AMPK activation by pterostilbene contributes to suppression of hepatic gluconeogenic gene expression and glucose production in H4IIE cells

Pterostilbene, a bioactive component of blueberries and grapes, shows structural similarity to resveratrol, and exhibits antioxidant, anti-inflammatory, anti-cancer, hypoglycemic, and cholesterol lowering effects. Recent evidence indicates that pterbstilbene is an agonist of the nuclear receptor, peroxisome proliferator-activated receptor-alpha (PVAR-alpha). Since PPAR-alpha agonists induce peroxisomal proliferation and fatty acid oxidation, we examined gene expression of acyl CoA oxidase (ACO) and carnitine palmitoyl transferase-1 (CPT-1). Pterostilbene treatment, at concentrations that demonstrated over 75% cell viability (20 mu M, 50 mu M), significantly increased gene expression of ACO, CFT-1, and PPAR-alpha. Pterostilbene treatment (50 mu M) also demonstiated potent activation of AMP-activated kinase (AMPK), compared to AICAR (0.5 mM) or metformin (2 mM), consistent with upregulation in fatty acid oxidation gene expression. Since AMPK activators mimic the actions of insulin by repressing hepatic gluconeogenesis, we examined pterostilbene's effects On hepatic gluconeogenic gene expression. Pterostilbene treatment significantly repressed dexamethasorie-induced phosphoenol pyruvate carboxykinase (PEPCK) and glucose6-phosphatase (G6Pase) gene expression, and decreased glucose production in H4IIE cells. Taken together, our studies demonstrate that ptei-ostilbene, a natural compound and PPAR-a agonist, modulate several AMPK-dependent metabolic functions. The results of the present study suggest that pterostilbene may have beneficial effects in the prevention and management of type 2 diabetes and related disorders. In this study; we found that pterostilbene activated AMP-activated kinase (AMPK) and increased the expression of fatty acid oxidation genes, including acyl CoA oxidase and carnitine palmitoyl transferase-1. (C) 2018 Elsevier Inc. All rights reserved.