Howard Hughes Medical Institute, Department of Developmental Biology, Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, United States.
Chan-Zuckerberg Biohub, San Francisco, United States.
Elife. 2023 Jan 31;12:e82311. doi: 10.7554/eLife.82311.
Nutrient availability fluctuates in most natural populations, forcing organisms to undergo periods of fasting and re-feeding. It is unknown how dietary changes influence liver homeostasis. Here, we show that a switch from ad libitum feeding to intermittent fasting (IF) promotes rapid hepatocyte proliferation. Mechanistically, IF-induced hepatocyte proliferation is driven by the combined action of systemic FGF15 and localized WNT signaling. Hepatocyte proliferation during periods of fasting and re-feeding re-establishes a constant liver-to-body mass ratio, thus maintaining the hepatostat. This study provides the first example of dietary influence on adult hepatocyte proliferation and challenges the widely held view that liver tissue is mostly quiescent unless chemically or mechanically injured.
营养物质的可获得性在大多数自然种群中波动，迫使生物经历禁食和再进食的时期。目前尚不清楚饮食变化如何影响肝脏内稳态。在这里，我们表明，从随意进食到间歇性禁食（IF）的转变会促进肝细胞快速增殖。从机制上讲，IF 诱导的肝细胞增殖是由全身 FGF15 和局部 WNT 信号的共同作用驱动的。在禁食和再进食期间，肝细胞增殖重新建立了恒定的肝体比，从而维持了肝稳态。这项研究提供了饮食对成年肝细胞增殖影响的第一个例子，挑战了肝脏组织在化学或机械损伤之前主要处于静止状态的普遍观点。
