Kolar Matthew J, Kamat Siddhesh S, Parsons William H, Homan Edwin A, Maher Tim, Peroni Odile D, Syed Ismail, Fjeld Karianne, Molven Anders, Kahn Barbara B, Cravatt Benjamin F, Saghatelian Alan
Peptide Biology Laboratories, Helmsley Center for Genomic Medicine, Salk Institute for Biological Studies , La Jolla, California 92037, United States.
Department of Chemical Physiology, Skaggs Institute of Chemical Biology, The Scripps Research Institute , La Jolla, California 92037, United States.
Biochemistry. 2016 Aug 23;55(33):4636-41. doi: 10.1021/acs.biochem.6b00565. Epub 2016 Aug 10.
A recently discovered class of endogenous mammalian lipids, branched fatty acid esters of hydroxy fatty acids (FAHFAs), possesses anti-diabetic and anti-inflammatory activities. Here, we identified and validated carboxyl ester lipase (CEL), a pancreatic enzyme hydrolyzing cholesteryl esters and other dietary lipids, as a FAHFA hydrolase. Variants of CEL have been linked to maturity-onset diabetes of the young, type 8 (MODY8), and to chronic pancreatitis. We tested the FAHFA hydrolysis activity of the CEL MODY8 variant and found a modest increase in activity as compared with that of the normal enzyme. Together, the data suggest that CEL might break down dietary FAHFAs.
最近发现的一类内源性哺乳动物脂质——羟基脂肪酸的支链脂肪酸酯（FAHFAs）具有抗糖尿病和抗炎活性。在此，我们鉴定并验证了羧基酯酶（CEL），一种水解胆固醇酯和其他膳食脂质的胰腺酶，作为一种FAHFA水解酶。CEL的变体与青年发病的成年型糖尿病8型（MODY8）以及慢性胰腺炎有关。我们测试了CEL MODY8变体的FAHFA水解活性，发现与正常酶相比，其活性有适度增加。综合这些数据表明，CEL可能分解膳食中的FAHFAs。
