesity. In obese CB1-KO mice, the autophagy-associated protein LC3 II does not accumulate when mTOR and AMPK phosphorylation levels do not change. Acute inhibition of the CB1 with JD-5037 decreased LC3 II protein accumulation and autophagic flux. Our results suggest that the CB1 regulates autophagy in the tibialis anterior skeletal muscle in both lean and obese mice.

Animals , Mice , Cannabinoids/metabolism , Autophagy/physiology , Muscle, Skeletal/metabolism , Receptor, Cannabinoid, CB1/metabolism , Mice, Inbred C57BL , Mice, Obese
São Paulo; s.n; s.n; 2022. 54 p. graf.
Thesis in English | LILACS | ID: biblio-1396676


Skeletal muscle is an important metabolic tissue in glucose uptake and thus in glycemic homeostasis. Evidence suggests that phenolic compounds may exert beneficial health effects against metabolic disorders associated to obesity including its state of peripheral insulin resistance. The objective of this work was to investigate the role of phenolic compounds present in two Brazilian native fruits, cambuci (Campomanesia phaea Berg.) and jaboticaba (Plinia jaboticaba (Vell.) Berg), on the insulin resistance in the skeletal muscle of obese mice fed a high-fat-sucrose diet (HFS). For this, two independent experimental protocols were used for each fruit, where male C57BL/6J mice fed the HFS diet for the induction to obesity were used. Once the condition of obesity was established, animals started to receive daily oral administration (by gavage) of extracts enriched in phenolic compounds obtained from each fruit, in doses reachable through the diet. At the end of the experiments, the animals were euthanized and their tissue and organs collected. The animals receiving extracts of jaboticaba and cambuci, regardless of the dose, presented lower body weight gain in relation to the HFS group. The results for weekly fasting glycemia and glucose tolerance of the animals that received the phenolic extracts of both fruits showed an improvement in glycemic homeostasis even when fed with the deleterious diet. In the gastrocnemius muscle of the animals was demonstrated that cambuci and jaboticaba extracts significantly increased the content of glucose transporter protein 4 (GLUT-4) and AMPactivated protein kinase (AMPK-Thr172), which has a broad role in metabolic regulation. Regarding inflammation, the administration of extracts from both fruits favored the reduction of phosphorylation and activation of the nuclear factor-κe (NF-κB) and the expression of some genes such as IL-6, TNF-α, IL-1ß, and JNK, whose increase has been associated with insulin resistance. In conclusion, this study suggests that the phenolics present in both native fruits may be important therapeutic agents in the reduction of muscle insulin resistance and inflammation associated with obesity

O músculo esquelético é um tecido metabólico importante na captação de glicose e, portanto, na homeostasia glicêmica. Evidências sugerem que compostos fenólicos podem exercer efeitos benéficos à saúde contra distúrbios metabólicos associados à obesidade incluindo o seu quadro de resistência à insulina. O objetivo deste trabalho foi investigar o papel dos compostos fenólicos presentes em dois frutos nativos brasileiros, cambuci (Campomanesia phaea Berg.) e jaboticaba (Plinia jaboticaba (Vell.) Berg), na resistência à insulina no músculo esquelético de camundongos obesos alimentados com dieta rica em gorduras e sacarose (HFS, high-fat highsucrose diet). Para tal, foram utilizados dois protocolos experimentais independentes para cada fruto, onde foram usados camundongos machos C57BL/6J alimentados com dieta HFS para indução à obesidade. Uma vez instaurado o quadro de obesidade, os animais passaram a receber a administração diária, por gavagem, de extratos enriquecidos em compostos fenólicos obtidos a partir dos frutos, em doses atingíveis através da dieta. Ao final do período experimental os animais foram eutanasiados e seus tecidos e órgãos coletados. Os animais tratados com os extratos de jaboticaba e cambuci, independente da dose, apresentaram menor ganho de massa corporal em relação ao grupo HFS. Os resultados para glicemia de jejum semanal e a tolerância à glicose dos animais que receberam os extratos fenólicos de ambos os frutos demonstraram melhora na homeostase glicêmica, mesmo alimentados com a dieta deletéria HFS. No músculo gastrocnemius dos animais foi demonstrado que os extratos de cambuci e jaboticaba aumentaram significativamente o conteúdo da proteína transportadora de glicose 4 (GLUT-4) e da proteína quinase ativada por AMP (AMPK-Thr172), que possui um papel amplo na regulação metabólica. No que tange à inflamação, a administração dos extratos de ambos os frutos favoreceu a diminuição da fosforilação e ativação do fator nuclear-κB (NF-κB) e a expressão de alguns genes como IL-6, TNF-α, IL-1ß, e JNK cujo aumento tem sido associado com a resistência à insulina. Deste modo, este estudo sugere que os fenólicos presentes em ambos os frutos nativos podem ser agentes terapêuticos importantes na atenuação da resistência à insulina muscular e da inflamação associada à obesidade

Animals , Male , Mice , Muscle, Skeletal , Phenolic Compounds , Fruit/anatomy & histology , Insulin/pharmacology , Myrtaceae/classification , Mice, Obese , Obesity/chemically induced
Journal of Southern Medical University ; (12): 1032-1037, 2022.
Article in Chinese | WPRIM | ID: wpr-941037


