Mild alcohol intake exacerbates metabolic syndrome in rodents: a putative role of GSK-3ß.

Metabolic syndrome is characterized with abdominal obesity, insulin resistance, dyslipidemia and hepatic dysfunction. Glycogen synthase kinase-3ß (GSK-3ß) expression has been observed in adipose tissues in obese and diabetic humans, and in rodents. The aim of study was to investigate role of GSK-3ß in modulation of metabolic alterations in alcoholic fed rats. Male Wistar albino rats (180-220 g) were used. High fat diet (HFD) for 8 weeks and alcohol (2%) from third to eighth week were given. Lithium chloride (LiCl), a GSK-3ß inhibitor (60 mg/kg) was used orally from third to eighth week. HFD treatment caused significant (p < 0.05) increase in the percentage of body weight gain, BMI, Lee index, different fat pads, liver weights, serum glucose, leptin, triglyceride, LDL, VLDL, cholesterol, alanine transaminase, aspartate transaminase, tissue thio-barbituric acid reactive substances, nitrate/nitrite and significant decrease in food intake (g), serum HDL and tissue GSH in HFD control rats, as compared to normal control (NC). Administration of alcohol (2%) ad libitum potentiated the effect of normal and HFD, respectively, in NC and HFD control rats, respectively. Administration of LiCl produced significant amelioration in biochemical and pathological changes caused in the form of metabolic syndrome in HFD alone and HFD and alcohol-treated rats. The histological observations also showed similar findings in liver tissue. It may be concluded that inactivation of GSK-3ß consequently leads to increased leptin and insulin sensitivity as evidenced by the reversal of alterations caused due to metabolic syndrome in rodents fed with HFD and mild alcohol.

Possible modulation of FAS and PTP-1B signaling in ameliorative potential of Bombax ceiba against high fat diet induced obesity.

BACKGROUND: Bombax ceiba Linn., commonly called as Semal, is used in various gastro-intestinal disturbances. It contains Lupeol which inhibits PTP-1B, adipogenesis, TG synthesis and accumulation of lipids in adipocytes and adipokines whereas the flavonoids isolated from B. ceiba has FAS inhibitory activity. The present study was aimed to investigate ameliorative potential of Bombax ceiba to experimental obesity in Wistar rats, and its possible mechanism of action. METHODS: Male Wistar albino rats weighing 180-220 g were employed in present study. Experimental obesity was induced by feeding high fat diet for 10 weeks. Methanolic extract of B. ceiba extract 100, 200 and 400 mg/kg and Gemfibrozil 50 mg/kg as standard drug were given orally from 7th to 10th week. RESULTS: Induction with HFD for 10 weeks caused significant (p < 0.05) increase in % body wt, BMI, LEE indices; serum glucose, triglyceride, LDL, VLDL, cholesterol, free fatty acid, ALT, AST; tissue TBARS, nitrate/nitrite levels; different fat pads and relative liver weight; and significant decrease in food intake (g and kcal), serum HDL and tissue glutathione levels in HFD control rats. Treatment with B. ceiba extract and Gemfibrozil significantly attenuated these HFD induced changes, as compared to HFD control. The effect of B. ceiba 200 and 400 mg/kg was more pronounced in comparison to Gemfibrozil. CONCLUSION: On the basis of results obtained, it may be concluded that the methanolic extract of stem bark of Bombax ceiba has significant ameliorative potential against HFD induced obesity in rats, possibly through modulation of FAS and PTP-1B signaling due to the presence of flavonoids and lupeol.