Weight-loss maintenance is accompanied by interconnected alterations in circulating FGF21-adiponectin-leptin and bioactive sphingolipids.

Autor:	Fiorenza M; Department of Biomedical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark. Electronic address: matteo.fiorenza@sund.ku.dk., Checa A; Unit of Integrative Metabolomics, Institute of Environmental Medicine, Karolinska Institutet, 17177 Stockholm, Sweden., Sandsdal RM; Department of Biomedical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark., Jensen SBK; Department of Biomedical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark., Juhl CR; Department of Biomedical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark., Noer MH; Department of Biomedical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark., Bogh NP; Department of Biomedical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark., Lundgren JR; Department of Biomedical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark., Janus C; Department of Biomedical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark., Stallknecht BM; Department of Biomedical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark., Holst JJ; Department of Biomedical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark; Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, 2200 Copenhagen, Denmark., Madsbad S; Department of Endocrinology, Copenhagen University Hospital-Amager and Hvidovre, 2650 Hvidovre, Denmark., Wheelock CE; Unit of Integrative Metabolomics, Institute of Environmental Medicine, Karolinska Institutet, 17177 Stockholm, Sweden; Department of Respiratory Medicine and Allergy, Karolinska University Hospital, 17177 Stockholm, Sweden., Torekov SS; Department of Biomedical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark. Electronic address: torekov@sund.ku.dk.
Jazyk:	angličtina
Zdroj:	Cell reports. Medicine [Cell Rep Med] 2024 Jul 16; Vol. 5 (7), pp. 101629. Date of Electronic Publication: 2024 Jul 02.
DOI:	10.1016/j.xcrm.2024.101629
Abstrakt:	Weight loss is often followed by weight regain. Characterizing endocrine alterations accompanying weight reduction and regain may disentangle the complex biology of weight-loss maintenance. Here, we profile energy-balance-regulating metabokines and sphingolipids in adults with obesity undergoing an initial low-calorie diet-induced weight loss and a subsequent weight-loss maintenance phase with exercise, glucagon-like peptide-1 (GLP-1) analog therapy, both combined, or placebo. We show that circulating growth differentiation factor 15 (GDF15) and C16:0-C18:0 ceramides transiently increase upon initial diet-induced weight loss. Conversely, circulating fibroblast growth factor 21 (FGF21) is downregulated following weight-loss maintenance with combined exercise and GLP-1 analog therapy, coinciding with increased adiponectin, decreased leptin, and overall decrements in ceramide and sphingosine-1-phosphate levels. Subgroup analyses reveal differential alterations in FGF21-adiponectin-leptin-sphingolipids between weight maintainers and regainers. Clinically, cardiometabolic health outcomes associate with selective metabokine-sphingolipid remodeling signatures. Collectively, our findings indicate distinct FGF21, GDF15, and ceramide responses to diverse phases of weight change and suggest that weight-loss maintenance involves alterations within the metabokine-sphingolipid axis. Competing Interests: Declaration of interests A family member of R.M.S. holds Novo Nordisk stocks. S.M. is on advisory boards of AstraZeneca, Boehringer Ingelheim, Eli Lilly, Merck Sharp & Dohme, Novo Nordisk, and Sanofi Aventis; receives lecture fees from AstraZeneca, Boehringer Ingelheim, Merck Sharp & Dohme, Novo Nordisk, and Sanofi Aventis; and is a research grant recipient from Novo Nordisk and Boehringer Ingelheim. J.J.H. is on the advisory board of Novo Nordisk. S.S.T. is a research grant recipient and receives lecture fees from Novo Nordisk. (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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