Flattening of circadian glucocorticoid oscillations drives acute hyperinsulinemia and adipocyte hypertrophy.

TitleFlattening of circadian glucocorticoid oscillations drives acute hyperinsulinemia and adipocyte hypertrophy.
Publication TypeJournal Article
Year of Publication2022
AuthorsTholen S, Patel R, Agas A, Kovary KM, Rabiee A, Nicholls HT, Bielczyk-Maczyńska E, Yang W, Kraemer FB, Teruel MN
JournalCell Rep
Volume39
Issue13
Pagination111018
Date Published2022 Jun 28
ISSN2211-1247
KeywordsAdipocytes, Animals, Fatty Acids, Glucocorticoids, Glucose, Hyperinsulinism, Hypertrophy, Mice, Obesity
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.

DOI10.1016/j.celrep.2022.111018
Custom 1

https://www.ncbi.nlm.nih.gov/pubmed/35767959?dopt=Abstract

Alternate JournalCell Rep
PubMed ID35767959
PubMed Central IDPMC9391061
Grant ListI01 BX000398 / BX / BLRD VA / United States
R01 DK103046 / DK / NIDDK NIH HHS / United States
R56 DK131432 / DK / NIDDK NIH HHS / United States
P50 GM107615 / GM / NIGMS NIH HHS / United States
R01 DK101743 / DK / NIDDK NIH HHS / United States
R01 DK106241 / DK / NIDDK NIH HHS / United States

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