Newsom Sean A, Everett Allison C, Park Sanghee, Van Pelt Douglas W, Hinko Alexander, Horowitz Jeffrey F
Substrate Metabolism Laboratory, School of Kinesiology, University of Michigan, Ann Arbor, Michigan, United States of America.
PLoS One. 2015 Mar 20;10(3):e0120871. doi: 10.1371/journal.pone.0120871. eCollection 2015.
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.
体外研究饱和脂肪酸对骨骼肌胰岛素作用的影响时，通常仅使用一两种不同的脂肪酸种类，这与人类血浆脂肪酸谱并不相似。我们比较了3种不同脂质混合物的梯度浓度（0.1 - 0.8 mM）：1）生理脂肪酸混合物（NORM；40%饱和脂肪酸），2）高饱和脂肪酸的生理混合物（HSFA；60%饱和脂肪酸），以及3）100%棕榈酸（PALM）对培养的肌肉细胞中胰岛素信号传导以及脂肪酸向三酰甘油（TAG）和二酰甘油（DAG）的分配的影响。正如预期的那样，PALM很容易损害胰岛素刺激的pAktThr308/Akt，并显著增加细胞内DAG含量。相比之下，脂肪酸混合物仅适度损害胰岛素刺激的pAktThr308M/Akt，并且我们发现NORM和HSFA之间没有差异。重要的是，NORM和HSFA并未增加DAG含量，而是剂量依赖性地增加TAG积累。因此，即使饱和脂肪酸比例非常高，脂肪酸的生理混合物也会减弱棕榈酸暴露时发现的胰岛素信号的强烈损害。这可能部分是由于当肌肉细胞暴露于生理脂质混合物时，脂肪酸选择性地分配到中性脂质（即TAG）中。
