title: Involvement of SIRT1-AMPK signaling in the protective action of indole-3-carbinol against hepatic steatosis in mice fed a high-fat diet.
abstract: This study addressed the effect of indole-3-carbinol (I3C) supplementation on hepatic steatosis in mice fed a high-fat diet (HFD) and clarified the underlying mechanism. Male C57BL/6N mice were divided into three groups: those who received a normal diet, those fed with HFD and those fed with 0.1% I3C-supplemented diet (I3CD). In the present study, an HFD supplemented with 0.1% I3C significantly decreased body and liver weight as well as plasma and hepatic lipid levels. The activation of the silent mating type information regulation 2 homolog 1 (SIRT1)-AMP-activated protein kinase (AMPK) signaling system by I3C correlated with decreased mRNA levels of sterol regulatory element-binding protein-1c-regulated lipogenic enzymes. In addition, I3C significantly reversed HFD-induced up-regulation of ER stress-mediated signaling molecules in the liver, which may have contributed to the protective effects of I3C against hepatic steatosis. Furthermore, HFD-induced up-regulations of inflammatory genes such as tumor necrosis factor α and interleukin 6 were significantly reversed by dietary I3C supplementation. Our study suggests that the protective action of I3C against hepatic steatosis is mediated, at least in part, through the up-regulation of a SIRT1-AMPK signaling system in the livers of HFD-fed mice. Further investigations revealed that alleviation of the ER stress response represented a critical mechanism underlying the beneficial effects of I3C on hepatic steatosis.
authors: Taesun Park, Department of Food and Nutrition, Yonsei University, Seoul 120-749, Republic of Korea.
authors: Youngshim
authors: Y
authors: Choi
authors: Yasuko
authors: Y
authors: Yanagawa
authors: Soyoung
authors: S
authors: Kim
authors: Taesun
authors: T
authors: Park
mesh_terms: D000263:Adenylate Kinase / Q000378:metabolism*; D000818:Animals; D001483:Base Sequence; D017931:DNA Primers; D004041:Dietary Fats / Q000008:administration & dosage*; D004721:Endoplasmic Reticulum / Q000378:metabolism; D005234:Fatty Liver / Q000517:prevention & control*; D007211:Indoles / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016133:Polymerase Chain Reaction; D015398:Signal Transduction; D056564:Sirtuin 1 / Q000378:metabolism*
chemical_list: D017931:DNA Primers; D004041:Dietary Fats; D007211:Indoles; C016517:indole-3-carbinol; D000263:Adenylate Kinase; C470545:Sirt1 protein, mouse; D056564:Sirtuin 1