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. 2024 Nov 8;386(6722):673-677.
doi: 10.1126/science.adn2786. Epub 2024 Nov 7.

Hepatic vagal afferents convey clock-dependent signals to regulate circadian food intake

Lauren N Woodie  1   2 , Lily C Melink  1   2 , Mohit Midha  1   2 , Alan M de Araújo  3 , Caroline E Geisler  4 , Ahren J Alberto  1   2 , Brianna M Krusen  1   2 , Delaine M Zundell  1   2 , Guillaume de Lartigue  3   5 , Matthew R Hayes  1   4 , Mitchell A Lazar  1   2
Affiliations

Hepatic vagal afferents convey clock-dependent signals to regulate circadian food intake

Lauren N Woodie et al. Science. .

Abstract

Circadian desynchrony induced by shiftwork or jet lag is detrimental to metabolic health, but how synchronous or desynchronous signals are transmitted among tissues is unknown. We report that liver molecular clock dysfunction is signaled to the brain through the hepatic vagal afferent nerve (HVAN), leading to altered food intake patterns that are corrected by ablation of the HVAN. Hepatic branch vagotomy also prevents food intake disruptions induced by high-fat diet feeding and reduces body weight gain. Our findings reveal a homeostatic feedback signal that relies on communication between the liver and the brain to control circadian food intake patterns. This identifies the hepatic vagus nerve as a potential therapeutic target for obesity in the setting of chronodisruption.

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Conflict of interest statement

Competing interests: The authors declare the following competing interests: MAL is on the advisory board and has received research funding unrelated to these studies from Pfizer, serves on the advisory board and is co-founder of Flare Therapeutics, and has consulted for Madrigal Pharmaceuticals. MRH receives additional research funding from Boehringer Ingelheim, Novo Nordisk, Pfizer, Gila Therapeutics, and Eli Lilly & Co. that was not used in support of these studies. LNW, LCM, MM, AMA, CEG, AJA, BMK, DMZ, and GL have no competing interests to declare.

Update of

Comment in

  • Rhythmic liver drives feeding behavior.
    Martinez-Sanchez N, Ray D. Martinez-Sanchez N, et al. Science. 2024 Nov 8;386(6722):622-623. doi: 10.1126/science.adt0743. Epub 2024 Nov 7. Science. 2024. PMID: 39509522

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