Flattening of circadian glucocorticoid oscillations drives acute hyperinsulinemia and adipocyte hypertrophy. Academic Article uri icon

Overview

abstract

  • Disruption of circadian glucocorticoid oscillations in Cushing's disease and chronic stress results in obesity and adipocyte hypertrophy, which is believed to be a main source of the harmful effects of obesity. Here, we recapitulate stress due to jet lag or work-life imbalances by flattening glucocorticoid oscillations in mice. Within 3 days, mice achieve a metabolic state with persistently high insulin, but surprisingly low glucose and fatty acids in the bloodstream, that precedes a more than 2-fold increase in brown and white adipose tissue mass within 3 weeks. Transcriptomic and Cd36-knockout mouse analyses show that hyperinsulinemia-mediated de novo fatty acid synthesis and Cd36-mediated fatty acid uptake drive fat mass increases. Intriguingly, this mechanism by which glucocorticoid flattening causes acute hyperinsulinemia and adipocyte hypertrophy is unexpectedly beneficial in preventing high levels of circulating fatty acids and glucose for weeks, thus serving as a protective response to preserve metabolic health during chronic stress.

publication date

  • June 28, 2022

Research

keywords

  • Glucocorticoids
  • Hyperinsulinism

Identity

PubMed Central ID

  • PMC9391061

Scopus Document Identifier

  • 85133145285

Digital Object Identifier (DOI)

  • 10.1210/jcem-33-1-14

PubMed ID

  • 35767959

Additional Document Info

volume

  • 39

issue

  • 13