Hydrogen sulfide reduces serum triglyceride by activating liver autophagy via the AMPK-mTOR pathway

2015 ◽  
Vol 309 (11) ◽  
pp. E925-E935 ◽  
Author(s):  
Li Sun ◽  
Song Zhang ◽  
Chengyuan Yu ◽  
Zhenwei Pan ◽  
Yang Liu ◽  
...  
Keyword(s):  
Hydrogen Sulfide ◽  
High Fat Diet ◽  
Serum Triglyceride ◽  
Mtor Pathway ◽  
Autophagic Flux ◽  
High Fat ◽  
Sodium Hydrosulfide ◽  
Metabolism Inhibition ◽  
Qualitative Effect ◽  
First Time

Autophagy plays an important role in liver triglyceride (TG) metabolism. Inhibition of autophagy could reduce the clearance of TG in the liver. Hydrogen sulfide (H2S) is a potent stimulator of autophagic flux. Recent studies showed H2S is protective against hypertriglyceridemia (HTG) and noalcoholic fatty liver disease (NAFLD), while the mechanism remains to be explored. Here, we tested the hypothesis that H2S reduces serum TG level and ameliorates NAFLD by stimulating liver autophagic flux by the AMPK-mTOR pathway. The level of serum H2S in patients with HTG was lower than that of control subjects. Sodium hydrosulfide (NaHS, H2S donor) markedly reduced serum TG levels of male C57BL/6 mice fed a high-fat diet (HFD), which was abolished by coadministration of chloroquine (CQ), an inhibitor of autophagic flux. In HFD mice, administration of NaSH increased the LC3BII-to-LC3BI ratio and decreased the p62 protein level. Meanwhile, NaSH increased the phosphorylation of AMPK and thus reduced the phosphorylation of mTOR in a Western blot study. In cultured LO2 cells, high-fat treatment reduced the ratio of LC3BII to LC3BI and the phosphorylation of AMPK, which were reversed by the coadministration of NaSH. Knockdown of AMPK by siRNA in LO2 cells blocked the autophagic enhancing effects of NaSH. The same qualitative effect was observed in AMPKα2−/− mice. These results for the first time demonstrated that H2S could reduce serum TG level and ameliorate NAFLD by activating liver autophagy via the AMPK-mTOR pathway.

scholarly journals Genetic Deletion of Syndecan-4 Alters Body Composition, Metabolic Phenotypes, and the Function of Metabolic Tissues in Female Mice Fed A High-Fat Diet (Running Title: Sdc4 Deficiency Affects Metabolic Phenotypes)

Nutrients ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 2810 ◽  
Author(s):  
Maria De Luca ◽  
Denise Vecchie’ ◽  
Baskaran Athmanathan ◽  
Sreejit Gopalkrishna ◽  
Jennifer A. Valcin ◽  
...  
Keyword(s):  
Insulin Sensitivity ◽  
High Fat Diet ◽  
Fatty Acid Synthase ◽  
Serum Triglyceride ◽  
Independent Study ◽  
Whole Body ◽  
Elderly Subjects ◽  
Sensitivity Index ◽  
High Fat ◽  
Metabolic Phenotypes

Syndecans are transmembrane proteoglycans that, like integrins, bind to components of the extracellular matrix. Previously, we showed significant associations of genetic variants in the Syndecan-4 (SDC4) gene with intra-abdominal fat, fasting plasma glucose levels, and insulin sensitivity index in children, and with fasting serum triglyceride levels in healthy elderly subjects. An independent study also reported a correlation between SDC4 and the risk of coronary artery disease in middle-aged patients. Here, we investigated whether deletion of Sdc4 promotes metabolic derangements associated with diet-induced obesity by feeding homozygous male and female Sdc4-deficient (Sdc4-/-) mice and their age-matched wild-type (WT) mice a high-fat diet (HFD). We found that WT and Sdc4-/- mice gained similar weight. However, while no differences were observed in males, HFD-fed female Sdc4-/- mice exhibited a higher percentage of body fat mass than controls and displayed increased levels of plasma total cholesterol, triglyceride, and glucose, as well as reduced whole-body insulin sensitivity. Additionally, they had an increased adipocyte size and macrophage infiltration in the visceral adipose tissue, and higher triglyceride and fatty acid synthase levels in the liver. Together with our previous human genetic findings, these results provide evidence of an evolutionarily conserved role of SDC4 in adiposity and its complications.

