title: aP2-Cre-mediated inactivation of acetyl-CoA carboxylase 1 causes growth retardation and reduced lipid accumulation in adipose tissues.
abstract: Adipose tissue is one of the major sites for fatty acid synthesis and lipid storage. We generated adipose (fat)-specific ACC1 knockout (FACC1KO) mice using the aP2-Cre/loxP system. FACC1KO mice showed prenatal growth retardation; after weaning, however, their weight gain was comparable to that of wild-type (WT) mice on a normal diet. Under lipogenic conditions of fasting/re-feeding a fat-free diet, lipid accumulation in adipose tissues of FACC1KO mice was significantly decreased; this is consistent with a 50-66% reduction in the ACC activity in these tissues compared with that of WT mice. Surprisingly, FACC1KO mice manifested skeletal growth retardation phenotype accompanied by decreased chondrocyte proliferation in the growth plate and lower trabecular bone density. In addition, there was about a 30% decrease in serum insulin-like growth factor I (IGF1), and while the serum leptin level was decreased by about 50%, it did not counteract the osteopenic effects of IGF1 on the bone. Fatty acid analyses of mutant bone lipids revealed relatively higher levels of C18:2n-6 and C18:3n-3 and lower levels of their elongation C20 homologs than that of WT cohorts, leading to lower levels of C20 homologs and bone development. Moreover, aP2-Cre-mediated ACC1 inactivation in bone tissue led to a decreased number of osteoblasts but not of osteoclasts. The downregulation of ACC1 on osteoblastogenesis may be the cause for the osteopenia phenotype of FACC1KO bone homeostasis.
authors.affiliation: Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
authors.forename: Jianqiang
authors.initials: J
authors.lastname: Mao
authors.forename: Tao
authors.initials: T
authors.lastname: Yang
authors.forename: Ziwei
authors.initials: Z
authors.lastname: Gu
authors.forename: William C
authors.initials: WC
authors.lastname: Heird
authors.forename: Milton J
authors.initials: MJ
authors.lastname: Finegold
authors.forename: Brendan
authors.initials: B
authors.lastname: Lee
authors.forename: Salih J
authors.initials: SJ
authors.lastname: Wakil
mesh_terms: D000103:Acetyl-CoA Carboxylase / Q000037:antagonists & inhibitors*; D000123:Acetyltransferases / Q000172:deficiency* / Q000235:genetics; D000273:Adipose Tissue / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D001851:Bone Diseases, Metabolic / Q000235:genetics; D017931:DNA Primers; D005317:Fetal Growth Retardation / Q000201:enzymology*; D006128:Growth / Q000235:genetics / Q000502:physiology; D006130:Growth Disorders / Q000139:chemically induced*; D050356:Lipid Metabolism; D008099:Liver / Q000473:pathology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D010006:Osteoblasts / Q000473:pathology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015430:Weight Gain
chemical_list: D017931:DNA Primers; D000123:Acetyltransferases; C055210:aminoglycoside N1-acetyltransferase; D000103:Acetyl-CoA Carboxylase