Preventive effects of bitter melon (Momordica charantia) against insulin resistance and diabetes are associated with the inhibition of NF-κB and JNK pathways in high-fat-fed OLETF rats.

Bitter melon (BM; Momordica charantia) has been used as a treatment method for various diseases including cancer and diabetes. The objective of this study was to investigate whether BM has preventive effects against insulin resistance and diabetes and to identify the underlying mechanism by which BM ameliorates insulin resistance in obese and diabetic rats. The rats were separated into three groups as follows: (a) high-fat (HF) diet control, (b) HF diet and 1% BM and (c) HF diet and 3% BM. After 6 weeks of assigned treatments, body weight and food intake were not altered by BM administration. Bitter melon treatment significantly improved glucose tolerance and insulin sensitivity. The levels of proinflammatory cytokines were significantly down-regulated in liver, muscle and epididymal fats from BM-treated rats. The activation of nuclear factor-κB (NF-κB) in the liver and muscle was decreased by BM compared with HF controls. The 3% BM supplementation significantly increased the levels of phospho-insulin receptor substrate-1 (Tyr612) and phospho-Akt (Ser473). It also significantly decreased the levels of phospho-NF-κB (p65) (Ser536) and phospho-c-Jun N-terminal kinase (JNK) (Thr183/Tyr185) in liver, muscle and epididymal fats. The findings of this study indicate that BM exerted preventive effects against insulin resistance and diabetes through the modulation of NF-κB and JNK pathways. Therefore, BM may be useful in the prevention of insulin resistance and diabetes.

Activation of peroxisome proliferator-activated receptor gamma by rosiglitazone increases sirt6 expression and ameliorates hepatic steatosis in rats.

BACKGROUND: Sirt6 has been implicated in the regulation of hepatic lipid metabolism and the development of hepatic steatosis. The aim of this study was to address the potential role of Sirt6 in the protective effects of rosiglitazone (RGZ) on hepatic steatosis. METHODS: To investigate the effect of RGZ on hepatic steatosis, rats were treated with RGZ (4 mg·kg⁻¹·day⁻¹) by stomach gavage for 6 weeks. The involvement of Sirt6 in the RGZ's regulation was evaluated by Sirt6 knockdown in AML12 mouse hepatocytes. RESULTS: RGZ treatment ameliorated hepatic lipid accumulation and increased expression of Sirt6, peroxisome proliferator-activated receptor gamma coactivtor-1-α (Ppargc1a/PGC1-α) and Forkhead box O1 (Foxo1) in rat livers. AMP-activated protein kinase (AMPK) phosphorylation was also increased by RGZ, accompanied by alterations in phosphorylation of LKB1. Interestingly, in free fatty acid-treated cells, Sirt6 knockdown increased hepatocyte lipid accumulation measured as increased triglyceride contents (p = 0.035), suggesting that Sirt6 may be beneficial in reducing hepatic fat accumulation. In addition, Sirt6 knockdown abolished the effects of RGZ on hepatocyte fat accumulation, mRNA and protein expression of Ppargc1a/PGC1-α and Foxo1, and phosphorylation levels of LKB1 and AMPK, suggesting that Sirt6 is involved in RGZ-mediated metabolic effects. CONCLUSION: Our results demonstrate that RGZ significantly decreased hepatic lipid accumulation, and that this process appeared to be mediated by the activation of the Sirt6-AMPK pathway. We propose Sirt6 as a possible therapeutic target for hepatic steatosis.