OBJECTIVE@#To observe the effect of mibefradil on skeletal muscle mass, function and structure in obese mice.@*METHODS@#Fifteen 6-week-old C57BL/6 mice were randomized equally into normal diet group (control group), high-fat diet (HFD) group and high-fat diet +mibefradil intervention group (HFD +Mibe group). The grip strength of the mice was measured using an electronic grip strength meter, and the muscle content of the hindlimb was analyzed by X-ray absorptiometry (DXA). Triglyceride (TG) and total cholesterol (TC) levels of the mice were measured with GPO-PAP method. The cross-sectional area of the muscle fibers was observed with HE staining. The changes in the level of autophagy in the muscles were detected by Western blotting and immunofluorescence assay, and the activation of the Akt/mTOR signaling pathway was detected with Western blotting.@*RESULTS@#Compared with those in the control group, the mice in HFD group had a significantly greater body weight, lower relative grip strength, smaller average cross sectional area of the muscle fibers, and a lower hindlimb muscle ratio (P < 0.05). Immunofluorescence assay revealed a homogenous distribution of LC3 emitting light red fluorescence in the cytoplasm in the muscle cells in HFD group and HFD+Mibe group, while bright spots of red fluorescence were detected in HFD group. In HFD group, the muscular tissues of the mice showed an increased expression level of LC3 II protein with lowered expressions of p62 protein and phosphorylated AKT and mTOR (P < 0.05). Mibefradil treatment significantly reduced body weight of the mice, lowered the expression level of p62 protein, and increased forelimb grip strength, hindlimb muscle ratio, cross-sectional area of the muscle fibers, and the expression levels of LC3 II protein and phosphorylated AKT and mTOR (P < 0.05).@*CONCLUSION@#Mibefradil treatment can moderate high-fat diet-induced weight gain and improve muscle mass and function in obese mice possibly by activating AKT/mTOR signal pathway to improve lipid metabolism and inhibit obesityinduced autophagy.

Animals , Mice , Body Weight , Diet, High-Fat , Mibefradil/metabolism , Mice, Inbred C57BL , Mice, Obese , Muscle, Skeletal/metabolism , Proto-Oncogene Proteins c-akt/metabolism , TOR Serine-Threonine Kinases/metabolism
China Journal of Chinese Materia Medica ; (24): 1307-1315, 2022.
Article in Chinese | WPRIM | ID: wpr-928057


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.

Animals , Mice , Inflammation/metabolism , Lipid Metabolism , Mice, Inbred C57BL , Mice, Obese , Obesity/genetics
Arq. bras. cardiol ; 117(4): 715-725, Oct. 2021. tab, graf
Article in Portuguese | LILACS | ID: biblio-1345249


Resumo Fundamentos A L-carnitina (LC) tem muitos efeitos benéficos em animais diabéticos e humanos, mas seu efeito regulatório sobre a quemerina como uma citocina inflamatória e seu receptor no estado diabético são desconhecidos. Objetivos O presente estudo teve como objetivo investigar o efeito regulatório da LC na expressão do receptor semelhante ao de quimiocina 1 e quemerina (CMKLRI) em tecidos adiposo e cardíaco de camundongos diabéticos. Métodos Sessenta camundongos NMARI foram divididos em quatro grupos, incluindo controle, diabético, diabético + suplementação com LC e controle + suplementação com LC. O diabetes foi induzido pela alimentação dos animais com dieta hipercalórica por 5 semanas e injeção de estreptozotocina. Os animais foram tratados com 300 mg/kg de LC por 28 dias. Nos dias 7, 14 e 28 após o tratamento, os níveis de mRNA e proteína da quemerina e CMKLRI nos tecidos cardíacos e adiposos de animais foram determinados utilizando análise por qPCR e ELISA. Os índices de resistência à insulina também foram medidos em todos os grupos experimentais. A diferença com p<0,05 foi considerada significativa. Resultados A expressão de quemerina e CMKLRI aumentou nos tecidos cardíaco e adiposo de camundongos diabéticos nos dias 14 e 28 após a indução do diabetes, concomitantemente com a incidência de resistência à insulina e níveis aumentados de quemerina circulante (p<0,05). O tratamento com LC causou uma diminuição significativa na expressão de ambos os genes nos tecidos estudados e redução dos sintomas de resistência à insulina e dos níveis séricos de quemerina (p<0,05). Conclusão Os resultados sugerem que o tratamento com LC pode diminuir a expressão de quemerina e CKLR1 em tecidos cardíacos e adiposos de animais experimentais obesos e diabéticos.

