Pathophysiological role of metabolic flexibility on metabolic health

Obes Rev. 2021 Feb;22(2):e13131. doi: 10.1111/obr.13131. Epub 2020 Aug 19.


Glucose, fatty acids, and amino acids among others are oxidized to generate adenosine triphosphate (ATP). These fuels are supplied from the environment (through food intake) and internal depots (through lipolysis, glycogenolysis, and proteolysis) at different rates throughout the day. Complex adaptive systems permit to accommodate fuel oxidation according to fuel availability. This capacity of a cell, tissue, or organism to adapt fuel oxidation to fuel availability is defined as metabolic flexibility (MetF). There are conditions, such as insulin resistance, diabetes, and obesity, in which MetF seems to be impaired. The observation that those conditions are accompanied by mitochondrial dysfunction has set the basis to propose a link between mitochondrial dysfunction, metabolic inflexibility, and metabolic health. We here highlight the evidence about the notion that MetF influences metabolic health.

Keywords: Insulin resistance; Insulin sensitivity; Lipotoxicity; Obesity.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Amino Acids / metabolism
  • Energy Metabolism*
  • Fatty Acids / metabolism
  • Glucose / metabolism
  • Glycogenolysis
  • Humans
  • Insulin Resistance
  • Lipolysis
  • Mitochondria / pathology
  • Obesity
  • Oxidation-Reduction
  • Proteolysis


  • Amino Acids
  • Fatty Acids
  • Glucose