Circadian feeding rhythm loss drives sex-specific β-cell dysfunction in diet-induced obesity

In male C57BL/6 mice on an 8-week high-fat diet, circadian β-cell function is disrupted, with a 42.1% reduction in circadian-regulated islet transcripts versus chow.

• Why it matters: Diet-induced obesity is linked to impaired circadian glucose control, but how circadian β-cell rhythms and their transcriptional/epigenomic programs change—especially by sex—was unclear.
• What they did: Mice were exposed to chow or HFD, then feeding/activity, glucose tolerance, in vivo GSIS, RNA-seq, and ATAC-seq circadian rhythms were measured; time-restricted feeding (tRF) was applied in dark or light phases.
• The result: DIO abolished circadian regulation of glucose tolerance and GSIS in males (p<0.05 vs chow) while females maintained circadian homeostasis; dark-phase tRF restored tolerance, GSIS, and islet gene expression.

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