Abstract Background L-carnitine (LC) has many beneficial effects on diabetic animals and humans, but its regulatory effect on chemerin as an inflammatory cytokine, and its receptor in diabetes status is unknown. Objectives The present study aimed to investigate the regulatory effect of LC on the expression of chemerin and chemokine-like receptor I (CMKLRI) in adipose and cardiac tissues of diabetic mice. Methods Sixty NMARI mice were divided into four groups including control, diabetic, diabetic + LC supplementation and control + LC supplementation. Diabetes was induced by feeding the animals a high-calorie diet for 5 weeks and injection of Streptozotocin. The animals were treated with 300 mg/kg LC for 28 days. On days 7, 14, and 28 after treatment, the mRNA and protein levels of chemerin and CMKLRI in the cardiac and adipose tissues of the animals were determined using qPCR analysis and ELISA. Insulin resistance indices were also measured in all experimental groups. Differences with p <0.05 were considered significant. Results Chemerin and CMKLRI expressions levels were increased in cardiac and adipose tissues of diabetic mice on days 14 and 28 after diabetes induction, concurrent with the incidence of insulin resistance and increased levels of circulating chemerin (p<0.05). The treatment with LC caused a significant decrease in the expression of both genes in studied tissues and the reduction of insulin resistance symptoms and serum chemerin levels (p<0.05). Conclusion The results suggest that LC treatment were able to downregulate the expression of chemerin and CKLR1 in cardiac and adipose tissues of obese, diabetic experimental animals.

Animals , Mice , Receptors, Chemokine , Diabetes Mellitus, Experimental/drug therapy , Carnitine/pharmacology , Chemokines , Intercellular Signaling Peptides and Proteins , Mice, Obese , Obesity/drug therapy
São Paulo; s.n; s.n; 2021. 79 p. graf, tab.
Thesis in English | LILACS | ID: biblio-1396698


Jaboticaba (Plinia jaboticaba (Vell.) Berg) is a Brazilian native fruit belonging to the Myrtaceae family. Previously it was demonstrated that phenolicrich extracts from jaboticaba (PEJ) possess health-beneficial properties in dietinduced obesity; however, whether PEJ modulates the obesity-associated intestinal inflammatory status remains unclear. The objective of the present study was to evaluate the effect of PEJ on intestinal inflammation associated with obesity induced by a high-fat-sucrose (HFS) diet. Thus, forty male C57BL/6J mice were distributed into two groups: negative control (CH, 10 animals), fed standard diet AIN96M and water ad libitum; and positive control (HFS, 30 animals), fed HFS diet and water ad libitum induced to obesity for an initial period of 14 weeks. After this period, the HFS group was redistributed in three groups of 10 animals each, and continuously fed HFS diet for another 14 weeks: HFS group received daily gavages of water, PEJ1 group received PEJ at the dose of 50 mg of gallic acid equivalent (GAE)/kg body weight (BW and PEJ2 group received PEJ at the dose of 100 mg GAE/kg BW. Feed intake and body mass were monitored weekly, and fasting glucose biweekly. The initial period of obesity-induction demonstrated that the HFS diet was efficient to promote a significant body weight gain and fasting hyperglycemia when compared to the negative control group (CH). At the end of the experiment the animals were euthanized under anesthesia and their organs and tissues were collected. The major classes of phenolic compounds found in PEJ were ellagitannins, anthocyanins including cyanidin and delphinidin glycosides, proanthocyanidins, and free ellagic acid. PEJ-treated animals presented a reduced body weight gain, adiposity and demonstrated significant reversion of insulin resistance and dyslipidemia. In addition, the inflammatory profile of colon demonstrated that PEJ prevented metabolic endotoxemia linked to an attenuation of the HFS diet-induced intestinal inflammation via downregulation of pro-inflammatory mediators such as tumor necrosis factor (TNF-ß), membrane transporter toll-like receptor-4 (TLR-4) and nuclear factor-κB (NF-κB) in the colon. These anti-inflammatory effects appear to be involved, at least in part, with an inhibition of the colonic inflammasome pathway of obese mice. Collectively, our data reveals that PEJ exerts a direct anti-inflammatory effect in obesity-associated intestinal inflammation and this outcome is linked to an amelioration of metabolic endotoxemia in obese mice

A jabuticaba (Plinia jaboticaba (Vell.) Berg) é uma fruta nativa brasileira pertencente à família Myrtaceae. Anteriormente, foi demonstrado que extratos ricos em fenólicos de jabuticaba (PEJ) possuem propriedades benéficas à saúde na obesidade induzida por dieta; no entanto, se o PEJ modula o estado inflamatório intestinal associado à obesidade ainda não está claro. O objetivo do presente estudo foi avaliar o efeito do PEJ na inflamação intestinal associada à obesidade induzida por uma dieta rica em sacarose (HFS). Assim, quarenta camundongos C57BL / 6J machos foram distribuídos em dois grupos: controle negativo (CH, 10 animais), alimentados com dieta padrão AIN96M e água ad libitum; e controle positivo (HFS, 30 animais), alimentado com dieta HFS e água ad libitum induzida à obesidade por um período inicial de 14 semanas. Após este período, o grupo HFS foi redistribuído em três grupos de 10 animais cada, e continuamente alimentado com dieta HFS por mais 14 semanas: o grupo HFS recebeu gavagens diárias de água, o grupo PEJ1 recebeu PEJ na dose de 50 mg de ácido gálico equivalente (GAE) / kg de peso corporal (pc) e o grupo PEJ2 recebeu PEJ na dose de 100 mg GAE / kg pc. O consumo de ração e a massa corporal foram monitorados semanalmente e a glicemia de jejum quinzenal. O período inicial de indução da obesidade demonstrou que a dieta HFS foi eficiente em promover significativo ganho de peso corporal e hiperglicemia de jejum quando comparada ao grupo controle negativo (HC). Ao final do experimento os animais foram submetidos à eutanásia sob anestesia e seus órgãos e tecidos coletados. As principais classes de compostos fenólicos encontrados em PEJ foram elagitaninos, antocianinas incluindo cianidina e delfinidina glicosiladas, proantocianidinas e ácido elágico livre. Os animais tratados com PEJ apresentaram redução do ganho de peso corporal, adiposidade e reversão significativa da resistência à insulina e dislipidemia. Além disso, o perfil inflamatório do cólon demonstrou que o PEJ evitou a endotoxemia metabólica ligada a uma atenuação da inflamação intestinal induzida pela dieta de HFS por meio da regulação negativa de mediadores pró-inflamatórios, como o fator de necrose tumoral (TNF-), transportador de membrana toll- como o receptor 4 (TLR-4) e o fator nuclear B (NF-B) no cólon. Esses efeitos anti-inflamatórios parecem estar envolvidos, pelo menos em parte, com uma inibição da via do inflamassoma colônico de camundongos obesos. Coletivamente, nossos dados revelam que o PEJ exerce um efeito anti-inflamatório direto na inflamação intestinal associada à obesidade e esse resultado está relacionado com uma melhora da endotoxemia metabólica em camundongos obesos

