Toward reconciling the roles of FGF21 in protein appetite, sweet preference, and energy expenditure

Samantha M Solon-Biet; Ximonie Clark; Kim Bell-Anderson; Patricia M Rusu; Ruth Perks; Therese Freire; Tamara Pulpitel; Alistair M Senior; Andrew J Hoy; Okka Aung; David G Le Couteur; David Raubenheimer; Adam J Rose; Arthur D Conigrave; Stephen J Simpson

doi:10.1016/j.celrep.2023.113536

Toward reconciling the roles of FGF21 in protein appetite, sweet preference, and energy expenditure

Cell Rep. 2023 Dec 26;42(12):113536. doi: 10.1016/j.celrep.2023.113536. Epub 2023 Dec 5.

Authors

Affiliations

¹ Charles Perkins Centre, The University of Sydney, Sydney, NSW 2006, Australia; School of Life and Environmental Sciences, Faculty of Science, The University of Sydney, Sydney, NSW 2006, Australia; School of Medicine, The University of Notre Dame, Darlinghurst, NSW 2010, Australia. Electronic address: samantha.biet@sydney.edu.au.
² Charles Perkins Centre, The University of Sydney, Sydney, NSW 2006, Australia; School of Life and Environmental Sciences, Faculty of Science, The University of Sydney, Sydney, NSW 2006, Australia.
³ Department of Biochemistry and Molecular Biology, Metabolism, Diabetes and Obesity Program, Biomedicine Discovery Institute, Monash University, Clayton, VIC 3800, Australia.
⁴ Charles Perkins Centre, The University of Sydney, Sydney, NSW 2006, Australia; Sydney Medical School, Faculty of Health and Medicine, The University of Sydney, Sydney, NSW 2006, Australia.
⁵ Charles Perkins Centre, The University of Sydney, Sydney, NSW 2006, Australia; School of Medical Sciences, Faculty of Health and Medicine, The University of Sydney, Sydney, NSW 2006, Australia.
⁶ Charles Perkins Centre, The University of Sydney, Sydney, NSW 2006, Australia; Sydney Medical School, Faculty of Health and Medicine, The University of Sydney, Sydney, NSW 2006, Australia; Ageing and Alzheimer's Institute and Centre for Education and Research on Ageing, Concord Hospital, Concord, NSW 2139, Australia.
⁷ Charles Perkins Centre, The University of Sydney, Sydney, NSW 2006, Australia; School of Life and Environmental Sciences, Faculty of Science, The University of Sydney, Sydney, NSW 2006, Australia; Department of Endocrinology, Royal Prince Alfred Hospital, Camperdown, NSW 2050 Australia.
⁸ Charles Perkins Centre, The University of Sydney, Sydney, NSW 2006, Australia; School of Life and Environmental Sciences, Faculty of Science, The University of Sydney, Sydney, NSW 2006, Australia. Electronic address: stephen.simpson@sydney.edu.au.

PMID: 38060447
DOI: 10.1016/j.celrep.2023.113536

Abstract

Fibroblast growth factor 21 (FGF21), an endocrine signal robustly increased by protein restriction independently of an animal's energy status, exerts profound effects on feeding behavior and metabolism. Here, we demonstrate that considering the nutritional contexts within which FGF21 is elevated can help reconcile current controversies over its roles in mediating macronutrient preference, food intake, and energy expenditure. We show that FGF21 is primarily a driver of increased protein intake in mice and that the effect of FGF21 on sweet preference depends on the carbohydrate balance of the animal. Under no-choice feeding, FGF21 infusion either increased or decreased energy expenditure depending on whether the animal was fed a high- or low-energy diet, respectively. We show that while the role of FGF21 in mediating feeding behavior is complex, its role in promoting protein appetite is robust and that the effects on sweet preference and energy expenditure are macronutrient-state-dependent effects of FGF21.

Keywords: CP: Metabolism.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Appetite*
Energy Metabolism
Feeding Behavior
Fibroblast Growth Factors* / metabolism
Liver / metabolism
Mice

Substances

fibroblast growth factor 21
Fibroblast Growth Factors