CD36 regulates diurnal glucose metabolism and hepatic clock to maintain glucose homeostasis in mice

The mammalian circadian clock and glucose metabolism are highly intercon-nected, and disruption of this coupling is associated with multiple negative health outcomes. Liver is the major source of endogenous glucose production and liver clock is one of the most vital peripheral clock systems. We demonstrate that fatty acid translocase (CD36) is expressed rhythmically in mouse liver and autono-mously modulates the diurnal oscillations of liver clock and glucose homeostasis. CD36 knockout in hepatocytes inhibits the relay of insulin signaling and provokes FoxO1 nuclear shuttling, consequently increasing Per1 nuclear expression. More-over, FoxO1 can activate the central clock gene Per1 at the transcriptional level. These changes lead to a disrupted clock oscillation and behavioral rhythm. Our study first reveal that CD36 is a key regulator of the circadian oscillator and its deficiency may cause liver clock disruption, which aggravates the imbalance of glucose homeostasis and contribute to augmentation and progression of meta-bolic disease.

Automated summary

The mammalian circadian clock and glucose metabolism are closely related, and disruption of this connection has negative health outcomes. The liver is a major source of endogenous glucose production and has an important peripheral clock system. This study shows that CD36 regulates the liver clock and glucose homeostasis. Knockout of CD36 in hepatocytes inhibits insulin signaling and activates FoxO1, resulting in disrupted clock oscillation and behavioral rhythm.