Liver clock protein BMAL1 supports new fat creation through insulin and cell growth signaling

Deficiency in the clock protein BMAL1 reduces lipogenic gene expression and de novo lipogenesis in the liver.

• Both global and acute liver-specific Bmal1 deficiency resulted in decreased expression of genes involved in lipid synthesis upon refeeding.
• Bmal1 overexpression in mouse liver increased mRNA levels of lipogenic enzymes.
• Primary mouse hepatocytes lacking Bmal1 showed reduced levels of both de novo lipogenesis and lipogenic enzymes.
• Impaired AKT activation was observed in refed mouse liver and insulin-treated primary hepatocytes with Bmal1 deficiency.
• Restoration of AKT activity in Bmal1(-/-) hepatocytes nearly normalized de novo lipogenesis.
• Bmal1 deficiency or knockdown led to decreased levels of RICTOR, a key component of the mTORC2 complex.

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