Mitochondrial lipid oxidation is impaired in cultured myotubes from obese humans.
Mitochondrial lipid oxidation is impaired in cultured myotubes from obese humans.
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DOI：
10.1038/ijo.2011.201
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发表时间：
2012-08
影响因子：
4.9
通讯作者：
Houmard, J. A.
中科院分区：
文献类型：
--
作者：
Boyle, K. E.;Zheng, D.;Anderson, E. J.;Neufer, P. D.;Houmard, J. A.
肥胖人的骨骼肌的特征在于不能适当地响应底物可用性的改变。本研究的目的是确定这种肥胖的代谢能力是否保留在培养的人骨骼肌细胞（HSkMC）的线粒体中，并确定相关的潜在机制。线粒体呼吸测定透化肌管培养从瘦和肥胖的个人之前和之后的24小时脂质孵育。在脂质底物（棕榈酰肉毒碱）存在下的线粒体呼吸（状态3）在来自瘦而非肥胖受试者的HSkMC中的脂质孵育后增加了几乎2倍，指示肥胖的代谢不稳定性。24 h脂质孵育使瘦型受试者HSkMC中的线粒体DNA（mtDNA）拷贝数增加了+16%（P<0.05）;相反，肥胖个体培养的肌管中的mtDNA拷贝数减少了（-13%，P=0.06）。当呼吸数据被标准化为线粒体DNA拷贝数和其他线粒体含量指数（COX-IV蛋白含量和CS活性）时，在瘦的受试者中，脂质孵育的显著治疗效果持续存在，表明线粒体功能的伴随改变;在肥胖个体的HSkMC中没有明显的类似调整。这些数据表明，肥胖个体的骨骼肌固有地缺乏对脂质暴露的代谢灵活性，其包括在脂质底物存在下不能增加线粒体呼吸，并且可能不能诱导线粒体增殖。
The skeletal muscle of obese humans is characterized by an inability to appropriately respond to alterations in substrate availability. The purpose of the current study was to determine if this metabolic inflexibility with obesity is retained in mitochondria of human skeletal muscle cells raised in culture (HSkMC) and to identify potential mechanisms involved. Mitochondrial respiration was measured in permeabilized myotubes cultured from lean and obese individuals before and after a 24 h lipid incubation. Mitochondrial respiration (State 3) in the presence of lipid substrate (palmitoyl carnitine) increased by almost 2-fold after lipid incubation in HSkMC from lean, but not obese subjects, indicative of metabolic inflexibility with obesity. The 24 h lipid incubation increased mitochondrial DNA (mtDNA) copy number in HSkMC from lean subjects by +16% (P<0.05); conversely, mtDNA copy number decreased in myotubes cultured from obese individuals (−13%, P=0.06). When respiration data were normalized to mtDNA copy number and other indices of mitochondrial content (COX-IV protein content and CS activity), the significant treatment effects of lipid incubationpersisted in the lean subjects, suggesting concomitant alterations in mitochondrial function; no similar adjustment was evident in HSkMC from obese individuals. These data indicate that the skeletal muscle of obese individuals inherently lacks metabolic flexibility in response to lipid exposure, which consists of an inability to increase mitochondrial respiration in the presence of lipid substrate and perhaps by an inability to induce mitochondrial proliferation.
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影响因子：
15.9
作者：
Anderson, Ethan J.;Lustig, Mary E.;Neufer, P. Darrell
通讯作者：
Neufer, P. Darrell
影响因子：
7.7
作者：
Kelley, DE;Mandarino, LJ
通讯作者：
Mandarino, LJ
影响因子：
29
作者：
Hulver, MW;Berggren, JR;Muoio, DM
通讯作者：
Muoio, DM
影响因子：
7.7
作者：
Consitt LA;Bell JA;Koves TR;Muoio DM;Hulver MW;Haynie KR;Dohm GL;Houmard JA
通讯作者：
Houmard JA
DOI：
10.1152/ajpendo.2000.279.5.e1039
发表时间：
2000-11-01
影响因子：
5.1
作者：
Kim, JY;Hickner, RC;Houmard, JA
通讯作者：
Houmard, JA