bims-ciryme 2022-07-03 papers

Sci Adv. 2022 Jul;8(26): eabo2896

The central clock suffices to drive the majority of circulatory metabolic rhythms.

Paul Petrus, Jacob G Smith, Kevin B Koronowski, Siwei Chen, Tomoki Sato, Carolina M Greco, Thomas Mortimer, Patrick-Simon Welz, Valentina M Zinna, Kohei Shimaji, Marlene Cervantes, Daniela Punzo, Pierre Baldi, Pura Muñoz-Cánoves, Paolo Sassone-Corsi, Salvador Aznar Benitah.

Life on Earth anticipates recurring 24-hour environmental cycles via genetically encoded molecular clocks active in all mammalian organs. Communication between these clocks controls circadian homeostasis. Intertissue communication is mediated, in part, by temporal coordination of metabolism. Here, we characterize the extent to which clocks in different organs control systemic metabolic rhythms, an area that remains largely unexplored. We analyzed the metabolome of serum from mice with tissue-specific expression of the clock gene Bmal1. Having functional hepatic and muscle clocks can only drive a minority (13%) of systemic metabolic rhythms. Conversely, limiting Bmal1 expression to the central pacemaker in the brain restores rhythms to 57% of circulatory metabolites. Rhythmic feeding imposed on clockless mice resulted in a similar rescue, indicating that the central clock mainly regulates metabolic rhythms via behavior. These findings explicate the circadian communication between tissues and highlight the importance of the central clock in governing those signals.

DOI: https://doi.org/10.1126/sciadv.abo2896

FEBS Lett. 2022 Jul 01.

How circadian clocks keep time: the discovery of slowness.

DOI: https://doi.org/10.1002/1873-3468.14432

Cell Rep. 2022 Jun 28. pii: S2211-1247(22)00807-5. [Epub ahead of print]39(13): 111018

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

Stefan Tholen, Roma Patel, Agnieszka Agas, Kyle M Kovary, Atefeh Rabiee, Hayley T Nicholls, Ewa Bielczyk-Maczyńska, Wenting Yang, Fredric B Kraemer, Mary N Teruel.

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.

Keywords: CP: Metabolism; Cd36; brown adipose tissue; circadian rhythm; glucocorticoids; hormone oscillations; lipid metabolism; obesity; stress; white adipose tissue

DOI: https://doi.org/10.1016/j.celrep.2022.111018