Pterostilbene reverses palmitic acid mediated insulin resistance in HepG2 cells by reducing oxidative stress and triglyceride accumulation.

In this study, we evaluated ability of Pterostilbene (PTS), a methoxylated analog of resveratrol and a known antioxidant, to reverse palmitic acid (PA)-mediated IR in HepG2 cells. PTS prevented ROS formation and subsequent oxidative lipid damage by reducing the expression of NADPH oxidase 3 (NOX3) in PA treated HepG2 cells. Hepatic glucose production was used as a measure of IR and PTS reversed PA-mediated increase in hepatic glucose production by reducing expression of genes coding for gluconeogenic enzymes namely glucose-6-phosphatase (G6Pase), phosphoenolpyruvate carboxykinase (PEPCK) and pyruvate carboxylase (PC); and their transcription factors cAMP response element binding protein (CREB) and fork head class Box O (FOXO1) along with its coactivator peroxisome proliferator-activated receptor gamma co-activator-1 α (PGC1α). PTS reversed PA- mediated activation of c-jun N-terminal kinase (JNK), which in turn altered insulin signaling pathway by phosphorylating IRS-1 at Ser 307, leading to inhibition of phosphorylation of Akt and GSK-3β. PTS also reduced PA-mediated lipid accumulation by reducing expression of transcription factors SREBP1c and PPARα. SREBP1c activates genes involved in fatty acid and triglyceride synthesis while PPARα activates CPT1, a rate limiting enzyme for controlling entry and oxidation of fatty acids into mitochondria. PTS, however, did not influence PA uptake confirmed by using BODIPY-labeled fluorescent C16 fatty acid analog. Thus, our data prov...
Source: Free Radical Research - Category: Research Tags: Free Radic Res Source Type: research