Regulation of fatty acid trafficking in liver by thioesterase superfamily member 1.
J Lipid Res
; 59(2): 368-379, 2018 02.
Article
em En
| MEDLINE
| ID: mdl-29208699
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. 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.
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1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Palmitoil-CoA Hidrolase
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Ácidos Graxos
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Fígado
Limite:
Animals
Idioma:
En
Revista:
J Lipid Res
Ano de publicação:
2018
Tipo de documento:
Article