Matching the timing of brain and liver clocks helps protect against time-related metabolic diseases

Deletion of hepatocyte REV-ERBs in mice with disrupted circadian clocks rescues diet-induced obesity and hepatic fat accumulation.

• Circadian clocks in nearly every body cell are influenced by the central clock located in the suprachiasmatic nucleus (SCN).
• Desynchronization between the SCN and external light-dark cycles is linked to metabolic issues in shift workers.
• Mice lacking REV-ERBα/β receptors in the SCN show increased sensitivity to diet-induced obesity on a regular light-dark schedule.
• Mice with REV-ERBs deleted in liver cells experience worsened fat accumulation when exposed to a high-fat diet.
• Inducing deletion of hepatocyte REV-ERBs in SCN DKO mice mitigates diet-induced obesity and fat accumulation despite continued behavioral rhythm disruption.
• The findings indicate that synchronizing peripheral clocks to the central clock may help address metabolic disorders resulting from circadian misalignment.

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