Branched Fatty Acid Esters of Hydroxy Fatty Acids Are Preferred Substrates of the MODY8 Protein Carboxyl Ester Lipase

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• 作者：Matthew J. Kolar ; Siddhesh S. Kamat ; William H. Parsons ; Edwin A. Homan ; Tim Maher ; Odile D. Peroni ; Ismail Syed ; Karianne Fjeld ; Anders Molven ; Barbara B. Kahn ; Benjamin F. Cravatt ; Alan Saghatelian
• 刊名：Biochemistry
• 出版年：2016
• 出版时间：August 23, 2016
• 年：2016
• 卷：55
• 期：33
• 页码：4636-4641
• 全文大小：346K
• 年卷期：0
• ISSN：1520-4995

文摘

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.