2. Academic Validation
  3. Branched Fatty Acid Esters of Hydroxy Fatty Acids Are Preferred Substrates of the MODY8 Protein Carboxyl Ester Lipase

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

  • Biochemistry. 2016 Aug 23;55(33):4636-41. doi: 10.1021/acs.biochem.6b00565.
Matthew J Kolar 1,  Siddhesh S Kamat 2,  William H Parsons 2,  Edwin A Homan 3,  Tim Maher 3,  Odile D Peroni 4,  Ismail Syed 4,  Karianne Fjeld 5 6,  Anders Molven 7 8,  Barbara B Kahn 4,  Benjamin F Cravatt 2,  Alan Saghatelian 1
Affiliations

Affiliations

  • 1 Peptide Biology Laboratories, Helmsley Center for Genomic Medicine, Salk Institute for Biological Studies , La Jolla, California 92037, United States.
  • 2 Department of Chemical Physiology, Skaggs Institute of Chemical Biology, The Scripps Research Institute , La Jolla, California 92037, United States.
  • 3 Department of Chemistry and Chemical Biology, Harvard University , Cambridge, Massachusetts 02138, United States.
  • 4 Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School , Boston, Massachusetts 02215, United States.
  • 5 KG Jebsen Center for Diabetes Research, Department of Clinical Science, University of Bergen , N-5021 Bergen, Norway.
  • 6 Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital , N-5021 Bergen, Norway.
  • 7 Gade Laboratory for Pathology, Department of Clinical Medicine, University of Bergen , N-5021 Bergen, Norway.
  • 8 Department of Pathology, Haukeland University Hospital , N-5021 Bergen, Norway.
PMID: 27509211 DOI: 10.1021/acs.biochem.6b00565
Abstract

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.

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