Involvement of SIRT1-AMPK signaling in the protective action of indole-3-carbinol against hepatic steatosis in mice fed a high-fat diet

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• 作者：Youngshim Choi ; Yasuko Yanagawa ; Soyoung Kim ; Taesun Park ; ^{tspark@yonsei.ac.kr}
• 关键词：I3C ; indole-3-carbinol ; HFD ; high-fat diet ; ND ; normal diet ; SREBP-1c ; sterol regulatory element-binding protein-1c ; FAS ; fatty acid synthase ; LPL ; lipoprotein lipase ; SIRT1 ; silent mating type information regulation 2 homolog 1 ; AMPK ; AMP-activated prote
• 刊名：Journal of Nutritional Biochemistry
• 出版年：2013
• 出版时间：July, 2013
• 年：2013
• 卷：24
• 期：7
• 页码：1393-1400
• 全文大小：1505 K

文摘

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 ¦Á 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.