scholarly journals Effect of Soybean and Soybean Koji on Obesity and Dyslipidemia in Rats Fed a High-Fat Diet: A Comparative Study

2021 ◽  
Vol 18 (11) ◽  
pp. 6032
Author(s):  
Sihoon Park ◽  
Jae-Joon Lee ◽  
Hye-Won Shin ◽  
Sunyoon Jung ◽  
Jung-Heun Ha
Keyword(s):  
Adipose Tissue ◽  
White Adipose Tissue ◽  
High Fat Diet ◽  
Unsaturated Fatty Acids ◽  
Density Lipoprotein ◽  
Serum Triglyceride ◽  
Lipoprotein Cholesterol ◽  
Health Concern ◽  
High Fat ◽  
Cholesterol Levels

Soybean koji refers to steamed soybeans inoculated with microbial species. Soybean fermentation improves the health benefits of soybeans. Obesity is a serious health concern owing to its increasing incidence rate and high association with other metabolic diseases. Therefore, we investigated the effects of soybean and soybean koji on high-fat diet-induced obesity in rats. Five-week-old male Sprague-Dawley rats were randomly divided into four groups (n = 8/group) as follows: (1) regular diet (RD), (2) high-fat diet (HFD), (3) HFD + steamed soybean (HFD+SS), and (4) HFD + soybean koji (HFD+SK). SK contained more free amino acids and unsaturated fatty acids than SS. In a rat model of obesity, SK consumption significantly alleviated the increase in weight of white adipose tissue and mRNA expression of lipogenic genes, whereas SS consumption did not. Both SS and SK reduced serum triglyceride, total cholesterol, and low-density lipoprotein cholesterol levels, and increased high-density lipoprotein cholesterol levels. SS and SK also inhibited lipid accumulation in the liver and white adipose tissue and reduced adipocyte size. Although both SS and SK could alleviate HFD-induced dyslipidemia, SK has better anti-obesity effects than SS by regulating lipogenesis. Overall, SK is an excellent functional food that may prevent obesity.

scholarly journals Effects of Hamo NK hard capsule on experimental atherosclerosis model

2021 ◽  
Vol 141 (5) ◽  
pp. 95-103
Author(s):  
Pham Thuy Phuong ◽  
Pham Thi Van Anh ◽  
Dang Thi Thu Hien ◽  
Nguyen Trong Thong ◽  
Pham Quoc Binh
Keyword(s):  
Oral Administration ◽  
Triglyceride Level ◽  
High Fat Diet ◽  
Biochemical Parameters ◽  
Serum Triglyceride ◽  
Experimental Atherosclerosis ◽  
Serum Triglyceride Level ◽  
High Fat ◽  
Blood Samples ◽  
Aortic Artery

This study evaluated the effects of Hamo NK hard capsule on athresclerosis using experimental atherosclerosis model. NewZealand White rabbits were fed a high-fat diet (HFD) containing cholesterol and peanut oil. The animals received oral administration of HFD and Hamo NK hard capsule at two doses of 0.126 and 0.378 g/kg bw/day for 8 consecutive weeks. Blood samples were collected for analyis of biochemical parameters at before treatment, week 4 and week 8. Histopathology assessments of the aortic artery and liver were carried out at the end of the experiment. Hamo NK was effective in reducing serum triglyceride level after 8 weeks of the experiment. In addition, Hamo NK at two doses of 0.126 g/kg b.w and 0.378 g/kg b.w for 8 consecutive weeks did not affect the cholesterol, LDL-C and HDL-C concentrations induced by a HFD. Hamo NK at the dose of 0.126 g/kg bw/day was not only able to decrease significant aortic surface lesions but also capable of managing atherosclerosis plaques formation in aorta; whereas theses activities were not notiaceable at the dose of 0.378 g/kg b.w.

