title: Branched Fatty Acid Esters of Hydroxy Fatty Acids Are Preferred Substrates of the MODY8 Protein Carboxyl Ester Lipase.
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.
authors: Peptide Biology Laboratories, Helmsley Center for Genomic Medicine, Salk Institute for Biological Studies , La Jolla, California 92037, United States.
authors: Matthew J
authors: MJ
authors: Kolar
authors: Department of Chemical Physiology, Skaggs Institute of Chemical Biology, The Scripps Research Institute , La Jolla, California 92037, United States.
authors: Siddhesh S
authors: SS
authors: Kamat
authors: Department of Chemical Physiology, Skaggs Institute of Chemical Biology, The Scripps Research Institute , La Jolla, California 92037, United States.
authors: William H
authors: WH
authors: Parsons
authors: Department of Chemistry and Chemical Biology, Harvard University , Cambridge, Massachusetts 02138, United States.
authors: Edwin A
authors: EA
authors: Homan
authors: Department of Chemistry and Chemical Biology, Harvard University , Cambridge, Massachusetts 02138, United States.
authors: Tim
authors: T
authors: Maher
authors: Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School , Boston, Massachusetts 02215, United States.
authors: Odile D
authors: OD
authors: Peroni
authors: Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School , Boston, Massachusetts 02215, United States.
authors: Ismail
authors: I
authors: Syed
authors: KG Jebsen Center for Diabetes Research, Department of Clinical Science, University of Bergen , N-5021 Bergen, Norway.|Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital , N-5021 Bergen, Norway.
authors: Karianne
authors: K
authors: Fjeld
authors: Gade Laboratory for Pathology, Department of Clinical Medicine, University of Bergen , N-5021 Bergen, Norway.|Department of Pathology, Haukeland University Hospital , N-5021 Bergen, Norway.
authors: Anders
authors: A
authors: Molven
authors: Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School , Boston, Massachusetts 02215, United States.
authors: Barbara B
authors: BB
authors: Kahn
authors: Department of Chemical Physiology, Skaggs Institute of Chemical Biology, The Scripps Research Institute , La Jolla, California 92037, United States.
authors: Benjamin F
authors: BF
authors: Cravatt
authors: Peptide Biology Laboratories, Helmsley Center for Genomic Medicine, Salk Institute for Biological Studies , La Jolla, California 92037, United States.
authors: Alan
authors: A
authors: Saghatelian
mesh_terms: D043182:Carboxylesterase / Q000378:metabolism*; D004952:Esters; D005227:Fatty Acids / Q000737:chemistry*; D013379:Substrate Specificity
chemical_list: D004952:Esters; D005227:Fatty Acids; D043182:Carboxylesterase