骨骼肌和脂肪组织中线粒体呼吸和数量对运动的反应在患有前驱糖尿病的人中
The response of mitochondrial respiration and quantity in skeletal muscle and adipose tissue to exercise in humans with prediabetes.
Keywords:type 2 diabetes; obesity; mitochondria; muscle; adipose tissue; fat; exercise; prediabetes
关键词: 2型糖尿病;肥胖; 线粒体;肌肉; 脂肪组织;脂肪; 锻炼;糖尿病前期
组织:骨骼肌,脂肪
作者:Szczerbinski L、Taylor MA、Puchta U、Konopka P、Paszko A、Citko A、Szczerbinski K、Goscik J、Gorska M、Larsen S、Kretowski A
出版期刊:《 Cells 》(2021/4/23)
Abstract:
Background: Mitochondrial dysfunction has been implicated in the pathogenesis of type 2 diabetes, but its contribution to the early stages of dysglycemia remains poorly understood. By collecting a high-resolution stage-based spectrum of dysglycemia, our study fills this gap by evaluating derangement in both the function and quantity of mitochondria. We sampled mitochondria in skeletal muscle and subcutaneous adipose tissues of subjects with progressive advancement of dysglycemia under a three-month exercise intervention. Methods: We measured clinical metabolic parameters and gathered skeletal muscle and adipose tissue biopsies before and after the three-month exercise intervention. We then assayed the number of mitochondria via citrate synthase (CS) activity and functional parameters with high-resolution respirometry. Results: In muscle, there were no differences in mitochondrial quantity or function at baseline between normoglycemics and prediabetics. However, the intervention caused improvement in CS activity, implying an increase in mitochondrial quantity. By contrast in adipose tissue, baseline differences in CS activity were present, with the lowest CS activity coincident with impaired fasting glucose and impaired glucose tolerance (IFG + IGT). Finally, CS activity, but few of the functional metrics, improved under the intervention. Conclusions: We show that in prediabetes, no differences in the function or amount of mitochondria (measured by CS activity) in skeletal muscle are apparent, but in adipose tissue of subjects with IFG + IGT, a significantly reduced activity of CS was observed. Finally, metabolic improvements under the exercise correlate to improvements in the amount, rather than function, of mitochondria in both tissues.
文章摘要:
线粒体功能障碍与 2 型糖尿病的发病机制有关,但其对血糖异常早期阶段的贡献仍知之甚少。通过收集高分辨率的基于阶段的血糖异常谱,我们的研究通过评估线粒体功能和数量的紊乱来填补这一空白。我们在三个月的运动干预下对血糖异常进展的受试者的骨骼肌和皮下脂肪组织中的线粒体进行了采样。方法:我们测量了临床代谢参数,并在三个月的运动干预前后收集了骨骼肌和脂肪组织活检。然后,我们通过柠檬酸合酶 (CS) 活性和高分辨率呼吸功能参数测定线粒体的数量。结果:在肌肉中,血糖正常者和糖尿病前期患者在基线时的线粒体数量或功能没有差异。然而,干预导致 CS 活性的改善,这意味着线粒体数量的增加。相比之下,在脂肪组织中,CS 活性存在基线差异,最低 CS 活性与空腹血糖受损和糖耐量受损 (IFG + IGT) 一致。最后,CS 活动(但很少有功能指标)在干预下有所改善。结论:我们表明,在糖尿病前期,骨骼肌中线粒体的功能或数量(通过 CS 活性测量)没有明显差异,但在 IFG + IGT 受试者的脂肪组织中,观察到 CS 活性显着降低。最后,运动下的代谢改善与两种组织中线粒体数量而非功能的改善相关。
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