Madhuca-longifolia-hydro-ethanolic-fraction reverses mitochondrial dysfunction and modulates selective GLUT expression in diabetic mice fed with high-fat-diet

Abstract

Abstract Metabolic disorders are characterized by chronic mild inflammation that elevates circulatory inflammatory markers. The proposed hypothesis behind this includes the occurrence of mitochondrial dysfunction, oxidative stress, and hypoxia due to a high-fat diet (HFD). In the present study, the effect of madhuca-longifolia-hydro-ethanolic-fraction (MLHEF) on HFD-induced obesity and diabetes through mitochondrial action and selective GLUT expression was studied. In this study, it was observed that chronic administration of HFD (50% of diet) aggravated metabolic problems by reducing ATP production, imbalanced oxidative stress, and altered GLUT expression. Chronic HFD administration significantly reduced (p < 0.001) the superoxide dismutase (SOD) and catalase (CAT) levels, as well as elevated the liver function markers aspartate aminotransferase (AST) and alanine aminotransferase (ALT). MLHEF administration reduces oxidative stress. HFD administration also decreased the ATP/ADP ratio owing to mitochondrial dysfunction and elevated lactose dehydrogenase (LDH) levels. This imbalance leads to altered GLUT expression in hepatocytes, skeletal muscles, and adipose tissue. HFD significantly (p < 0.001) upregulated in the GLUT 1 and 3 expression while significant downregulation (p < 0.001) was observed in GLUT 2 and 4 expression in the liver, skeletal muscles, and adipose tissue. Administration of MLHEF significantly (p < 0.001) reduced LDH levels and mitochondrial dysfunction. The imbalance in GLUT levels was significantly reversed to maintain GLUT expression in tissues following MLHEF administration.