Liver Clock Protein BMAL1 Promotes de Novo Lipogenesis through Insulin-mTORC2-AKT 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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