Animals , Male , Mice , Myrtaceae/classification , Phenolic Compounds , Fruit/metabolism , Insulin Resistance , Weight Gain , Tumor Necrosis Factor-alpha/adverse effects , Diet , Eating , Mice, Obese/classification , Anti-Inflammatory Agents/adverse effects , Obesity/drug therapy
Journal of Integrative Medicine ; (12): 439-450, 2021.
Article in English | WPRIM | ID: wpr-888766


OBJECTIVE@#To evaluate the synergic effects of a novel oral supplement formulation, containing prebiotics, yeast β-glucans, minerals and silymarin (Silybum marianum), on lipid and glycidic metabolism, inflammatory and mitochondrial proteins of the liver, in control and high-fat diet-induced obese mice.@*METHODS@#After an acclimation period, 32 male C57BL/6 mice were divided into the following groups: nonfat diet (NFD) vehicle, NFD supplemented, high-fat diet (HFD) vehicle and HFD supplemented. The vehicle and experimental formulation were administered orally by gavage once a day during the last four weeks of the diet (28 consecutive days). We then evaluated energy homeostasis, inflammation, and mitochondrial protein expression in these groups of mice.@*RESULTS@#After four weeks of supplementation, study groups experienced reduced glycemia, dyslipidemia, fat, and hepatic fibrosis levels. Additionally, proliferator-activated receptor-α, AMP-activated protein kinase-1α, peroxisome proliferator-activated receptor γ co-activator-1α, and mitochondrial transcription factor A expression levels were augmented; however, levels of inhibitor of nuclear factor-κB kinase subunit α and p65 nuclear factor-κB expression, and oxidative markers were reduced. Notably, the cortisol/C-reactive protein ratio, a well-characterized marker of the hypothalamic-pituitary-adrenal axis immune interface status, was found to be modulated by the supplement.@*CONCLUSION@#We discovered that the novel supplement was able to modify different antioxidant, metabolic and inflammatory pathways, improving the energy homeostasis and inflammatory status, and consequently alleviated hepatic steatosis.

Animals , Mice , Antioxidants , Dietary Supplements , Glucans , Hypothalamo-Hypophyseal System , Liver , Mice, Inbred C57BL , Mice, Obese , Silybum marianum , Minerals , Pituitary-Adrenal System , Prebiotics , Saccharomyces cerevisiae
China Journal of Chinese Materia Medica ; (24): 2104-2111, 2021.
Article in Chinese | WPRIM | ID: wpr-879136


The aim of this study was to elucidate the mechanism of nuciferine on alleviating obesity based on modulating gut microbiota, ameliorating chronic inflammation, and improving gut permeability. In this study, the obese model mice were induced by high-fat diet and then randomly divided into model group, and nuciferine group; some other mice of the same week age were fed with normal diet as normal group. In the modeling process, the mice were administered intragastrically(ig) for 12 weeks. In the course of both modeling and treatment, the body weight and food intake of mice in each group were measured weekly. After modeling and treatment, the Lee's index, weight percentage of inguinal subcutaneous fat, and the level of blood lipid in each group were measured. The pathological changes of adipocytes were observed by HE staining to evaluate the efficacy of nuciferine treatment in obese model mice. 16 S rRNA sequencing analysis was conducted to study the changes in diversity and abundance of gut microbiota after nuciferine treatment. Enzyme-linked immunosorbent assay(ELISA) and quantitative Real-time polymerase chain reaction(qPCR) were used to detect the levels of inflammatory factors interleukin-6(IL-6), interleukin-1β(IL-1β), tumor necrosis factor-α(TNF-α) and the expression of related genes in adipose tissue of mice in each group, so as to evaluate the effect of nuciferine on chronic inflammation of mice in obese model group. qPCR was used to detect the expression of occludin and tight junction protein 1(ZO-1)gene in colon tissure, so as to evaluate the effect of nuciferine on intestinal permeability of mice in obese group. Nuciferine decreased the body weight of obese mice, Lee's index, weight percentage of inguinal subcutaneous fat(P<0.05), and reduced the volume of adipocytes, decreased the level of total cholesterol(TC), triglyceride(TG), and low density lipoprotein cholesterol(LDL-C)(P<0.05) in serum, improved dysbacteriosis, increased the relative abundance of Alloprevotella, Turicibacter, and Lactobacillus, lowered the relative abundance of Helicobac-ter, decreased the expression of inflammatory cytokines IL-6, IL-1β, and TNF-α genes in adipose tissue(P<0.01), decreased the levels of inflammatory cytokines IL-6, IL-1β, and TNF-α in serum(P<0.05), and increased the expression of occludin and ZO-1 genes related to tight junction in colon tissue(P<0.01). Nuciferine could treat obesity through modulating gut microbiota, decreasing gut permeability and ameliorating inflammation.

