GDF15 is still a mystery hormone

Casper M Sigvardsen; Michael M Richter; Sarah Engelbeen; Maximilian Kleinert; Erik A Richter

doi:10.1016/j.tem.2024.09.002

GDF15 is still a mystery hormone

Trends Endocrinol Metab. 2024 Oct 29:S1043-2760(24)00254-6. doi: 10.1016/j.tem.2024.09.002. Online ahead of print.

Authors

Casper M Sigvardsen¹, Michael M Richter², Sarah Engelbeen³, Maximilian Kleinert⁴, Erik A Richter⁵

Affiliations

¹ Department of Nutrition, Exercise and Sports, Faculty of Science, University of Copenhagen, Denmark.
² Department of Clinical Biochemistry, Copenhagen University Hospital Bispebjerg and Frederiksberg, Copenhagen, Denmark; Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
³ Department of Molecular Physiology of Exercise and Nutrition, German Institute of Human Nutrition (DIfE), Potsdam-Rehbruecke, Nuthetal, Germany; German Center for Diabetes Research (DZD), 85764 Munich-Neuherberg, Germany.
⁴ Department of Molecular Physiology of Exercise and Nutrition, German Institute of Human Nutrition (DIfE), Potsdam-Rehbruecke, Nuthetal, Germany; German Center for Diabetes Research (DZD), 85764 Munich-Neuherberg, Germany; Institute of Nutrition Science, University of Potsdam, Nuthetal, Germany. Electronic address: Maximilian.Kleinert@dife.de.
⁵ Department of Nutrition, Exercise and Sports, Faculty of Science, University of Copenhagen, Denmark. Electronic address: erichter@nexs.ku.dk.

PMID: 39472228
DOI: 10.1016/j.tem.2024.09.002

Abstract

Growth differentiation factor 15 (GDF15) is a member of the transforming growth factor-β (TGF-β) superfamily. Despite its identification over 20 years ago, the functions of GDF15 remain complex and not fully elucidated. Its concentration in plasma varies widely depending on the physiological and pathophysiological state of the organism. GDF15 has been described to regulate food intake and insulin sensitivity in rodents via the GDNF family receptor α-like (GFRAL) receptor, and to be elevated in pregnancy and many disease states and decreased in physically fit individuals. We discuss the latest developments in the regulation of GDF15 secretion and its diverse physiological effects, and touch upon possible GFRAL-independent effects of GDF15. In addition, we discuss the effects of proteins and peptides derived from the same precursor protein as GDF15.

Keywords: appetite; energy expenditure; insulin sensitivity; weight loss.

Publication types

Review