6533b82ffe1ef96bd129598c

RESEARCH PRODUCT

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

Elsa PflimlinAnish KonkarNorbert TennagelsStefan PetryKristin BreitschopfPaulus WohlfartMarcus KornMaximilian BielohubyAnja PfenningerUwe SchwahnFelix BärenzMatthias LöhnMichael PodeschwaTill OpatzMarcel Reimann

subject

0301 basic medicinechemistry.chemical_classificationgeographymedicine.medical_specialtygeography.geographical_feature_categoryPhysiologyGlucose uptakeFatty acid030209 endocrinology & metabolismEndogenyCell BiologyMetabolismIsletmedicine.disease03 medical and health sciencesBasal (phylogenetics)030104 developmental biology0302 clinical medicineInsulin resistanceEndocrinologychemistryCell cultureInternal medicinemedicineMolecular Biology

description

Summary 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.

https://doi.org/10.1016/j.cmet.2018.05.028