Animals , Mice , Aporphines , Diet, High-Fat/adverse effects , Gastrointestinal Microbiome , Mice, Inbred C57BL , Mice, Obese , Obesity/genetics
China Journal of Chinese Materia Medica ; (24): 171-176, 2021.
Article in Chinese | WPRIM | ID: wpr-878926


The aim of this paper was to study the effect and mechanism of fucoxanthin on insulin resistance of obese mice induced by high-fat diet. Fifty C57 BL/6 J male mice were randomly divided into control group and high-fat diet group. The insulin resistance model was induced with high-fat diet for 12 weeks, and model mice were randomly divided into model group, fucoxanthin-0.2% group, fucoxanthin-0.4% group and metformin group. After dietary treatment for 6 weeks, the body weight and epididymal fat weight in each group were measured. Fasting blood glucose(FBG), fasting insulin(FINS), total cholesterol(TC), triglyceride(TG), low-density lipoprotein(LDL-C) and high-density lipoprotein(HDL-C) were measured, and insulin resistance index(HOMA-IR) was calcula-ted. The pathological morphology in liver was observed by hematoxylin eosin staining, and the expressions of some key proteins in insulin receptor substrate 1(IRS-1)/posphoinositide 3-kinase(PI3 K)/serine-threonine kinase(Akt) and peroxisome proliferators-activated receptor-γ(PPARγ)/sterol regulatory element binding protein-1(SREBP-1)/fatty acid synthetase(FAS) pathways in liver were detected by Western blot. According to the findings, compared with the model group, levels of body weight, epididymal fat weight, FBG, FINS, TC, TG, LDL-C and HOMA-IR, as well as protein expressions of PPARγ, SREBP-1 and FAS in liver were significantly reduced(P<0.05 or P<0.01), while level of HDL-C and protein expressions of p-IRS-1, IRS-1, PI3 K and p-Akt in liver were signi-ficantly increased after treatment with fucoxanthin(P<0.05 or P<0.01). And the pathological changes of liver tissue in fucoxanthin-treated mice were also improved obviously. The results showed that fucoxanthin could improve obesity, hyperglycemia and hyperlipidemia, and alleviate insulin resistance in obese mice, and its mechanism is possibly related to the regulation of IRS-1/PI3 K/Akt and PPARγ/SREBP-1/FAS pathways.

Animals , Male , Mice , Diet, High-Fat/adverse effects , Insulin , Insulin Resistance , Liver , Mice, Obese , Xanthophylls
Chinese Acupuncture & Moxibustion ; (12): 177-182, 2021.
Article in Chinese | WPRIM | ID: wpr-877566


OBJECTIVE@#To observe the effect of acupoint thread-embedding at "Zusanli" (ST 36) and "Fenglong" (ST 40) on the macrophage polarization of epididymis adipose tissue in obese mice, and to explore the action mechanism of acupoint thread-embedding on weight control.@*METHODS@#Among 30 male C57BL/6 mice, 10 mice were randomly selected and fed with normal diet, and the remaining 20 mice were fed with high-fat diet to establish the obesity model. Sixteen mice with successful obesity model were randomly divided into a model group and an acupoint thread-embedding group, 8 mice in each group. Eight mice were selected from mice which were fed with normal diet as the normal group. On the next day of successful modeling, acupoint thread-embedding was performed at "Zusanli" (ST 36) and "Fenglong" (ST 40) in the acupoint thread-embedding group, once every 10 days for 4 times. The body weight was recorded at 0, 8, 16, 24, 32, 40 days into intervention; the level of glucose metabolism was compared after intervention; the level of lipid metabolism and weight of epididymal adipose tissue were compared at the end of the intervention; the mRNA expression of M1 and M2 macrophage-related cytokines interleukin-10 (IL-6), monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor-α (TNF-α) and interleukin-10 (IL-10) were detected by real-time PCR; the mRNA and protein expression of M1 macrophage labeled inducible nitric oxide synthase (iNOS) and M2 macrophage labeled arginase-1 (Arg-1) were detected by real-time PCR and Western blot.@*RESULTS@#Compared with the normal group, the body weight at 0, 8, 16, 24, 32, 40 days into intervention in the model group was increased (@*CONCLUSION@#Acupoint thread-embedding at "Zusanli" (ST 36) and "Fenglong" (ST 40) may play a role in weight control by regulating the polarization of macrophages.

