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

Mengyue Chen; Yang Zhang; Shu Zeng; Danyang Li; Mengyue You; Mingyang Zhang; Zhenyu Wang; Li Wei; Yaxi Chen; Xiong Z Ruan

doi:10.1016/j.isci.2023.106524

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

iScience. 2023 Mar 29;26(4):106524. doi: 10.1016/j.isci.2023.106524. eCollection 2023 Apr 21.

Authors

Mengyue Chen¹, Yang Zhang¹, Shu Zeng¹, Danyang Li¹, Mengyue You¹, Mingyang Zhang¹, Zhenyu Wang¹, Li Wei¹, Yaxi Chen¹, Xiong Z Ruan^{1

2}

Affiliations

¹ Centre for Lipid Research & Chongqing Key Laboratory of Metabolism on Lipid and Glucose, Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, Department of Infectious Diseases, the Second Affiliated Hospital, Chongqing Medical University, Chongqing 400016, China.
² John Moorhead Research Laboratory, Centre for Nephrology, University College London Medical School, Royal Free Campus, University College London, London NW3 2PF, UK.

Abstract

The mammalian circadian clock and glucose metabolism are highly interconnected, 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 autonomously 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. Moreover, 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 metabolic disease.

Keywords: Endocrinology; Hepatology; Molecular biology.