| First Author | Kang HW | Year | 2012 |
| Journal | FASEB J | Volume | 26 |
| Issue | 5 | Pages | 2209-21 |
| PubMed ID | 22345407 | Mgi Jnum | J:183258 |
| Mgi Id | MGI:5318141 | Doi | 10.1096/fj.11-202853 |
| Citation | Kang HW, et al. (2012) Thioesterase superfamily member 2/acyl-CoA thioesterase 13 (Them2/Acot13) regulates hepatic lipid and glucose metabolism. FASEB J 26(5):2209-21 |
| abstractText | Members of the acyl-CoA thioesterase (Acot) gene family catalyze the hydrolysis of fatty acyl-CoAs, but their biological functions remain unknown. Thioesterase superfamily member 2 (Them2; synonym Acot13) is a broadly expressed mitochondria-associated Acot. Them2 was previously identified as an interacting protein of phosphatidylcholine transfer protein (PC-TP). Pctp(-/-) mice exhibit altered fatty acid metabolism that is accompanied by reduced hepatic glucose production. To examine the role of Them2 in regulating hepatic lipid and glucose homeostasis, we generated Them2(-/-) mice. In livers of Them2(-/-) mice compared with Them2(+/+) controls, a 1.9-fold increase in the K(m) of mitochondrial thioesterase activity was accompanied by a 28% increase in fatty acyl-CoA concentration. A reciprocal 23% decrease in free fatty acid concentration was associated with reduced activation of peroxisome proliferator-activated receptor alpha. However, fatty acid oxidation rates were preserved in livers of Them2(-/-) mice, suggesting that Them2 functions to limit beta-oxidation. Hepatic glucose production was also decreased by 45% in the setting of reduced hepatocyte nuclear factor 4alpha (HNF4alpha) expression. When fed a high-fat diet, Them2(-/-) mice were resistant to increases in hepatic glucose production and steatosis. These findings reveal key roles for Them2 in the regulation of hepatic metabolism, which are potentially mediated by PC-TP-Them2 interactions.-Kang, H. W., Niepel, M. W., Han, S., Kawano, Y., Cohen, D. E. Thioesterase superfamily member 2/acyl-CoA thioesterase 13 (Them2/Acot13) regulates hepatic lipid and glucose metabolism. |