PDGF-D activation by macrophage-derived uPA promotes AngII-induced cardiac remodeling in obese mice

2021 ◽  
Vol 218 (9) ◽  
Author(s):  
Yu-Wen Cheng ◽  
Ze-Bei Zhang ◽  
Bei-Di Lan ◽  
Jing-Rong Lin ◽  
Xiao-Hui Chen ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Adipose Tissue ◽  
Cardiac Remodeling ◽  
High Fat Diet ◽  
Platelet Derived Growth Factor ◽  
Obese Mice ◽  
Mechanistic Studies ◽  
High Fat ◽  
Cardiac Damage ◽  
First Time

Obesity-induced secretory disorder of adipose tissue–derived factors is important for cardiac damage. However, whether platelet-derived growth factor-D (PDGF-D), a newly identified adipokine, regulates cardiac remodeling in angiotensin II (AngII)–infused obese mice is unclear. Here, we found obesity induced PDGF-D expression in adipose tissue as well as more severe cardiac remodeling compared with control lean mice after AngII infusion. Adipocyte-specific PDGF-D knockout attenuated hypertensive cardiac remodeling in obese mice. Consistently, adipocyte-specific PDGF-D overexpression transgenic mice (PA-Tg) showed exacerbated cardiac remodeling after AngII infusion without high-fat diet treatment. Mechanistic studies indicated that AngII-stimulated macrophages produce urokinase plasminogen activator (uPA) that activates PDGF-D by splicing full-length PDGF-D into the active PDGF-DD. Moreover, bone marrow–specific uPA knockdown decreased active PDGF-DD levels in the heart and improved cardiac remodeling in HFD hypertensive mice. Together, our data provide for the first time a new interaction pattern between macrophage and adipocyte: that macrophage-derived uPA activates adipocyte-secreted PDGF-D, which finally accelerates AngII-induced cardiac remodeling in obese mice.

scholarly journals Perivascular fat-mediated vascular dysfunction and remodeling through the AMPK/mTOR pathway in high-fat diet-induced obese rats

2010 ◽  
Vol 33 (5) ◽  
pp. 446-453 ◽  
Author(s):  
Liqun Ma ◽  
Shuangtao Ma ◽  
Hongbo He ◽  
Dachun Yang ◽  
Xiaoping Chen ◽  
...  
Keyword(s):  
High Fat Diet ◽  
Vascular Dysfunction ◽  
Mtor Pathway ◽  
High Fat ◽  
Obese Rats ◽  
Perivascular Fat

Exercise restores bioavailability of hydrogen sulfide and promotes autophagy influx in livers of mice fed with high-fat diet

2017 ◽  
Vol 95 (6) ◽  
pp. 667-674 ◽  
Author(s):  
Bing Wang ◽  
Jing Zeng ◽  
Qi Gu
Keyword(s):  
Hydrogen Sulfide ◽  
Exercise Training ◽  
High Fat Diet ◽  
Mass Gain ◽  
Moderate Intensity ◽  
High Fat ◽  
Moderate Intensity Exercise ◽  
Nonalcoholic Fatty Liver ◽  
Mercaptopyruvate Sulfurtransferase ◽  
Underlying Mechanisms

In the gold standard treatment for nonalcoholic fatty liver disease (NAFLD), exercise training has been shown to effectively improve nonalcoholic steatohepatitis (NASH). However, limited data are available about the underlying mechanisms involved. This work was undertaken to investigate the mechanisms underlying the beneficial effect of exercise training on high-fat diet (HFD)-induced NAFLD in mice. Male mice were fed with HFD and given moderate-intensity exercise for 24 weeks. Exercise training lowered mass gain, attenuated systemic insulin resistance and glucose intolerance, and mitigated hepatic steatosis and fibrosis in mice fed with HFD. Exercise training improved mitochondrial function and enhanced mitochondrial β-oxidation in livers of HFD-fed mice. Exercise training enhanced hydrogen sulfide (H2S) levels in plasma and livers, and mRNA expression of cystathionine β-synthase (CBS), cystathionine γ-lyase (CES), and 3-mercaptopyruvate sulfurtransferase (3-MST) in livers of HFD-fed mice. Exercise training had no significant effect on the ratio of LC3-II/LC3-I, but decreased p62 protein expression in livers of HFD-fed mice. Additionally, exercise training reduced formation of malondialdehyde, enhanced ratio of GSH/GSSG, and down-regulated expression of TNF-α and IL-6 in livers of HFD-fed mice. Exercise training restored bioavailability of H2S and promoted autophagy influx in livers, which might contribute to its benefit on HFD-induced NAFLD.