Animals , Male , Mice , Acupuncture Points , Adipose Tissue , Epididymis , Macrophages , Mice, Inbred C57BL , Mice, Obese
Einstein (Säo Paulo) ; 18: eAO4876, 2020. tab, graf
Article in English | LILACS | ID: biblio-1039734


ABSTRACT Objective To investigate the effects of sericin extracted from silkworm Bombyx mori cocoon on morphophysiological parameters in mice with obesity induced by high-fat diet. Methods Male C57Bl6 mice aged 9 weeks were allocated to one of two groups - Control and Obese, and fed a standard or high-fat diet for 10 weeks, respectively. Mice were then further subdivided into four groups with seven mice each, as follows: Control, Control-Sericin, Obese, and Obese-Sericin. The standard or high fat diet was given for 4 more weeks; sericin (1,000mg/kg body weight) was given orally to mice in the Control-Sericin and Obese-Sericin Groups during this period. Weight gain, food intake, fecal weight, fecal lipid content, gut motility and glucose tolerance were monitored. At the end of experimental period, plasma was collected for biochemical analysis. Samples of white adipose tissue, liver and jejunum were collected and processed for light microscopy analysis; liver fragments were used for lipid content determination. Results Obese mice experienced significantly greater weight gain and fat accumulation and had higher total cholesterol and glucose levels compared to controls. Retroperitoneal and periepididymal adipocyte hypertrophy, development of hepatic steatosis, increased cholesterol and triglyceride levels and morphometric changes in the jejunal wall were observed. Conclusion Physiological changes induced by obesity were not fully reverted by sericin; however, sericin treatment restored jejunal morphometry and increased lipid excretion in feces in obese mice, suggesting potential anti-obesity effects.

RESUMO Objetivo Investigar os efeitos da sericina extraída de casulos de Bombyx mori na morfofisiologia de camundongos com obesidade induzida por dieta hiperlipídica. Métodos Camundongos machos C57Bl6, com 9 semanas de idade, foram distribuídos em Grupos Controle e Obeso, que receberam ração padrão para roedores ou dieta hiperlipídica por 10 semanas, respectivamente. Posteriormente, os animais foram redistribuídos em quatro grupos, com sete animais cada: Controle, Controle-Sericina, Obeso e Obeso-Sericina. Os animais permaneceram recebendo ração padrão ou hiperlipídica por 4 semanas, período no qual a sericina foi administrada oralmente na dose de 1.000mg/kg de massa corporal aos Grupos Controle-Sericina e Obeso-Sericina. Parâmetros fisiológicos, como ganho de peso, consumo alimentar, peso das fezes em análise de lipídios fecais, motilidade intestinal e tolerância à glicose foram monitorados. Ao término do experimento, o plasma foi coletado para dosagens bioquímicas e fragmentos de tecido adiposo branco; fígado e jejuno foram processados para análises histológicas, e amostras hepáticas foram usadas para determinação lipídica. Resultados Camundongos obesos apresentaram ganho de peso e acúmulo de gordura significativamente maior que os controles, aumento do colesterol total e glicemia. Houve hipertrofia dos adipócitos retroperitoneais e periepididimais, instalação de esteatose e aumento do colesterol e triglicerídeos hepáticos, bem como alteração morfométrica da parede jejunal. Conclusão O tratamento com sericina não reverteu todas as alterações fisiológicas promovidas pela obesidade, mas restaurou a morfometria jejunal e aumentou a quantidade de lipídios eliminados nas fezes dos camundongos obesos, apresentando-se como potencial tratamento para a obesidade.

Animals , Male , Anti-Obesity Agents/therapeutic use , Sericins/therapeutic use , Obesity/drug therapy , Time Factors , Triglycerides/analysis , Body Weight/drug effects , Gastrointestinal Transit/drug effects , Weight Gain/drug effects , Adipose Tissue/pathology , Cholesterol/analysis , Reproducibility of Results , Treatment Outcome , Anti-Obesity Agents/pharmacology , Sericins/pharmacology , Eating/drug effects , Fatty Liver/pathology , Diet, High-Fat/adverse effects , Glucose Tolerance Test , Liver/metabolism , Mice, Inbred C57BL , Mice, Obese , Obesity/etiology , Obesity/physiopathology
Einstein (Säo Paulo) ; 18: eAO4784, 2020. tab, graf
Article in English | LILACS | ID: biblio-1039736


ABSTRACT Objective To evaluate the effect of three types of muscular resistance training on adiposity, inflammation levels and insulin activity in Swiss mice with fat-rich diet-induced obesity. Methods Lean and obese male Swiss mice were selected and allocated to one of eight groups comprising eight mice each, as follows: standard diet + no training; standard diet + muscular resistance training; standard diet + hypertrophy training; standard diet + strength training; high-fat diet + no training; high-fat diet + muscular resistance training; high-fat diet + hypertrophy training; high-fat diet + strength training. The training protocol consisted of stair climbing for a 10-week period. Blood samples were collected for lactate analysis, glucose level measurement and insulin tolerance test. After euthanasia, adipose tissues were removed and weighed for adiposity index determination. Fragments of epididymal adipose tissue were then embedded for histological analysis or homogenized for tumor necrosis factor alpha level determination using the ELISA method. Results Ausency of differences in total training volume and blood lactate levels overall emphasize the similarity between the different resistance training protocols. Body weight loss, reduced adipocyte area and lower adiposity index were observed in trained obese mice, regardless of training modality. Different training protocols also improved insulin sensitivity and reduced inflammation levels. Conclusion Resistance training protocols were equally effective in reducing body fat, inflammation levels and insulin resistance in obese mice.

