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Adipocyte Ablation of Long‐Chain Acyl‐CoA Synthetase‐4 (ACSL4) Protects Against Diet‐Induced Obesity
Author(s) -
Killion Elizabeth,
Lee MiJeong,
Coleman Rosalind,
Greenberg Andrew
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.743.1
Subject(s) - lipolysis , medicine , adipocyte , endocrinology , biology , adiponectin , insulin resistance , chemistry , insulin , adipose tissue
Obesity‐associated alterations in adipocyte metabolism are important to the development of metabolic disorders, including type 2 diabetes, a leading cause of chronic disease and death in the United States. Of relevance, the family of long‐chain acyl‐CoA synthetases catalyze the addition of a coenzyme‐A group to fatty acids (FA) within cells and have been hypothesized to direct FA to distinct fates within cells. Long‐chain acyl‐CoA synthetase‐4 (ACSL4) preferentially activates arachidonic acid (AA). However, the role of ACSL4 in adipocyte metabolism and its regulation of AA metabolites is unknown. To delineate the role of adipocyte ACSL4 in regulating systemic metabolism in vivo , we generated mice with adipocyte ACSL4 ablation (AdACSL4‐KO) by mating ACSL4 floxed mice (AdACSL4‐FL) to mice expressing the adiponectin‐cre transgene. At 8 weeks old, AdACSL4‐FL and AdACSL4‐KO male littermates were place on a low fat (LFD) or high fat diet (HFD) for 12 weeks. Body weight and fat mass were not different between AdACSL4‐FL and AdACSL4‐KO on LFD, but on HFD, AdACSL4‐KO mice have 34% less fat mass. Also on HFD, AdACSL4‐KO compared to AdACSL4‐FL demonstrated improved insulin sensitivity, smaller isolated gonadal adipocytes, higher rates of basal lipolysis, and blunted rates of isoproterenol‐stimulated lipolysis. Current studies are working to determine the mechanisms that alterations in adipocyte ACSL4 modulate obesity development and associated metabolic complications. Funding supported by NIH Training Grant #5T32DK062032‐20 and USDA #58‐1950‐7‐70.