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Possible involvement and the mechanisms of excess trans-fatty acid consumption in severe NAFLD in mice.

Abstract：

BACKGROUND & AIMS:Excessive trans-fatty acids (TFA) consumption has been thought to be a risk factor mainly for coronary artery diseases while less attention has been paid to liver disease. We aimed to clarify the impact of TFA-rich oil consumption on the hepatic pathophysiology compared to natural oil. METHODS:Mice were fed either a low-fat (LF) or high-fat (HF) diet made of either natural oil as control (LF-C or HF-C) or partially hydrogenated oil, TFA-rich oil (LF-T or HF-T) for 24 weeks. We evaluated the liver and body weight, serological features, liver lipid content and composition, liver histology and hepatic lipid metabolism-related gene expression profile. In addition, primary cultures of mice Kupffer cells (KCs) were evaluated for cytokine secretion and phagocytotic ability after incubation in cis- or trans-fatty acid-containing medium. RESULTS:The HF-T-fed mice showed significant increases of the liver and body weights, plasma alanine-aminotransferase, free fatty acid and hepatic triglyceride content compared to the HF-C group, whereas the LF-T group did not differ from the LF-C group. HF-T-fed mice developed severe steatosis, along with increased lipogenic gene expression and hepatic TFA accumulation. KCs showed increased tumor necrosis factor secretion and attenuated phagocytotic ability in the TFA-containing medium compared to its cis-isomer. CONCLUSIONS:Excessive consumption of the TFA-rich oil up-regulated the lipogenic gene expression along with marked hepatic lipid accumulation. TFA might be pathogenic through causing severe steatosis and modulating the function of KCs. The quantity and composition of dietary lipids could be responsible for the pathogenesis of non-alcoholic steatohepatitis.

journal_name

J Hepatol

journal_title

Journal of hepatology

authors

Obara N,Fukushima K,Ueno Y,Wakui Y,Kimura O,Tamai K,Kakazu E,Inoue J,Kondo Y,Ogawa N,Sato K,Tsuduki T,Ishida K,Shimosegawa T

doi

10.1016/j.jhep.2010.02.029

subject

Has Abstract

pub_date

2010-08-01 00:00:00

pages

326-34

issue

2

eissn

0168-8278

issn

1600-0641

pii

S0168-8278(10)00270-9

journal_volume

53

pub_type

杂志文章

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