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

Publication date: Available online 21 June 2018
Source:Cell Metabolism
Author(s): Elsa Pflimlin, Maximilian Bielohuby, Marcus Korn, Kristin Breitschopf, Matthias Löhn, Paulus Wohlfart, Anish Konkar, Michael Podeschwa, Felix Bärenz, Anja Pfenninger, Uwe Schwahn, Till Opatz, Marcel Reimann, Stefan Petry, Norbert Tennagels
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) -hydroxy-stearic 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 β cell line. Therefore, our data do not support the further development of PAHSAs or their derivatives for the control of insulin resistance and hyperglycemia.

Graphical abstract

Teaser

PAHSAs were previously recognized as a new class of mammalian lipids. Pflimlin et al. report a novel chemical synthesis for PAHSAs. In contrast to earlier reports, Pflimlin et al. did not observe beneficial effects on glucose metabolism after acute or repeated PAHSA treatment using cellular systems or mouse models of insulin resistance.


https://ift.tt/2M8Xh3C