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Ezetimibe prevents hepatic steatosis induced by a high-fat but not a high-fructose diet

Published on Jul 15, 2013in American Journal of Physiology-endocrinology and Metabolism4.13
· DOI :10.1152/ajpendo.00442.2012
Masateru Ushio1
Estimated H-index: 1
(Shiga University of Medical Science),
Yoshihiko Nishio39
Estimated H-index: 39
(Kadai: Kagoshima University)
+ 8 AuthorsHiroshi Maegawa46
Estimated H-index: 46
(Shiga University of Medical Science)
Abstract
Nonalcoholic fatty liver disease is the most frequent liver disease. Ezetimibe, an inhibitor of intestinal cholesterol absorption, has been reported to ameliorate hepatic steatosis in human and animal models. To explore how ezetimibe reduces hepatic steatosis, we investigated the effects of ezetimibe on the expression of lipogenic enzymes and intestinal lipid metabolism in mice fed a high-fat or a high-fructose diet. CBA/JN mice were fed a high-fat diet or a high-fructose diet for 8 wk with or without ezetimibe. High-fat diet induced hepatic steatosis accompanied by hyperinsulinemia. Treatment with ezetimibe reduced hepatic steatosis, insulin levels, and glucose production from pyruvate in mice fed the high-fat diet, suggesting a reduction of insulin resistance in the liver. In the intestinal analysis, ezetimibe reduced the expression of fatty acid transfer protein-4 and apoB-48 in mice fed the high-fat diet. However, treatment with ezetimibe did not prevent hepatic steatosis, hyperinsulinemia, and intestinal apoB-48 expression in mice fed the high-fructose diet. Ezetimibe decreased liver X receptor-α binding to the sterol regulatory element-binding protein-1c promoter but not expression of carbohydrate response element-binding protein and fatty acid synthase in mice fed the high-fructose diet, suggesting that ezetimibe did not reduce hepatic lipogenesis induced by the high-fructose diet. Elevation of hepatic and intestinal lipogenesis in mice fed a high-fructose diet may partly explain the differences in the effect of ezetimibe.
  • References (46)
  • Citations (24)
References46
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#1Tomonori Muraoka (YCU: Yokohama City University)H-Index: 4
#2Kazutaka Aoki (YCU: Yokohama City University)H-Index: 15
Last.Takashi Kadowaki (UTokyo: University of Tokyo)H-Index: 121
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#1Jung Sub LimH-Index: 1
#2Michele Mietus-Snyder (UCSF: University of California, San Francisco)H-Index: 20
Last.Robert H. Lustig (UCSF: University of California, San Francisco)H-Index: 56
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#2Jeong Su Park (Yonsei University)H-Index: 7
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#1Bo Li (Zhejiang University of Technology)
#2Shan-Shan Lei (Zhejiang University of Technology)H-Index: 1
Last.He Li (Zhejiang University of Technology)
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#1Jen Chieh Chuang (UTSW: University of Texas Southwestern Medical Center)H-Index: 16
#2Adam M. Lopez (UTSW: University of Texas Southwestern Medical Center)H-Index: 6
Last.Stephen D. TurleyH-Index: 28
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View next paperEzetimibe prevents the development of non‑alcoholic fatty liver disease induced by high‑fat diet in C57BL/6J mice.