Tissue-specific control of mitochondrial respiration in obesity-related insulin resistance and diabetes
Tissue-specific control of mitochondrial respiration in obesity-related insulin resistance and diabetes
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DOI：
10.1152/ajpendo.00159.2011
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发表时间：
2012-03-01
影响因子：
5.1
通讯作者：
Garcia-Roves, Pablo M.
中科院分区：
文献类型：
--
作者：
Holmstrom, Maria H.;Iglesias-Gutierrez, Eduardo;Garcia-Roves, Pablo M.
Holmstrom MH，Iglesias-Gutierrez E，Zierath JR，Garcia-Roves PM.肥胖相关胰岛素抵抗和糖尿病中线粒体呼吸的组织特异性控制。Am J Physiol Endocrinol Metab 302：E731-E739，2012.首次发表于2012年1月17日; doi：10.1152/ajpendo.00159.2011。线粒体呼吸能力在胰岛素抵抗和2型糖尿病发展中的组织特异性作用尚不清楚。我们测定了瘦（+/？）和肥胖糖尿病（db/db）小鼠。在瘦小鼠中，线粒体呼吸模式在组织之间不同。然后比较瘦小鼠和db/db小鼠之间的组织特异性线粒体谱。在肝脏中，db/db小鼠的线粒体呼吸能力和蛋白质表达（包括过氧化物酶体增殖物激活受体-γ共激活因子-1 α（PGC-1 α））降低，与线粒体分裂增加一致。在糖酵解肌肉中，db/db小鼠的线粒体呼吸以及线粒体标记物的蛋白质和mRNA表达增加，表明线粒体含量和脂肪酸氧化能力增加。在氧化肌肉中，db/db小鼠的线粒体复合物I功能和PGC-1 α和线粒体转录因子A（TFAM）蛋白水平降低，沿着与线粒体动力学相关的蛋白水平升高。总之，线粒体呼吸功能是在组织特异性机制的控制下，并没有统一改变肥胖。此外，糖酵解骨骼肌中的胰岛素抵抗可以通过独立于线粒体功能障碍的机制来维持。相反，db/db小鼠肝脏和氧化骨骼肌中的胰岛素抵抗与线粒体功能障碍一致。
Holmstrom MH, Iglesias-Gutierrez E, Zierath JR, Garcia-Roves PM. Tissue-specific control of mitochondrial respiration in obesity-related insulin resistance and diabetes. Am J Physiol Endocrinol Metab 302: E731-E739, 2012. First published January 17, 2012; doi:10.1152/ajpendo.00159.2011.-The tissue-specific role of mitochondrial respiratory capacity in the development of insulin resistance and type 2 diabetes is unclear. We determined mitochondrial function in glycolytic and oxidative skeletal muscle and liver from lean (+/?) and obese diabetic (db/db) mice. In lean mice, the mitochondrial respiration pattern differed between tissues. Tissue-specific mitochondrial profiles were then compared between lean and db/db mice. In liver, mitochondrial respiratory capacity and protein expression, including peroxisome proliferator-activated receptor-gamma coactivator-1 alpha (PGC-1 alpha), was decreased in db/db mice, consistent with increased mitochondrial fission. In glycolytic muscle, mitochondrial respiration, as well as protein and mRNA expression of mitochondrial markers, was increased in db/db mice, suggesting increased mitochondrial content and fatty acid oxidation capacity. In oxidative muscle, mitochondrial complex I function and PGC-1 alpha and mitochondrial transcription factor A (TFAM) protein levels were decreased in db/db mice, along with increased level of proteins related to mitochondrial dynamics. In conclusion, mitochondrial respiratory performance is under the control of tissue-specific mechanisms and is not uniformly altered in response to obesity. Furthermore, insulin resistance in glycolytic skeletal muscle can be maintained by a mechanism independent of mitochondrial dysfunction. Conversely, insulin resistance in liver and oxidative skeletal muscle from db/db mice is coincident with mitochondrial dysfunction.