title: Hepatic oleate regulates adipose tissue lipogenesis and fatty acid oxidation.
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.
authors.affiliation: Departments of Nutritional Sciences, Veterans Administration Medical Center, Madison, WI 53705.
authors.forename: Maggie S
authors.initials: MS
authors.lastname: Burhans
authors.affiliation: Biochemistry, Veterans Administration Medical Center, Madison, WI 53705.
authors.forename: Matthew T
authors.initials: MT
authors.lastname: Flowers
authors.affiliation: Biochemistry, Veterans Administration Medical Center, Madison, WI 53705.
authors.forename: Kristin R
authors.initials: KR
authors.lastname: Harrington
authors.affiliation: Biochemistry, Veterans Administration Medical Center, Madison, WI 53705.
authors.forename: Laura M
authors.initials: LM
authors.lastname: Bond
authors.affiliation: Biochemistry, Veterans Administration Medical Center, Madison, WI 53705.
authors.forename: Chang-An
authors.initials: CA
authors.lastname: Guo
authors.affiliation: Medicine, University of Wisconsin-Madison, Madison, WI 53706 Geriatric Research, Education, and Clinical Center, Veterans Administration Medical Center, Madison, WI 53705.
authors.forename: Rozalyn M
authors.initials: RM
authors.lastname: Anderson
authors.affiliation: Departments of Nutritional Sciences, Veterans Administration Medical Center, Madison, WI 53705 Biochemistry, Veterans Administration Medical Center, Madison, WI 53705.
authors.forename: James M
authors.initials: JM
authors.lastname: Ntambi
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism; D052436:Adipose Tissue, White / Q000378:metabolism; D000818:Animals; D005227:Fatty Acids / Q000378:metabolism*; D005260:Female; D006801:Humans; D050356:Lipid Metabolism / Q000235:genetics / Q000502:physiology; D050155:Lipogenesis / Q000235:genetics / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010084:Oxidation-Reduction; D013230:Stearoyl-CoA Desaturase / Q000235:genetics / Q000378:metabolism*; D014280:Triglycerides / Q000378:metabolism
chemical_list: D005227:Fatty Acids; D014280:Triglycerides; C502659:SCD5 protein, human; C490333:Scd1 protein, mouse; D013230:Stearoyl-CoA Desaturase
keywords: de novo lipogenesis; fatty acid/desaturases; fatty acid/metabolism; lipids; liver; triglycerides; white adipose tissue; β-oxidation