In vitro and in vivo effects of piceatannol and resveratrol on glucose control and TLR4-NF-κB pathway

Abstract

Piceatannol (PIC) is a natural hydroxylated analog of resveratrol (RSV), which is a polyphenol known to extend lifespan by stimulating sirtuins. The aim of this study was to investigate the effects of PIC and RSV on the toll-like receptor 4 (TLR4)-nuclear factor kappa B (NF-κB) pathway in mouse hepatocytes and an obese/diabetic KK/HlJ mouse model. AML12 mouse hepatocytes in the absence or presence of palmitic acids (PA) were treated with PIC (50 μM) or RSV (50 μM). Male KK/HlJ mice at 20 weeks of age were divided into three subgroups as follows: 1) obese and diabetic control (KK), 2) KK_PIC, and 3) KK_RSV. PIC and RSV were administered orally at a dose of 10 mg/kg/d for 4 weeks. Four weeks of PIC and RSV treatment did not affect body weight or food intake in KK mice. Serum fasting blood glucose was significantly reduced in KK_PIC, and 2 h oral glucose tolerance test area under the curve was significantly reduced by PIC and RSV treatment in KK mice. PIC tended to improve homeostasis model assessment of the insulin resistance index (HOMA-IR) and HOMA beta-cells in diabetic KK mice. TLR4 and NF-κB were down-regulated by PIC and RSV treatments in hepatocytes in the absence or presence of PA. Insulin receptor, AMP-activated protein kinase, peroxisome proliferator-activated receptor gamma, nucleotide oligomerization domain-like receptor family pyrin domain-containing 3, interleukin-1, and NF-κB were altered in PIC-treated livers. Collectively, PIC and RSV inhibited the TLR4-NF-κB pathway, and PIC seems to be more effective than RSV in the regulation of analyzed targets, which are involved in insulin signaling and inflammation in vivo. © 2017, Korean Society of Food Science and Nutrition. All rights reserved.