| Title |
FGF21 is not required for glucose homeostasis, ketosis or tumour suppression associated with ketogenic diets in mice
|
|---|---|
| Published in |
Diabetologia, June 2015
|
| DOI | 10.1007/s00125-015-3668-7 |
| Pubmed ID | |
| Authors |
Kerstin Stemmer, Fabio Zani, Kirk M. Habegger, Christina Neff, Petra Kotzbeck, Michaela Bauer, Suma Yalamanchilli, Ali Azad, Maarit Lehti, Paulo J. F. Martins, Timo D. Müller, Paul T. Pfluger, Randy J. Seeley |
| Abstract |
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. 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. 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. 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. |
X Demographics
The data shown below were collected from the profiles of 6 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United States | 3 | 50% |
| United Kingdom | 1 | 17% |
| Unknown | 2 | 33% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 3 | 50% |
| Scientists | 2 | 33% |
| Practitioners (doctors, other healthcare professionals) | 1 | 17% |
Mendeley readers
The data shown below were compiled from readership statistics for 75 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United States | 1 | 1% |
| Germany | 1 | 1% |
| Unknown | 73 | 97% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Master | 17 | 23% |
| Student > Ph. D. Student | 7 | 9% |
| Professor > Associate Professor | 4 | 5% |
| Professor | 3 | 4% |
| Student > Bachelor | 3 | 4% |
| Other | 10 | 13% |
| Unknown | 31 | 41% |
| Readers by discipline | Count | As % |
|---|---|---|
| Agricultural and Biological Sciences | 14 | 19% |
| Medicine and Dentistry | 9 | 12% |
| Biochemistry, Genetics and Molecular Biology | 9 | 12% |
| Nursing and Health Professions | 4 | 5% |
| Neuroscience | 2 | 3% |
| Other | 5 | 7% |
| Unknown | 32 | 43% |
Attention Score in Context
This research output has an Altmetric Attention Score of 18. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 31 March 2022.
All research outputs
#1,882,470
of 24,071,024 outputs
Outputs from Diabetologia
#1,015
of 5,213 outputs
Outputs of similar age
#24,030
of 267,919 outputs
Outputs of similar age from Diabetologia
#12
of 81 outputs
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