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The Role of Mitochondrial Adaptation and Metabolic Flexibility in the Pathophysiology of Obesity and Insulin Resistance: an Updated Overview

  • Metabolism (M Dalamaga, Section Editor)
  • Published:
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Abstract

Purpose of Review

The term “metabolic flexibility” denotes the dynamic responses of the cellular oxidative machinery in order to adapt to changes in energy substrate availability. A progressive loss of this adaptive capacity has been implicated in the development of obesity-related comorbidities. Mitochondria are dynamic intracellular organelles which play a fundamental role in energy metabolism, and the mitochondrial adaptation to environmental challenges may be viewed as the functional component of metabolic flexibility. Herein, we attempt to comprehensively review the available evidence regarding the role of mitochondrial adaptation and metabolic flexibility in the pathogenesis of obesity and related morbidities, namely insulin resistance states and non-alcoholic fatty liver disease (NAFLD).

Recent Findings

Overall, there is a concrete body of evidence to support the presence of impaired mitochondrial adaptation as a principal component of systemic metabolic inflexibility in conditions related to obesity. There are still many unresolved questions regarding the relationship between the gradual loss of mitochondrial adaptability and the progression of obesity-related complications, such as causality issues, the timely appearance and reversibility of the described disturbances, and the generalizability of the findings to the mitochondrial content of every affected tissue or organ.

Summary

The evidence regarding the causality between the observed associations remains inconclusive, although most of the available data points towards a bidirectional, potentially mutually amplifying relationship. The spectrum of NAFLD is of particular interest, since functional and pathological changes in the course of its development closely mirror the progression of dysmetabolism, if not constituting a dynamic component of the latter.

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  1. First Department of Propaedeutic Internal Medicine, School of Medicine, Laiko General Hospital, National and Kapodistrian University of Athens, Athens, Greece

    Dimitrios Tsilingiris, Evangelia Tzeravini, Chrysi Koliaki & Alexander Kokkinos

  2. Department of Internal Medicine I and Clinical Chemistry, University of Heidelberg, Heidelberg, Germany

    Dimitrios Tsilingiris

  3. Department of Biological Chemistry, School of Medicine, National and Kapodistrian University of Athens, Mikras Asias 75, 11527, Athens, Greece

    Maria Dalamaga

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Tsilingiris, D., Tzeravini, E., Koliaki, C. et al. The Role of Mitochondrial Adaptation and Metabolic Flexibility in the Pathophysiology of Obesity and Insulin Resistance: an Updated Overview. Curr Obes Rep 10, 191–213 (2021). https://doi.org/10.1007/s13679-021-00434-0

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