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

TitleRegulation of fatty acid trafficking in liver by thioesterase superfamily member 1.
Publication TypeJournal Article
Year of Publication2018
AuthorsDesai A, Alves-Bezerra M, Ozdemir C, Bare CJ, Li Y, Hagen SJ, Cohen DE
JournalJ Lipid Res
Volume59
Issue2
Pagination368-379
Date Published2018 Feb
ISSN1539-7262
Abstract

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. 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 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 PPARĪ± and promoted expression of gluconeogenic genes. These findings reveal a regulatory role for Them1 in hepatocellular fatty acid trafficking.

DOI10.1194/jlr.M081455
Alternate JournalJ. Lipid Res.
PubMed ID29208699
PubMed Central IDPMC5794430
Grant ListP30 DK034854 / DK / NIDDK NIH HHS / United States
R01 DK056626 / DK / NIDDK NIH HHS / United States
R01 DK103046 / DK / NIDDK NIH HHS / United States