title: Lipid mixtures containing a very high proportion of saturated fatty acids only modestly impair insulin signaling in cultured muscle cells.
abstract: In vitro examinations of the effect of saturated fatty acids on skeletal muscle insulin action often use only one or two different fatty acid species, which does not resemble the human plasma fatty acid profile. We compared graded concentrations (0.1-0.8 mM) of 3 different lipid mixtures: 1) a physiologic fatty acid mixture (NORM; 40% saturated fatty acids), 2) a physiologic mixture high in saturated fatty acids (HSFA; 60% saturated fatty acids), and 3) 100% palmitate (PALM) on insulin signaling and fatty acid partitioning into triacylglycerol (TAG) and diacylglycerol (DAG) in cultured muscle cells. As expected, PALM readily impaired insulin-stimulated pAktThr308/Akt and markedly increased intracellular DAG content. In contrast, the fatty acid mixtures only modestly impaired insulin-stimulated pAktThr308M/Akt, and we found no differences between NORM and HSFA. Importantly, NORM and HSFA did not increase DAG content, but instead dose-dependently increased TAG accumulation. Therefore, the robust impairment in insulin signaling found with palmitate exposure was attenuated with physiologic mixtures of fatty acids, even with a very high proportion of saturated fatty acids. This may be explained in part by selective partitioning of fatty acids into neutral lipid (i.e., TAG) when muscle cells were exposed to physiologic lipid mixtures.
authors: Substrate Metabolism Laboratory, School of Kinesiology, University of Michigan, Ann Arbor, Michigan, United States of America.
authors: Sean A
authors: SA
authors: Newsom
authors: Substrate Metabolism Laboratory, School of Kinesiology, University of Michigan, Ann Arbor, Michigan, United States of America.
authors: Allison C
authors: AC
authors: Everett
authors: Substrate Metabolism Laboratory, School of Kinesiology, University of Michigan, Ann Arbor, Michigan, United States of America.
authors: Sanghee
authors: S
authors: Park
authors: Substrate Metabolism Laboratory, School of Kinesiology, University of Michigan, Ann Arbor, Michigan, United States of America.
authors: Douglas W
authors: DW
authors: Van Pelt
authors: Substrate Metabolism Laboratory, School of Kinesiology, University of Michigan, Ann Arbor, Michigan, United States of America.
authors: Alexander
authors: A
authors: Hinko
authors: Substrate Metabolism Laboratory, School of Kinesiology, University of Michigan, Ann Arbor, Michigan, United States of America.
authors: Jeffrey F
authors: JF
authors: Horowitz
mesh_terms: D000818:Animals; D002460:Cell Line; D002478:Cells, Cultured; D005227:Fatty Acids / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D050356:Lipid Metabolism; D051379:Mice; D018485:Muscle Fibers, Skeletal / Q000187:drug effects / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D005227:Fatty Acids; D007328:Insulin