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Stemmer, K. ; Zani, F. ; Habegger, K.M.* ; Neff, C. ; Kotzbeck, P. ; Bauer, M. ; Yalamanchilli, S. ; Azad, A.* ; Lehti, M.* ; Martins, P.J.* ; Müller, T.D. ; Pfluger, P.T. ; Seeley, R.J.*

FGF21 is not required for glucose homeostasis, ketosis or tumour suppression associated with ketogenic diets in mice.

Diabetologia 58, 2414-2423 (2015)
DOI PMC
Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
AIMS/HYPOTHESIS: Ketogenic diets (KDs) have increasingly gained attention as effective means for weight loss and potential adjunctive treatment of cancer. The metabolic benefits of KDs are regularly ascribed to enhanced hepatic secretion of fibroblast growth factor 21 (FGF21) and its systemic effects on fatty-acid oxidation, energy expenditure (EE) and body weight. Ambiguous data from Fgf21-knockout animal strains and low FGF21 concentrations reported in humans with ketosis have nevertheless cast doubt regarding the endogenous function of FGF21. We here aimed to elucidate the causal role of FGF21 in mediating the therapeutic benefits of KDs on metabolism and cancer. METHODS: We established a dietary model of increased vs decreased FGF21 by feeding C57BL/6J mice with KDs, either depleted of protein or enriched with protein. We furthermore used wild-type and Fgf21-knockout mice that were subjected to the respective diets, and monitored energy and glucose homeostasis as well as tumour growth after transplantation of Lewis lung carcinoma cells. RESULTS: Hepatic and circulating, but not adipose tissue, FGF21 levels were profoundly increased by protein starvation, independent of the state of ketosis. We demonstrate that endogenous FGF21 is not essential for the maintenance of normoglycaemia upon protein and carbohydrate starvation and is therefore not needed for the effects of KDs on EE. Furthermore, the tumour-suppressing effects of KDs were independent of FGF21 and, rather, driven by concomitant protein and carbohydrate starvation. CONCLUSIONS/INTERPRETATION: Our data indicate that the multiple systemic effects of KD exposure in mice, previously ascribed to increased FGF21 secretion, are rather a consequence of protein malnutrition.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Energy Expenditure ; Fibroblast Growth Factor 21 ; Glucose Homeostasis ; Ketogenic Diets ; Protein Starvation ; Tumour Suppression
Sprache englisch
Veröffentlichungsjahr 2015
HGF-Berichtsjahr 2015
ISSN (print) / ISBN 0012-186X
e-ISSN 1432-0428
Zeitschrift Diabetologia
Quellenangaben Band: 58, Heft: 10, Seiten: 2414-2423 Artikelnummer: , Supplement: ,
Verlag Springer
Verlagsort Berlin ; Heidelberg [u.a.]
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Diabetes and Obesity (IDO)
POF Topic(s) 30201 - Metabolic Health

90000 - German Center for Diabetes Research
Forschungsfeld(er) Helmholtz Diabetes Center
PSP-Element(e) G-502200-001
G-508400-002
G-501900-221
G-502294-001
PubMed ID 26099854
DOI 10.1007/s00125-015-3668-7
WOS ID WOS:000361538600025
Scopus ID 84942191180
Scopus ID 84932156980
Erfassungsdatum 2015-06-25
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