RESUMEN
Insulin resistance in Type 2 diabetes leads to hepatic steatosis that can accompanied by progressive inflammation of the liver. Citrus unshiu peel is a rich source of citrus flavonoids that possess anti-inflammatory, anti-diabetic and lipid-lowering effects. However, the ability of citrus unshiu peel ethanol extract (CPE) to improve hyperglycemia, adiposity and hepatic steatosis in Type 2 diabetes is unknown. Thus, we evaluated the effects of CPE on markers for glucose, lipid metabolism and inflammation in Type 2 diabetic mice. Male C57BL/KsJ-db/db mice were fed a normal diet with CPE (2 g/100 g diet) or rosiglitazone (0.001 g/100 g diet) for 6 weeks. Mice supplemented with the CPE showed a significant decrease in body weight gain, body fat mass and blood glucose level. The antihyperglycemic effect of CPE appeared to be partially mediated through the inhibition of hepatic gluconeogenic phosphoenolpyruvate carboxykinase mRNA expression and its activity and through the induction of insulin/glucagon secretion. CPE also ameliorated hepatic steatosis and hypertriglyceridemia via the inhibition of gene expression and activities of the lipogenic enzymes and the activation of fatty acid oxidation in the liver. These beneficial effects of CPE may be related to increased levels of anti-inflammatory adiponectin and interleukin (IL)-10, and decreased levels of pro-inflammatory markers (IL-6, monocyte chemotactic protein-1, interferon-γ and tumor necrosis factor-α) in the plasma or liver. Taken together, we suggest that CPE has the potential to improve both hyperglycemia and hepatic steatosis in Type 2 diabetes.
Asunto(s)
Citrus/química , Hígado Graso/tratamiento farmacológico , Hiperglucemia/tratamiento farmacológico , Extractos Vegetales/farmacología , Tejido Adiposo/efectos de los fármacos , Animales , Glucemia/metabolismo , Diabetes Mellitus Experimental/tratamiento farmacológico , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Enzimas/genética , Enzimas/metabolismo , Hígado Graso/metabolismo , Regulación de la Expresión Génica/efectos de los fármacos , Glucógeno/metabolismo , Hiperglucemia/metabolismo , Inflamación/tratamiento farmacológico , Inflamación/metabolismo , Metabolismo de los Lípidos/efectos de los fármacos , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Mutantes , Fosfoenolpiruvato Carboxiquinasa (ATP)/genética , Aumento de Peso/efectos de los fármacosRESUMEN
This study investigated the influence of polyphenol-rich grape skin extract (GSE) on adiposity and hepatic steatosis in mice fed a high fat diet (HFD) and its underlying mechanisms based on adipose and hepatic lipid metabolism. C57BL/6J mice were fed a normal diet or a HFD (20% fat, w/w) with or without GSE (0.15%, w/w) for 10 weeks. The supplementation of GSE significantly lowered body weight, fat weight, plasma free fatty acid level, and hepatic lipid accumulation compared to the HFD group. Plasma leptin level was significantly lower, while the plasma adiponectin level was higher in the GSE group than in the HFD group. GSE supplementation significantly suppressed the activities of lipogenic enzymes in both adipose and liver tissues, which was concomitant with ß-oxidation activation. Furthermore, GSE reversed the HFD-induced changes of the expression of genes involved in lipogenesis and ß-oxidation in the liver. These findings suggest that GSE may protect against diet-induced adiposity and hepatic steatosis by regulating mRNA expression and/or activities of enzymes that regulate lipogenesis and fatty acid oxidation in the adipose tissue and liver.