Bhansali Shipra, Bhansali Anil, Dhawan Veena
Department of Experimental Medicine and Biotechnology, Postgraduate Institute of Medical Education and Research (PGIMER), Research Block-B, Chandigarh, 160012 India.
Department of Endocrinology, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India.
Diabetol Metab Syndr. 2017 Dec 12;9:99. doi: 10.1186/s13098-017-0298-x. eCollection 2017.
Obesity-mediated oxidative stress results in mitochondrial dysfunction, which has been implicated in the pathogenesis of metabolic syndrome and T2DM. Recently, mitophagy, a cell-reparative process has emerged as a key facet in maintaining the mitochondrial health, which may contribute to contain the metabolic abnormalities in obese individuals. However, the status of mitophagy in metabolically healthy obese (MHO) and metabolically abnormal diabetic obese (MADO) subjects remains to be elucidated. Hence, the present study aims to unravel the alterations in mitochondrial oxidative stress (MOS) and mitophagy in these subjects.
60 subjects including MHNO (metabolically healthy non-obese), MHO and MADO were enrolled as per the Asian criteria for obesity (n = 20 each). Biochemical parameters, MOS indices, transcriptional and translational expression of mitophagy markers (, , , , -, and -), and transmission electron microscopic (TEM) studies were performed in peripheral blood mononuclear cells.
The MHO subjects displayed a favorable metabolic profile, despite accompanied by an increased adiposity as compared to the MHNO group; while MADO group exhibited several metabolic abnormalities, inspite of similar body composition as MHO subjects. A progressive rise in the MOS was observed in MHO and MADO subjects as compared to the MHNO group, and it showed a positive and significant correlation with the body composition in these groups. Further, mitophagy remained unaltered in the MHO group, while it was significantly downregulated in the MADO group. In addition, TEM studies revealed a significant increase in the percentage of damaged mitochondria in MADO patients as compared to other groups, while MHO and MHNO groups did not show any significant alterations for the same.
A favorable metabolic profile and moderate levels of MOS in the MHO group may play a crucial role in the sustenance of mitophagy, which may further limit the aggravation of MOS, inflammation, and emergence of metabolic aberrations in contrast to MADO subjects, who exhibited multiple metabolic abnormalities and attenuated mitophagy. Therefore, these MHO subjects are likely to be at a lower risk of developing metabolic syndrome and T2DM.
肥胖介导的氧化应激会导致线粒体功能障碍，这与代谢综合征和2型糖尿病的发病机制有关。最近，线粒体自噬作为一种细胞修复过程，已成为维持线粒体健康的关键因素，这可能有助于控制肥胖个体的代谢异常。然而，代谢健康的肥胖（MHO）和代谢异常的糖尿病肥胖（MADO）受试者中线粒体自噬的状态仍有待阐明。因此，本研究旨在揭示这些受试者线粒体氧化应激（MOS）和线粒体自噬的变化。
根据亚洲肥胖标准，纳入60名受试者，包括代谢健康的非肥胖者（MHNO）、MHO和MADO（每组n = 20）。对外周血单个核细胞进行生化参数、MOS指标、线粒体自噬标志物（ 、 、 、 、 -和 -）的转录和翻译表达以及透射电子显微镜（TEM）研究。
与MHNO组相比，MHO受试者尽管肥胖程度增加，但仍表现出良好的代谢特征；而MADO组尽管身体组成与MHO受试者相似，但表现出多种代谢异常。与MHNO组相比，MHO和MADO受试者的MOS逐渐升高，并且在这些组中与身体组成呈正相关且具有显著相关性。此外，MHO组中线粒体自噬保持不变，而MADO组中线粒体自噬显著下调。此外，TEM研究显示，与其他组相比，MADO患者中受损线粒体的百分比显著增加，而MHO和MHNO组未显示出任何显著变化。
MHO组良好的代谢特征和适度的MOS水平可能在维持线粒体自噬中起关键作用，这可能进一步限制MOS的加重、炎症以及代谢异常的出现，而MADO受试者表现出多种代谢异常且线粒体自噬减弱。因此，这些MHO受试者发生代谢综合征和2型糖尿病的风险可能较低。
