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Intermittent fasting induces rapid hepatocyte proliferation to maintain the hepatostat

ABSTRACT: Nutrient availability fluctuates in most natural populations, forcing organisms to undergo periods of fasting and re-feeding. It is unknown how dietary change influences 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 intestinally produced, systemic endocrine FGF15 and localized WNT signaling. IF proliferation re-establishes a constant liver-to-body-mass ratio during periods of fasting and re-feeding, a process termed 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.

ORGANISM(S): Mouse Mus Musculus

TISSUE(S): Liver

SUBMITTER: Brian DeFelice

PROVIDER: ST002263 | MetabolomicsWorkbench | Mon Aug 01 00:00:00 BST 2022

REPOSITORIES: MetabolomicsWorkbench

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