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J Lipid Res. 2015 Feb;56(2):304-18. doi: 10.1194/jlr.M054429. Epub 2015 Jan 2.

Hepatic oleate regulates adipose tissue lipogenesis and fatty acid oxidation.

Author information

1
Departments of Nutritional Sciences, Veterans Administration Medical Center, Madison, WI 53705.
2
Biochemistry, Veterans Administration Medical Center, Madison, WI 53705.
3
Medicine, University of Wisconsin-Madison, Madison, WI 53706 Geriatric Research, Education, and Clinical Center, Veterans Administration Medical Center, Madison, WI 53705.
4
Departments of Nutritional Sciences, Veterans Administration Medical Center, Madison, WI 53705 Biochemistry, Veterans Administration Medical Center, Madison, WI 53705.

Abstract

Hepatic steatosis is associated with detrimental metabolic phenotypes including enhanced risk for diabetes. Stearoyl-CoA desaturases (SCDs) catalyze the synthesis of MUFAs. In mice, genetic ablation of SCDs reduces hepatic de novo lipogenesis (DNL) and protects against diet-induced hepatic steatosis and adiposity. To understand the mechanism by which hepatic MUFA production influences adipose tissue stores, we created two liver-specific transgenic mouse models in the SCD1 knockout that express either human SCD5 or mouse SCD3, that synthesize oleate and palmitoleate, respectively. We demonstrate that hepatic de novo synthesized oleate, but not palmitoleate, stimulate hepatic lipid accumulation and adiposity, reversing the protective effect of the global SCD1 knockout under lipogenic conditions. Unexpectedly, the accumulation of hepatic lipid occurred without induction of the hepatic DNL program. Changes in hepatic lipid composition were reflected in plasma and in adipose tissue. Importantly, endogenously synthesized hepatic oleate was associated with suppressed DNL and fatty acid oxidation in white adipose tissue. Regression analysis revealed a strong correlation between adipose tissue lipid fuel utilization and hepatic and adipose tissue lipid storage. These data suggest an extrahepatic mechanism where endogenous hepatic oleate regulates lipid homeostasis in adipose tissues.

KEYWORDS:

de novo lipogenesis; fatty acid/desaturases; fatty acid/metabolism; lipids; liver; triglycerides; white adipose tissue; β-oxidation

PMID:
25555387
PMCID:
PMC4306685
DOI:
10.1194/jlr.M054429
[Indexed for MEDLINE]
Free PMC Article

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