比较棕榈酸盐、胰岛素及棕榈酸盐-胰岛素联合治疗对肌管代谢和胰岛素抵抗的影响

IF 1.8 4区 医学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY
Lipids Pub Date : 2021-08-12 DOI:10.1002/lipd.12315
Madison E. Rivera, Roger A. Vaughan
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引用次数: 1

摘要

先前的研究表明,各种代谢应激源,如饱和脂肪酸(SFA)和过量的胰岛素,会促进代谢有意义的细胞类型(如骨骼肌)的胰岛素抵抗。此外,这些应激源与线粒体代谢抑制有关,这也是糖尿病患者骨骼肌的共同特征。本研究探讨了过量脂质和过量胰岛素对肌管代谢及相关代谢基因和蛋白表达的单独和联合影响。C2C12肌管分别用500 μM棕榈酸酯(PAM)、100 nM胰岛素(IR)或两者(PAM-IR)处理。采用qRT-PCR和western blot分别检测代谢基因和蛋白的表达。用耗氧量测量线粒体代谢。通过细胞外酸化率测量糖酵解代谢和胰岛素介导的葡萄糖摄取。采用尼罗红和NAO染色分别测定细胞脂质和线粒体含量。IR和PAM-IR处理导致p-Akt表达降低。IR治疗降低了胰岛素介导的葡萄糖代谢,而PAM和PAM-IR治疗增加了线粒体代谢,同时降低了线粒体代谢。三种处理均显示线粒体代谢受到抑制。PAM和PAM- ir也显示糖酵解代谢增加。虽然PAM和PAM- ir显著增加了脂肪含量,但炎症蛋白和脂肪生成蛋白的表达没有改变。最后,PAM-IR降低BCAT2蛋白的表达,BCAT2蛋白是BCAA代谢的调节因子。两种应激源都能独立降低胰岛素信号、线粒体功能和细胞代谢,然而,只有PAM-IR共同处理才能显著降低代谢调节因子的表达,这在单独的应激源中是看不到的,这表明应激源对代谢编程有累加效应。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Comparing the effects of palmitate, insulin, and palmitate-insulin co-treatment on myotube metabolism and insulin resistance
Previous studies have shown various metabolic stressors such as saturated fatty acids (SFA) and excess insulin promote insulin resistance in metabolically meaningful cell types (such as skeletal muscle). Additionally, these stressors have been linked with suppressed mitochondrial metabolism, which is also a common characteristic of skeletal muscle of diabetics. This study characterized the individual and combined effects of excess lipid and excess insulin on myotube metabolism and related metabolic gene and protein expression. C2C12 myotubes were treated with either 500 μM palmitate (PAM), 100 nM insulin (IR), or both (PAM-IR). qRT-PCR and western blot were used to measure metabolic gene and protein expression, respectively. Oxygen consumption was used to measure mitochondrial metabolism. Glycolytic metabolism and insulin-mediated glucose uptake were measured via extracellular acidification rate. Cellular lipid and mitochondrial content were measured using Nile Red and NAO staining, respectively. IR and PAM-IR treatments led to reductions in p-Akt expression. IR treatment reduced insulin mediated glucose metabolism while PAM and PAM-IR treatment showed increases with concurrent reductions in mitochondrial metabolism. All three treatments showed suppression in mitochondrial metabolism. PAM and PAM-IR also showed increases in glycolytic metabolism. While PAM and PAM-IR significantly increased lipid content, expression of inflammatory and lipogenic proteins were unaltered. Lastly, PAM-IR reduced BCAT2 protein expression, a regulator of BCAA metabolism. Both stressors independently reduced insulin signaling, mitochondrial function, and cell metabolism, however, only PAM-IR co-treatment significantly reduced the expression of regulators of metabolism not seen with individual stressors, suggesting an additive effect of stressors on metabolic programming.
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来源期刊
Lipids
Lipids 生物-生化与分子生物学
CiteScore
4.20
自引率
5.30%
发文量
33
审稿时长
4-8 weeks
期刊介绍: Lipids is a journal of the American Oil Chemists'' Society (AOCS) that focuses on publishing high-quality peer-reviewed papers and invited reviews in the general area of lipid research, including chemistry, biochemistry, clinical nutrition, and metabolism. In addition, Lipids publishes papers establishing novel methods for addressing research questions in the field of lipid research.
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