ArticleDiabetologia2015
FGF21 is not required for glucose homeostasis, ketosis or tumour suppression associated with ketogenic diets in mice.
Article in Diabetologia, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
30 citing papers in PubMed, 1 synthesis or guideline pooled it, 43 citations in OpenAlex.
- Cancer Treatment With the Ketogenic Diet: A Systematic Review and Meta-analysis of Animal Studies.Frontiers in nutrition · 2021Pooled it
- Fibroblast growth factor 21 as a circulating biomarker at various stages of colorectal carcinogenesis.British journal of cancer · 2018Trial
- Insulin-sensitizing effects of fibroblast growth factor-21 in underfed sheep.Journal of animal science · 2025Article
- FGF21 mediating the Sex-dependent Response to Dietary Macronutrients.The Journal of clinical endocrinology and metabolism · 2024Review
- Beta hydroxybutyrate induces lung cancer cell death, mitochondrial impairment and oxidative stress in a long term glucose-restricted condition.Molecular biology reports · 2024Article
- Signals of energy availability in sleep: consequences of a fat-based metabolism.Frontiers in nutrition · 2024Review
- [GPR109A partly mediates inhibitory effects of β-hydroxybutyric acid on lung adenocarcinoma cell proliferation, migration and invasion].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2023Article
- Sex-specific differences in metabolic hormone and adipose tissue dynamics induced by moderate low-carbohydrate and ketogenic diet.Scientific reports · 2023Article
- Triple Therapy with Metformin, Ketogenic Diet, and Metronomic Cyclophosphamide Reduced Tumor Growth in MYCN-Amplified Neuroblastoma Xenografts.Metabolites · 2023Article
- Adipocyte-derived extracellular vesicles increase insulin secretion through transport of insulinotropic protein cargo.Nature communications · 2023Article
- Fibroblast Growth Factor 21 Facilitates the Homeostatic Control of Feeding Behavior.Journal of clinical medicine · 2022Review
- Hepatic FGF21: Its Emerging Role in Inter-Organ Crosstalk and Cancers.International journal of biological sciences · 2022Review
- Short-Term Ketogenic Diet Induces a Molecular Response That Is Distinct From Dietary Protein Restriction.Frontiers in nutrition · 2022Article
- Protein Appetite at the Interface between Nutrient Sensing and Physiological Homeostasis.Nutrients · 2021Review
- Ketogenic Diet in Cancer Prevention and Therapy: Molecular Targets and Therapeutic Opportunities.Current issues in molecular biology · 2021Review
- The Nuanced Metabolic Functions of Endogenous FGF21 Depend on the Nature of the Stimulus, Tissue Source, and Experimental Model.Frontiers in endocrinology · 2021Review
- FGF21 and the Physiological Regulation of Macronutrient Preference.Endocrinology · 2020Review
- Ketogenic diet in the treatment of cancer - Where do we stand?Molecular metabolism · 2020Review
- Fibroblast Growth Factor-21 Controls Dietary Protein Intake in Male Mice.Endocrinology · 2019Article
- Fasting and cancer: molecular mechanisms and clinical application.Nature reviews. Cancer · 2018Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 6 institutions in 3 countries.
Funding
Abstract
aims/hypothesisKetogenic 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.
methodsWe 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.
resultsHepatic 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/
interpretationOur 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.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.