Favourable metabolic profile sustains mitophagy and prevents metabolic abnormalities in metabolically healthy obese individuals

Shipra Bhansali,Veena Dhawan,Anil Bhansali

doi:10.1186/s13098-017-0298-x

Abstract

BackgroundObesity-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.Methods60 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 (PINK1, PARKIN, MFN2, NIX, LC3-II, and LAMP-2), and transmission electron microscopic (TEM) studies were performed in peripheral blood mononuclear cells.ResultsThe 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.ConclusionA 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.

Highlights

Obesity-mediated oxidative stress results in mitochondrial dysfunction, which has been implicated in the pathogenesis of metabolic syndrome and type 2 diabetes mellitus (T2DM)
metabolically healthy obese (MHO) subjects are characterized by the absence of several metabolic abnormalities such as insulin resistance, dyslipidemia, glucose intolerance, hypertension, inspite of increased adiposity, but have a favorable inflammatory profile as compared to the metabolically abnormal diabetic obese (MADO) individuals, who are usually accompanied by severe metabolic abnormalities
The anthropometric measurements including weight, BMI, waist circumference (WC), and body fat % were significantly higher in MHO and MADO subjects as compared to the Metabolically healthy non-obese (MHNO) group, while they were comparable between MHO and MADO subjects (p < 0.05)

Summary

Introduction

Obesity-mediated oxidative stress results in mitochondrial dysfunction, which has been implicated in the pathogenesis of metabolic syndrome and T2DM. The status of mitophagy in metabolically healthy obese (MHO) and metabolically abnormal diabetic obese (MADO) subjects remains to be elucidated. Obesity is associated with numerous metabolic alterations such as insulin resistance, glucose intolerance, and dyslipidemia. The constellation of these risk factors constitute the metabolic syndrome that predisposes the individuals to the risk of developing type 2 diabetes mellitus (T2DM) and cardiovascular diseases [1, 2]. MHO subjects are characterized by the absence of several metabolic abnormalities such as insulin resistance, dyslipidemia, glucose intolerance, hypertension, inspite of increased adiposity, but have a favorable inflammatory profile as compared to the metabolically abnormal diabetic obese (MADO) individuals, who are usually accompanied by severe metabolic abnormalities. The underlying mechanisms contributing towards the relative protection against obesity-induced metabolic complications remains largely unknown

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