ACC2 Is Expressed at High Levels Human White Adipose and Has an Isoform with a Novel N-Terminus

Abstract

Acetyl-CoA carboxylases ACC1 and ACC2 catalyze the carboxylation of acetyl-CoA to malonyl-CoA, regulating fatty-acid synthesis and oxidation, and are potential targets for treatment of metabolic syndrome. Expression of ACC1 in rodent lipogenic tissues and ACC2 in rodent oxidative tissues, coupled with the predicted localization of ACC2 to the mitochondrial membrane, have suggested separate functional roles for ACC1 in lipogenesis and ACC2 in fatty acid oxidation. We find, however, that human adipose tissue, unlike rodent adipose, expresses more ACC2 mRNA relative to the oxidative tissues muscle and heart. Human adipose, along with human liver, expresses more ACC2 than ACC1. Using RT-PCR, real-time PCR, and immunoprecipitation we report a novel isoform of ACC2 (ACC2.v2) that is expressed at significant levels in human adipose. The protein generated by this isoform has enzymatic activity, is endogenously expressed in adipose, and lacks the N-terminal sequence. Both ACC2 isoforms are capable of de novo lipogenesis, suggesting that ACC2, in addition to ACC1, may play a role in lipogenesis. The results demonstrate a significant difference in ACC expression between human and rodents, which may introduce difficulties for the use of rodent models for development of ACC inhibitors.

Combination of lipid metabolism alterations and their sensitivity to inflammatory cytokines in human lipin-1-deficient myoblasts

“…Primary antibodies (Lipin-1 (RD, AF3885), lipin-2 (Santa Cruz, sc-134433), ACACB (Cell signal Technology, 3662) [24], Malonyldecarboxylase (abcdm, ab95945) and β-Actin (Santa cruz, sc-81178)) were detected by appropriate HRP-conjugated secondary antibody followed by ECL detection.…”

Closer association of mitochondria with lipid droplets in hepatocytes and activation of Kupffer cells in resveratrol-treated senescence-accelerated mice

“…2e). Acetyl-CoA carboxylase (ACC) enhances fatty acid synthesis or lipogenesis (Castle et al 2009;Harada et al 2007), and phosphorylating this enzyme inhibits its function, reducing synthesis and enhancing the oxidation of fatty acids (Dasgupta and Milbrandt 2007;Harada et al 2007). We assessed the phosphorylation level of ACC and found that it signiWcantly increased with resveratrol treatment (Fig.…”

ACC2 gene polymorphisms, metabolic syndrome, and gene-nutrient interactions with dietary fat

“…Much of the work on ACC to date has focused on animal studies, where cellular distribution of ACC and mRNA tissue expression patterns suggested separate functional roles for ACC1 and ACC2 ( 1,(6)(7)(8)(9). However, recent examination of human ACC expression indicates greater expression of ACC2 in both oxidative and lipogenic tissues ( 10 ).…”

“…Nevertheless, work by Pape et al demonstrated that starvation and diabetes reduced ACC mRNA as well as ACC activity (i.e., changes in the level of mRNA correspond to changes in the activity and amount of acetyl-CoA carboxylase), leading the authors to conclude that physiological conditions that affect fatty acid synthesis do so, in part, by modulating ACC gene expression ( 45 ). More recently Castle et al demonstrated that overexpression of ACC2 isoforms [the usual ACC2v.1 and a novel isoform (ACC2.v2)] increase ACC2 enzymatic activity to a similar extent, indicating that changes at the protein level translate to alterations in activity ( 10 ). It is also possible that this SNP may be a surrogate marker for other functional SNPs of ACC2 or other genes in the region.…”