RESUMO Objetivo Avaliar os efeitos de três tipos de treinamentos de resistência na adiposidade, na inflamação e na ação da insulina em camundongos Swiss obesos por dieta hiperlipídica. Métodos Camundongos Swiss machos magros e obesos foram selecionados e posteriormente separados em oito grupos com oito animais em cada: dieta padrão + não treinado; dieta padrão + treinamento de resistência muscular; dieta padrão + treinamento de hipertrofia; dieta padrão + treinamento de força; dieta hiperlipídica + não treinado; dieta hiperlipídica + treinamento de resistência muscular; dieta hiperlipídica + treinamento de hipertrofia; e dieta hiperlipídica + treinamento de força. O protocolo de treinamento consistiu em escaladas, por um período de 10 semanas. Amostras de sangue foram coletadas para análises de lactato, glicemia e teste de tolerância à insulina. Após eutanásia, os tecidos adiposos foram retirados e pesados para determinar o índice de adiposidade. Em seguida, parte do tecido adiposo epididimal foi emblocado para análises histológicas, e outra parte foi homogeneizada para análises de fator de necrose tumoral alfa por ELISA. Resultados O volume total de treinamento e a concentração sanguínea de lactato não diferiram entre os três treinos resistidos, sugerindo similaridade entre eles. Nos animais obesos, as três modalidades de treinamento reduziram o peso corporal, a área adipocitária e o índice de adiposidade. Os três tipos de treinamentos ainda melhoraram a tolerância à insulina e reduziram a inflamação. Conclusão Os protocolos de treinamento resistido foram igualmente efetivos em reduzir a adiposidade, a inflamação e a resistência à ação da insulina em camundongos obesos.

Animals , Male , Mice , Physical Conditioning, Animal/physiology , Insulin Resistance/physiology , Adiposity/physiology , Muscle Stretching Exercises/methods , Hypertrophy/physiopathology , Inflammation/physiopathology , Obesity/physiopathology , Time Factors , Blood Glucose/analysis , Body Weight/physiology , Enzyme-Linked Immunosorbent Assay , Reproducibility of Results , Tumor Necrosis Factor-alpha/analysis , Adipose Tissue, White/physiopathology , Resistance Training/methods , Diet, High-Fat , Mice , Mice, Obese
Biomolecules & Therapeutics ; : 107-116, 2019.
Article in English | WPRIM | ID: wpr-719634


The global obesity epidemic and associated metabolic diseases require alternative biological targets for new therapeutic strategies. In this study, we show that a phytochemical sulfuretin suppressed adipocyte differentiation of preadipocytes and administration of sulfuretin to high fat diet-fed obese mice prevented obesity and increased insulin sensitivity. These effects were associated with a suppressed expression of inflammatory markers, induced expression of adiponectin, and increased levels of phosphorylated ERK and AKT. To elucidate the molecular mechanism of sulfuretin in adipocytes, we performed microarray analysis and identified activating transcription factor 3 (Atf3) as a sulfuretin-responsive gene. Sulfuretin elevated Atf3 mRNA and protein levels in white adipose tissue and adipocytes. Consistently, deficiency of Atf3 promoted lipid accumulation and the expression of adipocyte markers. Sulfuretin’s but not resveratrol’s anti-adipogenic effects were diminished in Atf3 deficient cells, indicating that Atf3 is an essential factor in the effects of sulfuretin. These results highlight the usefulness of sulfuretin as a new anti-obesity intervention for the prevention of obesity and its associated metabolic diseases.

Animals , Mice , Activating Transcription Factor 3 , Adipocytes , Adiponectin , Adipose Tissue, White , Diet , Insulin Resistance , Metabolic Diseases , Mice, Obese , Microarray Analysis , Obesity , RNA, Messenger
Journal of Korean Medical Science ; : e266-2019.
Article in English | WPRIM | ID: wpr-765110


