Title | Flattening of circadian glucocorticoid oscillations drives acute hyperinsulinemia and adipocyte hypertrophy. |
Publication Type | Journal Article |
Year of Publication | 2022 |
Authors | Tholen S, Patel R, Agas A, Kovary KM, Rabiee A, Nicholls HT, Bielczyk-Maczyńska E, Yang W, Kraemer FB, Teruel MN |
Journal | Cell Rep |
Volume | 39 |
Issue | 13 |
Pagination | 111018 |
Date Published | 2022 Jun 28 |
ISSN | 2211-1247 |
Keywords | Adipocytes, 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. |
DOI | 10.1016/j.celrep.2022.111018 |
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Alternate Journal | Cell Rep |
PubMed ID | 35767959 |
PubMed Central ID | PMC9391061 |
Grant List | I01 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 |