Research Article Details
| Article ID: | A19058 |
| PMID: | 26794005 |
| Source: | J Gastroenterol |
| Title: | Pu-erh tea extract ameliorates high-fat diet-induced nonalcoholic steatohepatitis and insulin resistance by modulating hepatic IL-6/STAT3 signaling in mice. |
| Abstract: | BACKGROUND: Pu-erh tea, made from the leaves of Camellia sinensis, possesses activities beneficial for human health, including anti-inflammatory, anti-oxidant, and anti-obesity properties. OBJECTIVE: We investigated the effects of a pu-erh tea extract (PTE) on nonalcoholic steatohepatitis (NASH) and the molecular mechanisms underlying such effects. METHODS: Eight-week-old male C57BL/6J mice were fed a normal chow diet or high-fat diet (HFD) for 17 weeks, during which PTE was simultaneously administered in drinking water. Body weight, hepatic inflammation, steatosis, insulin sensitivity, expression of lipogenesis- and gluconeogenesis-associated genes, and signal transducer and activator of transcription (STAT)-3 phosphorylation were examined. The anti-steatotic effects of PTE and/or interleukin (IL)-6 were evaluated in HepG2 cells. The lipid accumulation, STAT3 phosphorylation, and expression of lipid metabolism-related genes were analyzed. RESULTS: PTE inhibited HFD-induced obesity and significantly attenuated HFD-induced hepatic steatosis and liver inflammation, and prevented against liver injury. PTE treatment improved glucose tolerance and insulin sensitivity in HFD-fed mice. Moreover, PTE treatment maintained the intact insulin signal and significantly decreased expression of gluconeogenesis-related genes in the livers of HFD-fed mice. PTE treatment strikingly enhanced STAT3 phosphorylation in the livers of HFD-fed mice. Consistent with this increase in STAT3 phosphorylation, pre-treatment of HepG2 cells with PTE enhanced IL-6-induced STAT3 phosphorylation and attenuated oleic acid-induced steatosis in a STAT3-dependent manner. In contrast, PTE inhibited IL-6-induced STAT3 phosphorylation in macrophages. CONCLUSIONS: PTE ameliorates hepatic lipid metabolism, inflammation, and insulin resistance in mice with HFD-induced NASH, presumably by modulating hepatic IL-6/STAT3 signaling. |
| DOI: | 10.1007/s00535-015-1154-0 |
| Strategy ID | Therapy Strategy | Synonyms | Therapy Targets | Therapy Drugs | |
|---|---|---|---|---|---|
| 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 |
| S02 | Enhance lipid metabolism | triglyceride-lowering; lipid tolerance; lipid metabolism | 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) inhibitor; Decreases intestinal cholesterol absorption; FXR agonist; ACC inhibitor; FAS inhibitor; DGAT2 inhibitor; SCD-1 inhibitor | Atorvastatin; Ezetimibe; Obeticholic Acid; GS-9674; GS-0976; TVB-2640; IONIS-DGAT2rx; Aramchol; | Details |
| S05 | Anti-inflammatory | inflammatory | Bile acid; TNF-a inhibitor; Dual PPAR-α and -δ agonists; Toll-Like Receptor; (TLR)-4 antagonist; Caspase inhibitor; ASK-1 inhibitor | Ursodeoxycholic Acid; Pentoxifylline; Elafibranor; JKB-121; Emricasan; Selonsertib; | Details |
| S07 | Anti-lipogenesis | de novo lipogenesis; de novo lipogenesis; DNL; anti-lipogenic mechanisms; adipogenesis; anti-obesity | stearoyl-CoA desaturase 1 (SCD-1); Acetyl-coenzyme carboxylase; acyl-CoA carboxylase inhibitor (ACC inhibitor); stearoyl Coenzyme A desaturase inhibitor (SCD inhibitor); THR-beta selective agonist; DGAT2 inhibitor; FASN inhibitor | Aramchol; Firsocostat (GS-0976); VK-2809; ION 224 | 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 |
| I14 | 9970 | Obesity | An overnutrition that is characterized by excess body fat, traditionally defined as an elevated ratio of weight to height (specifically 30 kilograms per meter squared), has_material_basis_in a multifactorial etiology related to excess nutrition intake, decreased caloric utilization, and genetic susceptibility, and possibly medications and certain disorders of metabolism, endocrine function, and mental illness. https://en.wikipedia.org/wiki/Obesity | disease of metabolism/acquired metabolic disease/ nutrition disease/overnutrition | Details |