Weight-loss maintenance is accompanied by interconnected alterations in circulating FGF21-adiponectin-leptin and bioactive sphingolipids
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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.
Originalsprog | Engelsk |
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Artikelnummer | 101629 |
Tidsskrift | Cell Reports Medicine |
Vol/bind | 5 |
Udgave nummer | 7 |
Antal sider | 22 |
ISSN | 2666-3791 |
DOI | |
Status | Udgivet - 2024 |
Bibliografisk note
Funding Information:
We thank all the study participants. The study received financial support from multiple sources, including an Excellence grant from the Novo Nordisk Foundation ( NNF16OC0019968 ), a grant from the Novo Nordisk Foundation Center for Basic Metabolic Research , a grant from the Novo Nordisk Foundation Tripartite Immunometabolism Consortium ( NNF15CC0018486 ), as well as funding from Helsefonden , the Danish Diabetes Academy , the Faculty of Health and Medical Sciences at the University of Copenhagen , and the Department of Biomedical Sciences at the University of Copenhagen . C.E.W. received support from the Swedish Heart-Lung Foundation ( HLF 20200693 and HLF 20210519 ) and the Swedish Research Council ( 2022-00796 ). Novo Nordisk A/S provided Saxenda (liraglutide) and placebo pens, while Cambridge Weight Plan supplied low-calorie meal replacement products. Novo Nordisk A/S and Cambridge Weight Plan were not involved in the conceptualization and design of the study, data collection, data analysis and interpretation, or preparation of the manuscript.
Publisher Copyright:
© 2024 The Authors
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