Weight-loss maintenance is accompanied by interconnected alterations in circulating FGF21-adiponectin-leptin and bioactive sphingolipids
Research output: Contribution to journal › Journal article › Research › peer-review
Standard
Weight-loss maintenance is accompanied by interconnected alterations in circulating FGF21-adiponectin-leptin and bioactive sphingolipids. / Fiorenza, Matteo; Checa, Antonio; Sandsdal, Rasmus M.; Jensen, Simon B.K.; Juhl, Christian R.; Noer, Mikkel H.; Bogh, Nicolai P.; Lundgren, Julie R.; Janus, Charlotte; Stallknecht, Bente M.; Holst, Jens Juul; Madsbad, Sten; Wheelock, Craig E.; Torekov, Signe S.
In: Cell Reports Medicine, Vol. 5, No. 7, 101629, 2024.Research output: Contribution to journal › Journal article › Research › peer-review
Harvard
APA
Vancouver
Author
Bibtex
}
RIS
TY - JOUR
T1 - Weight-loss maintenance is accompanied by interconnected alterations in circulating FGF21-adiponectin-leptin and bioactive sphingolipids
AU - Fiorenza, Matteo
AU - Checa, Antonio
AU - Sandsdal, Rasmus M.
AU - Jensen, Simon B.K.
AU - Juhl, Christian R.
AU - Noer, Mikkel H.
AU - Bogh, Nicolai P.
AU - Lundgren, Julie R.
AU - Janus, Charlotte
AU - Stallknecht, Bente M.
AU - Holst, Jens Juul
AU - Madsbad, Sten
AU - Wheelock, Craig E.
AU - Torekov, Signe S.
N1 - Publisher Copyright: © 2024 The Authors
PY - 2024
Y1 - 2024
N2 - 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.
AB - 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.
KW - adiponectin
KW - ceramide
KW - cytokines
KW - exercise
KW - FGF21
KW - GDF15
KW - GLP-1 receptor agonist
KW - leptin
KW - obesity
KW - sphingolipids
U2 - 10.1016/j.xcrm.2024.101629
DO - 10.1016/j.xcrm.2024.101629
M3 - Journal article
C2 - 38959886
AN - SCOPUS:85197238748
VL - 5
JO - Cell Reports Medicine
JF - Cell Reports Medicine
SN - 2666-3791
IS - 7
M1 - 101629
ER -
ID: 398356725