BACKGROUND: Apart from its blood pressure-lowering effect by blocking the renin-angiotensin-aldosterone system, telmisartan, an angiotensin II type 1 receptor blocker (ARB), exhibits various ancillary effects including cardiovascular protective effects in vitro. Nonetheless, the protective effects of telmisartan in cerebrocardiovascular diseases are somewhat variable in large-scale clinical trials. Dysregulation of endothelial nitric oxide (NO) synthase (eNOS)-derived NO contributes to the developments of various vascular diseases. Nevertheless, the direct effects of telmisartan on endothelial functions including NO production and vessel relaxation, and its action mechanism have not been fully elucidated. Here, we investigated the mechanism by which telmisartan regulates NO production and vessel relaxation in vitro and in vivo. METHODS: We measured nitrite levels in culture medium and mouse serum, and performed inhibitor studies and western blot analyses using bovine aortic endothelial cells (BAECs) and a hyperglycemic mouse model. To assess vessel reactivity, we performed acetylcholine (ACh)-induced vessel relaxation assay on isolated rat aortas. RESULTS: Telmisartan decreased NO production in normoglycemic and hyperglycemic BAECs, which was accompanied by reduced phosphorylation of eNOS at Ser¹¹⁷⁹ (p-eNOS-Ser¹¹⁷⁹). Telmisartan increased the expression of protein phosphatase 2A catalytic subunit (PP2Ac) and co-treatment with okadaic acid completely restored telmisartan-inhibited NO production and p-eNOS-Ser¹¹⁷⁹ levels. Of the ARBs tested (including losartan and fimasartan), only telmisartan decreased NO production and p-eNOS-Ser¹¹⁷⁹ levels, and enhanced PP2Ac expression. Co-treatment with GW9662 had no effect on telmisartan-induced changes. In line with in vitro observations, telmisartan reduced serum nitrite and p-eNOS-Ser¹¹⁷⁹ levels, and increased PP2Ac expression in high fat diet-fed mice. Furthermore, telmisartan attenuated ACh-induced rat aorta relaxation. CONCLUSION: We demonstrated that telmisartan inhibited NO production and vessel relaxation at least in part by PP2A-mediated eNOS-Ser¹¹⁷⁹ dephosphorylation in a peroxisome proliferator-activated receptor γ-independent manner. These results may provide a mechanism that explains the inconsistent cerebrocardiovascular protective effects of telmisartan.

Animals , Mice , Rats , Acetylcholine , Aorta , Blotting, Western , Catalytic Domain , Endothelial Cells , In Vitro Techniques , Losartan , Mice, Obese , Nitric Oxide Synthase Type III , Nitric Oxide , Okadaic Acid , Peroxisomes , Phosphorylation , Protein Phosphatase 2 , Receptor, Angiotensin, Type 1 , Relaxation , Renin-Angiotensin System , Vascular Diseases
The Korean Journal of Physiology and Pharmacology ; : 335-344, 2019.
Article in English | WPRIM | ID: wpr-761802


Obesity causes inflammation and impairs thermogenic functions in brown adipose tissue (BAT). The adipokine lipocalin 2 (LCN2) has been implicated in inflammation and obesity. Herein, we investigated the protective effects of caloric restriction (CR) on LCN2-mediated inflammation and oxidative stress in the BAT of high-fat diet (HFD)-fed mice. Mice were fed a HFD for 20 weeks and then either continued on the HFD or subjected to CR for the next 12 weeks. CR led to the browning of the white fat-like phenotype in HFD-fed mice. Increased expressions of LCN2 and its receptor in the BAT of HFD-fed mice were significantly attenuated by CR. Additionally, HFD+CR-fed mice had fewer neutrophils and macrophages expressing LCN2 and iron-positive cells than HFD-fed mice. Further, oxidative stress and mitochondrial fission induced by a HFD were also significantly attenuated by CR. Our findings indicate that the protective effects of CR on inflammation and oxidative stress in the BAT of obese mice may be associated with regulation of LCN2.

Animals , Mice , Adipokines , Adipose Tissue, Brown , Caloric Restriction , Diet, High-Fat , Inflammation , Lipocalins , Macrophages , Mice, Obese , Mitochondrial Dynamics , Neutrophils , Obesity , Oxidative Stress , Phenotype
The Korean Journal of Physiology and Pharmacology ; : 161-169, 2019.
Article in English | WPRIM | ID: wpr-761787


Fumigaclavine C (FC), an active indole alkaloid, is obtained from endophytic Aspergillus terreus (strain No. FC118) by the root of Rhizophora stylosa (Rhizophoraceae). This study is designed to evaluate whether FC has anti-adipogenic effects in 3T3-L1 adipocytes and whether it ameliorates lipid accumulation in high-fat diet (HFD)-induced obese mice. FC notably increased the levels of glycerol in the culture supernatants and markedly reduced lipid accumulation in 3T3-L1 adipocytes. FC differentially inhibited the expressions of adipogenesis-related genes, including the peroxisome proliferator-activated receptor proteins, CCAAT/enhancer-binding proteins, and sterol regulatory element-binding proteins. FC markedly reduced the expressions of lipid synthesis-related genes, such as the fatty acid binding protein, lipoprotein lipase, and fatty acid synthase. Furthermore, FC significantly increased the expressions of lipolysis-related genes, such as the hormone-sensitive lipase, Aquaporin-7, and adipose triglyceride lipase. In HFD-induced obese mice, intraperitoneal injections of FC decreased both the body weight and visceral adipose tissue weight. FC administration significantly reduced lipid accumulation. Moreover, FC could dose-dependently and differentially regulate the expressions of lipid metabolism-related transcription factors. All these data indicated that FC exhibited anti-obesity effects through modulating adipogenesis and lipolysis.

Animals , Mice , Adipocytes , Adipogenesis , Aspergillus , Body Weight , Carrier Proteins , Diet, High-Fat , Glycerol , Injections, Intraperitoneal , Intra-Abdominal Fat , Lipase , Lipolysis , Lipoprotein Lipase , Mice, Obese , Peroxisomes , Rhizophoraceae , Sterol Esterase , Transcription Factors