Proceedings of the National Academy of Sciences, Год журнала: 2024, Номер 121(51)

Опубликована: Дек. 12, 2024

Nearly every cell of the body contains a circadian clock mechanism that is synchronized with light-entrained in suprachiasmatic nucleus (SCN). Desynchrony between SCN and external environment leads to metabolic dysfunction shift workers. Similarly, mice markedly shortened endogenous period due deletion REV-ERBα/β nuclear receptors (SCN DKO) exhibit increased sensitivity diet-induced obesity (DIO) on 24 h light:dark cycle while REV-ERBs deleted hepatocytes (HepDKO) display exacerbated hepatosteatosis response high-fat diet. Here, we show inducing hepatocyte DKO (Hep-SCN DDKO) rescued DIO hepatic triglyceride accumulation, without affecting behavioral period. These findings suggest disturbances environmental desynchrony central are effects peripheral clocks which can be mitigated by matching periods even desynchronous environment. Thus, maintaining synchrony within an organism, rather than exogenous clocks, may viable target for treatment disorders associated disruption.

Язык: Английский