SREBP1 acts downstream of the body clock to influence fatty liver development caused by a high-fat diet

Hepatic circadian factor CLOCK may influence metabolic dysfunction-associated fatty liver disease (MAFLD) through its regulation of SREBP1.

• High-fat diet led to increased body weight and liver fat in male mice.
• CLOCK levels were significantly lower in the liver, disrupting lipid metabolism.
• The gene Srebf1, which encodes the transcription factor SREBP1, was up-regulated with lower CLOCK levels.
• In cellular models, reducing CLOCK increased SREBP1 and lipid accumulation, while over-expressing CLOCK had the opposite effect.
• In vivo, boosting CLOCK levels decreased liver triglycerides and cholesterol, reducing hepatic steatosis.
• SREBP1 signaling may be a key target of CLOCK in the development of MAFLD.

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