Hepatic gene therapy rescues high-fat diet responses in circadian Clock mutant mice

Nighttime-restricted feeding restored food intake in mutant mice, but did not regulate body weight under a high-fat diet.

• Mutant mice exhibited metabolic dysregulation linked to disrupted circadian appetite control.
• Liver-directed gene therapy partially restored circadian function in mutant mice, affecting metabolic regulation.
• Mutant mice with restored liver clock function showed normalized food intake rhythms and energy expenditure.
• Decreased nighttime leptin and daytime ghrelin levels were observed in mutant mice with improved liver clock function.
• Restoration of liver clock function was associated with reduced hepatic lipid accumulation and improved glucose tolerance.

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