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In Vitro and In Vivo Effects of Piceatannol and Resveratrol on Glucose Control and TLR4-NF-κB Pathway

피세아테놀과 레스베라트롤의 혈당조절 및 TLR4-NF-κB 경로 조절 작용

  • Lee, Hee Jae (Department of Food and Nutrition, Seoul Women's University) ;
  • Lee, Hae-Jeung (Department of Food and Nutrition, Gachon University) ;
  • Yang, Soo Jin (Department of Food and Nutrition, Seoul Women's University)
  • 이희재 (서울여자대학교 식품영양학과) ;
  • 이해정 (가천대학교 식품영양학과) ;
  • 양수진 (서울여자대학교 식품영양학과)
  • Received : 2017.01.13
  • Accepted : 2017.01.19
  • Published : 2017.02.28

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 ($NF-{\kappa}B$) 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 ($50{\mu}M$) or RSV ($50{\mu}M$). 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 $NF-{\kappa}B$ 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 $NF-{\kappa}B$ were altered in PIC-treated livers. Collectively, PIC and RSV inhibited the $TLR4-NF-{\kappa}B$ 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.

Acknowledgement

Supported by : 한국연구재단

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