Liver–gut axis signaling regulates circadian energy metabolism in shift workers

作者：Zhenning Yang, Helmut Zarbl, Bo Kong, Rulaiha E. Taylor, Kathleen Black, Howard M. Kipen, Veronia Basaly, Mingzhu Fang, Grace Liejun Guo · 发表于：The FASEB Journal · 年份：2024 · DOI：10.1096/fj.202402102r · 被引用次数：16 · 研究领域：Circadian rhythm and melatonin、Dietary Effects on Health、Sleep and Wakefulness Research

Abstract Circadian rhythm is critical to maintaining the whole‐body metabolic homeostasis of an organism. Chronic disruption of circadian rhythm by shift work is an important risk factor for metabolic diseases. Fibroblast growth factor 15/19 (FGF15/19), a key component in the liver–gut axis, potently suppresses bile acid (BA) synthesis and improves insulin sensitivity. FGF15/19 emerges as a novel pharmaceutical target for prevention and treatment of metabolic diseases. The nicotinamide adenine dinucleotide (NAD + )‐dependent sirtuin 1 (SIRT1) deacetylase plays an important role in the maintenance of hepatic homeostasis by linking hepatic metabolism to circadian rhythm. Here, our clinical study identified that circadian rhythmicity and levels of plasma FGF19 and BA profiling, and cellular NAD + ‐dependent SIRT1 signaling were disturbed in night shift (NS, n = 10) compared to day shift (DS, n = 12) nurses. Our in vitro data showed that recombinant FGF19 protein rescued cellular circadian rhythm disrupted by SIRT1 inhibitors. Furthermore, we determined the effect of FGF15 on circadian rhythm and hepatic metabolism in wild‐type (WT), Fgf15 knockout (KO), and Fgf15 transgenic (TG) mice. The expressions of circadian‐controlled genes (CCGs) involved in SIRT1 signaling, BA and lipid metabolism, and inflammation were disrupted in Fgf15 KO compared to WT and/or Fgf15 TG mice. Moreover, systemic FGF15 deficiency led to the circadian disturbance of NAD + ‐dependent SIRT1 signaling and si...