scholarly journals Antioxidative Diet Supplementation Reverses High-Fat Diet-Induced Increases of Cardiovascular Risk Factors in Mice

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Hilda Vargas-Robles ◽  
Amelia Rios ◽  
Monica Arellano-Mendoza ◽  
Bruno A. Escalante ◽  
Michael Schnoor
Keyword(s):  
Oxidative Stress ◽  
Risk Factors ◽  
Cardiovascular Risk ◽  
Cardiovascular Risk Factors ◽  
High Fat Diet ◽  
Serum Triglyceride ◽  
High Fat ◽  
Daily Consumption ◽  
Beneficial Effects ◽  
Diet Supplementation

Obesity is a worldwide epidemic that is characterized not only by excessive fat deposition but also by systemic microinflammation, high oxidative stress, and increased cardiovascular risk factors. While diets enriched in natural antioxidants showed beneficial effects on oxidative stress, blood pressure, and serum lipid composition, diet supplementation with synthetic antioxidants showed contradictive results. Thus, we tested in C57Bl/6 mice whether a daily dosage of an antioxidative mixture consisting of vitamin C, vitamin E, L-arginine, eicosapentaenoic acid, and docosahexaenoic acid (corabion) would affect cardiovascular risk factors associated with obesity. Obese mice showed increased serum triglyceride and glucose levels and hypertension after eight weeks of being fed a high-fat diet (HFD). Importantly, corabion ameliorated all of these symptoms significantly. Oxidative stress and early signs of systemic microinflammation already developed after two weeks of high-fat diet and were significantly reduced by daily doses of corabion. Of note, the beneficial effects of corabion could not be observed when applying its single antioxidative components suggesting that a combination of various nutrients is required to counteract HFD-induced cardiovascular risk factors. Thus, daily consumption of corabion may be beneficial for the management of obesity-related cardiovascular complications.

scholarly journals Cancer Stem Cell Enrichment and Metabolic Substrate Adaptability are Driven by Hydrogen Sulfide Suppression in Glioblastoma

2020 ◽  
Author(s):  
Daniel J. Silver ◽  
Gustavo A. Roversi ◽  
Nazmin Bithi ◽  
Chase K. A. Neumann ◽  
Katie M. Troike ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hydrogen Sulfide ◽  
Cancer Stem Cell ◽  
High Fat Diet ◽  
Control Diet ◽  
Chemotherapy Resistance ◽  
Cellular Metabolism ◽  
Protein S ◽  
High Fat ◽  
The Impact

AbstractGlioblastoma (GBM) remains among the deadliest of human malignancies. The emergence of the cancer stem cell (CSC) phenotype represents a major challenge to disease management and durable treatment response. The extrinsic, environmental, and lifestyle factors that result in CSC enrichment are not well understood. The CSC state endows cells with a fluid metabolic profile, enabling the utilization of multiple nutrient sources. Therefore, to test the impact of diet on CSC enrichment, we evaluated disease progression in tumor-bearing mice fed an obesity-inducing high-fat diet (HFD) versus an energy-balanced, low-fat control diet. HFD consumption resulted in hyper-aggressive disease that was accompanied by CSC enrichment and shortened survival. HFD consumption also drove intracerebral accumulation of saturated fats, which in turn inhibited the production and signaling of the gasotransmitter hydrogen sulfide (H2S). H2S is an endogenously produced bio-active metabolite derived from sulfur amino acid catabolism. It functions principally through protein S-sulfhydration and regulates a variety of programs including mitochondrial bioenergetics and cellular metabolism. Inhibition of H2S synthesis resulted in increased proliferation and chemotherapy resistance, whereas treatment with H2S donors led to cytotoxicity and death of cultured GBM cells. Compared to non-cancerous controls, patient GBM specimens were reduced in overall protein S-sulfhydration, which was primarily lost from proteins regulating cellular metabolism. These findings support the hypothesis that diet-regulated H2S signaling serves to suppress GBM by restricting metabolic adaptability, while its loss triggers CSC enrichment and disease acceleration. Interventions augmenting H2S bioavailability concurrent with GBM standard of care may improve outcomes for GBM patients.One Sentence SummaryConsumption of a high-fat diet (HFD) accelerates glioblastoma (GBM) by inhibiting the production and signaling of the tumor-suppressive metabolite hydrogen sulfide (H2S).

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