Research Article Details
| Article ID: | A16788 |
| PMID: | 28177674 |
| Source: | Can J Physiol Pharmacol |
| Title: | Exercise restores bioavailability of hydrogen sulfide and promotes autophagy influx in livers of mice fed with high-fat diet. |
| Abstract: | 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. |
| DOI: | 10.1139/cjpp-2016-0611 |
| Strategy ID | Therapy Strategy | Synonyms | Therapy Targets | Therapy Drugs | |
|---|---|---|---|---|---|
| S08 | Lifestyle measures | Lifestyle intervention; weight loss; diet adaptation; dietary interventions; lifestyle modifications; Exercise | -- | -- | Details |
| S01 | Improve insulin resistance | insulin sensitizer; insulin resistance; glucose tolerance | Biguanide: increases 5-AMP activated protein kinase signaling; SGLT-2 inhibitor; Thiazalidinedione: selective PPAR-γ agonists; GLP-1 agonist | Metformin; Empagliflozin; Canagliflozin; Rosiglitazone; Pioglitazone; Liraglutide | Details |
| S03 | Anti-fibrosis | fibrosis | Angiotensin Receptor Blocker (ARB); CCR2/CCR5 antagonist; Thyroid receptor β agonist; PEGylated human FGF21 analogue; Monoclonal antibody to lysyl oxidase-like 2 (LOXL2); Galectin-3 inhibitor; FGF19 variant | Losartan; Cenicriviroc; VK-2809; MGL-3196; Pegbelfermin; Simtuzumab; GR-MD-02; NGM282 | Details |
| S04 | Anti-oxidative stress | oxidative stress | α-tocopherol: antioxidant | Vitamin E | Details |
| Diseases ID | DO ID | Disease Name | Definition | Class | |
|---|---|---|---|---|---|
| I05 | 9352 | Type 2 diabetes mellitus | A diabetes that is characterized by chronic hyperglycaemia with disturbances of carbohydrate, fat and protein metabolism resulting from defects in insulin secretion, insulin action, or both. A diabetes mellitus that is characterized by high blood sugar, insulin resistance, and relative lack of insulin. http://en.wikipedia.org/wiki/Diabetes, http://en.wikipedia.org/wiki/Diabetes_mellitus_type_2 | disease of metabolism/inherited metabolic disorder/ carbohydrate metabolic disorder/glucose metabolism disease/diabetes/ diabetes mellitus | Details |
| Drug ID | Drug Name | Type | DrugBank ID | Targets | Category | Latest Progress | |
|---|---|---|---|---|---|---|---|
| D182 | Insulin | Biological drug | DB00030 | INSR agonist; CPE modulator&product of | -- | Under clinical trials | Details |
| D158 | Glutathione | Chemical drug | DB00143 | MGST3; HPGDS; GSTM2; GSTM5; GPX7 cofactor; MGST2; GSS; GSTM1; GSTK1; GSTM3; GSTM4; GPX1 cofactor; GPX2 cofactor; GPX3 cofactor | -- | Under clinical trials | Details |