Adipose‐specific knockout of acetyl‐CoA carboxylase 1 causes growth retardation and reduced de novo fatty acid synthesis in fat tissues

Abstract

Fatty acid synthesis is essential to maintain energy homeostasis in animals. Adipose tissue is one of the major sites for de novo fatty acid synthesis and lipid storage. We generated mice with adipose‐specific inactivation of acetyl‐CoA carboxylase 1 (ACC1), the rate‐limiting enzyme in de novo fatty acid synthesis. The adipose (fat)‐specific ACC1 knockout (FACC1KO) mice were growth retarded in utero and grew more slowly than wild type (WT) mice until weaning, after which they gained weight in parallel with WT mice on a normal diet. Under lipogenic conditions, lipid accumulation in the adipose tissues of four‐month‐old FACC1KO mice was significantly decreased compared to WT mice, which is consistent with 50∼66% reduction in the ACC activity levels in these tissues. The activities of ACC and fatty acid synthase in the liver were not increased, indicating that hepatic de novo fatty acid synthesis was not changed to compensate for the reduction of ACC1 levels in the adipose tissues. Inactivation of ACC1 leads to ∼30% lower level of serum insulin‐like growth factor I (IGF‐I) compared to WT mice, which was accompanied by decreased chondrocyte proliferation in the growth plate, lower bone mineral density, and overall skeletal growth retardation of FACC1KO mice. Serum leptin level in FACC1KO mice was decreased ∼50% compared to WT mice; however, it did not counteract the osteopenic effects of IGF‐I on the bone. Although FACC1KO mice weigh less under normal diet, a high‐fat/high carbohydrate diet makes FACC1KO mice obese, just as WT mice.