The DOI matches its Crossref record; 28 of the 45 references it cites were found in a registry or an index.
Circulating Fibroblast Growth Factor 21 Is Induced by Peroxisome Proliferator-Activated Receptor Agonists But Not Ketosis in Man
Abstract
CONTEXT: Murine fibroblast growth factor (FGF) 21 is a nutritionally regulated hormone secreted by the liver principally in response to peroxisome proliferator-activated receptor-alpha (PPAR alpha) activation, which plays a critical role in regulating metabolism during ketosis. FGF21 is also a PPAR gamma target gene in mouse adipose tissue. Little information is available on FGF21 functions in humans. OBJECTIVE: The aim of the study was to measure plasma FGF21 during fasting, ketogenic diet, and PPAR agonist treatment in humans. DESIGN AND SETTING: We conducted a prospective study involving three patient groups at two university hospitals. PATIENTS: Eight healthy male volunteers underwent a 48-h period of starvation followed by 24-h refeeding (group 1); seven obese individuals were allocated to a low-carbohydrate diet for 3 months (group 2); and three groups of healthy, overweight or obese male volunteers received treatment with a PPAR alpha (20 microg/d GW590735) (n=6), PPAR delta (10 mg/d GW501516) (n=6), or PPAR gamma agonist (rosiglitazone) (n=10) for 2 wk (group 3). MAIN OUTCOME MEASURES: Fasting plasma FGF21 and serum 3-hydroxybutyrate were measured. RESULTS: There was no significant variation in human plasma FGF21 during fasting and refeeding. A 3-month ketogenic diet was associated with a 42% decline in plasma FGF21 levels. Circulating FGF21 increased significantly in response to treatment with PPAR alpha (39%) and PPAR delta (32%), but not PPAR gamma agonists. CONCLUSION: FGF21 does not play a major role in regulating the fasting response or ketosis in man. However, plasma FGF21 is elevated in response to pharmacological activation of PPAR alpha and PPAR delta and may contribute to the beneficial metabolic effects observed in response to pharmacotherapy with these compounds.
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In the citing paper
“ketogenic diets do not induce plasma FGF21 levels in humans26,30,34”
From Metabolic messengers: FGF21 (2021) · cites this paper as [34]
In the citing paper
“Importantly, it is unclear whether there is any translational relevance of FGF21 to the beneficial effects of ketogenic diets in humans because circulating FGF21 levels fail to increase in humans in response to a ketogenic diet (19, 42, 73).”
From Fibroblast Growth Factor 21: A Versatile Regulator of Metabolic Homeostasis (2018) · cites this paper as [19]
In the citing paper
“The effect of fasting and ketogenic diets to increase FGF21 is not nearly as robust in humans as initially observed in mice”
From FGF21 and the physiological regulation of macronutrient preference (2020) · cites this paper as [131]
Citations
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Understanding the Physiology of FGF21
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PPARs in Obesity-Induced T2DM, Dyslipidaemia and NAFLD
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Metadata
- Authors
- Christodoulides, C., Dyson, P., Sprecher, D., Tsintzas, K., & Karpe, F.
- Affiliations
- Churchill Hospital (GB)
- GlaxoSmithKline (United States) (US)
- University of Nottingham (GB)
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 2009-09-01
- Volume
- 94
- Issue
- 9
- Pages
- 3594-3601
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- OpenAlex
- W2140313261
- Cited by
- 153
- References
- 45
- Citations by year
- 2026: 5 · 2025: 7 · 2024: 8 · 2023: 6 · 2022: 11 · 2021: 11 · 2020: 8 · 2019: 12 · 2018: 11 · 2017: 9 · 2016: 12 · 2015: 6 · 2014: 9 · 2013: 4 · 2012: 13
- FWCI
- 4.57
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Funders
- GlaxoSmithKline
- Wellcome Trust
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fibroblast Growth Factor Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
- Health Sciences › Medicine › Physiology (medical) › Dietary Effects on Health
- Keywords
- FGF21, PPARα agonist, PPARδ agonist, PPARγ agonists, ketosis, ketogenic diet, fasting and refeeding, beta-hydroxybutyrate, GW501516, rosiglitazone, obesity, metabolic regulation
- MeSH terms
- Adult, Fibroblast Growth Factors, Humans, Ketosis, Male, Prospective Studies, Peroxisome Proliferator-Activated Receptors, Diet, Ketogenic
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