Acute and Repeated Treatment with 5-PAHSA or 9-PAHSA Isomers Does Not Improve Glucose Control in Mice

作者：Pflimlin Elsa; Bielohuby Maximilian^*; Korn Marcus; Breitschopf Kristin; Loehn Matthias; Wohlfart Paulus; Konkar Anish; Podeschwa Michael; Baerenz Felix; Pfenninger Anja; Schwahn Uwe; Opatz Till; Reimann Marcel; Petry Stefan; Tennagels Norbert^*

来源：Cell Metabolism, 2018, 28(2): 217-+.

DOI：10.1016/j.cmet.2018.05.028

Fatty acid esters of hydroxylated fatty acids (FAHFAs) were discovered as a novel class of endogenous mammalian lipids whose profound effects on metabolism have been shown. In the current study, in vitro and in vivo the metabolic effects of two of these FAHFAs, namely palmitic acid-5- (or -9) -hydroxystearic acid (5- or 9-PAHSA, respectively) were profiled. In DIO mice fed with differentially composed low- or high-fat diets, acute and subchronic treatment with 5-PAHSA and 9-PAHSA alone, or in combination, did not significantly improve the deranged metabolic status. Neither racemic 5- or 9-PAHSA, nor the enantiomers were able to: (1) increase basal or insulin-stimulated glucose uptake in vitro, (2) stimulate GLP-1 release from GLUTag cells, or (3) induce GSIS in rat, mouse, or human islets or in a human pancreatic beta cell line. Therefore, our data do not support the further development of PAHSAs or their derivatives for the control of insulin resistance and hyperglycemia.

• 出版日期2018-8-7