Regulation of fatty acid trafficking in liver by thioesterase superfamily member 1

Journal of Lipid Research

Michele Alves-Bezerra¹  Cafer Ozdemir¹  Yue Li¹  Susan J. Hagen²  Curtis J. Bare³  David E. Cohen³  Yingxia Li³  Anal Desai³ 

[1] Sanford I. Weill Department of Medicine, Weill Cornell Medical College, New York, NY 10021;Department of Biochemistry, Boston University School of Medicine, Boston, MA 02118;;Joan &

关键词: lipids;    nonalcoholic fatty liver disease;    obesity;    triglycerides;    fatty acid/metabolism;    fatty acid/oxidation;   

DOI  :  

来源: DOAJ

【 摘 要 】

Thioesterase superfamily member 1 (Them1) is an acyl-CoA thioesterase that is highly expressed in brown adipose tissue, where it functions to suppress energy expenditure. Lower Them1 expression levels in the liver are upregulated in response to high-fat feeding. Them1−/− mice are resistant to diet-induced obesity, hepatic steatosis, and glucose intolerance, but the contribution of Them1 in liver is unclear. To examine its liver-specific functions, we created conditional transgenic mice, which, when bred to Them1−/− mice and activated, expressed Them1 exclusively in the liver. Mice with liver-specific Them1 expression exhibited no changes in energy expenditure. Rates of fatty acid oxidation were increased, whereas hepatic VLDL triglyceride secretion rates were decreased by hepatic Them1 expression. When fed a high-fat diet, Them1 expression in liver promoted excess steatosis in the setting of reduced rates of fatty acid oxidation and preserved glycerolipid synthesis. Liver-specific Them1 expression did not influence glucose tolerance or insulin sensitivity, but did promote hepatic gluconeogenesis in high-fat-fed animals. This was attributable to the generation of excess fatty acids, which activated PPARα and promoted expression of gluconeogenic genes. These findings reveal a regulatory role for Them1 in hepatocellular fatty acid trafficking.

【 授权许可】

Unknown