Mild cold exposure modulates fibroblast growth factor 21 (FGF21) diurnal rhythm in humans: relationship between FGF21 levels, lipolysis, and cold-induced thermogenesis
Lee P, Brychta RJ, Linderman J, Smith S, Chen KY, Celi FS
The Journal of clinical endocrinology and metabolism · 119 citations
How it was studied
- Design
- Randomized controlled trial (indexed by PubMed)
- Studied in
- People
- Main outcome
- Health markers and function
Who paid for it
- Funding
- Independent funding
- Government
- National Institutes of Health
- Government
- National Institute of Diabetes and Digestive and Kidney Diseases
- Government
- NIDDK NIH HHS
- Government
- Intramural NIH HHS
- Grants
- National Institute of Diabetes and Digestive and Kidney Diseases (Z01-DK047057-01); National Institute of Diabetes and Digestive and Kidney Diseases (Z01-DK047057-02)
Based on 4 listed funder(s).
Publication
- Published
- 2012-11-14 · J Clin Endocrinol Metab · vol. 98 · issue 1 · pp. E98–E102
- Publisher
- Oxford University Press
- Cited
- 141 citations · more than 97% of similar papers · 5.5× the field average
- Impact
- Top 10% most cited in its field
- References
- 19 works
- Access
- Open access (repository copy)
- Research areas
- Fibroblast Growth Factor Research · Adipose Tissue and Metabolism · Adipokines, Inflammation, and Metabolic Diseases
- Keywords
- FGF21, Lipolysis, Thermogenesis, Internal medicine, Endocrinology, White adipose tissue, Adipose tissue, Area under the curve, Chemistry, Microdialysis, Brown adipose tissue, Biology, Medicine, Fibroblast growth factor
- MeSH
- humans, fibroblast growth factors, cross-over studies, single-blind method, lipolysis, thermogenesis, circadian rhythm, osmolar concentration, adult, middle aged, female, male, cold temperature, young adult
6 authors
From US
- Paul Lee · correspondingNational Institute of Diabetes and Digestive and Kidney Diseases
- Robert J. BrychtaNational Institutes of Health; National Institute of Diabetes and Digestive and Kidney Diseases
- Joyce D. LindermanNational Institutes of Health; National Institute of Diabetes and Digestive and Kidney Diseases
- Sheila SmithNational Institutes of Health; National Institute of Diabetes and Digestive and Kidney Diseases
- Kong Y. ChenNational Institutes of Health; National Institute of Diabetes and Digestive and Kidney Diseases
- Francesco Saverio CeliNational Institutes of Health; National Institute of Diabetes and Digestive and Kidney Diseases
Abstract
Context
Cold exposure stimulates fibroblast growth factor 21 (FGF21) secretion in animals, enhancing the cold-induced thermogenesis (CIT) response through browning of white adipose tissue. In humans, the effects of cold exposure on circulating FGF21 levels are unknown.
Objective
Our objective was to evaluate the effects of mild cold exposure on circulating FGF21 and its relationship with CIT and lipolysis in humans.
Design and setting
We conducted a randomized, single-blind, crossover intervention study at the National Institutes of Health Clinical Center.
Participants
Participants were healthy adults.
Intervention
Subjects were exposed to a 12-h exposure to 24 or 19 C in a whole-room indirect calorimeter.
Outcome measures
Energy expenditure, plasma FGF 21, nonesterified fatty acid, and adipose tissue microdialysis glycerol concentrations were evaluated.
Results
At 24 C, plasma FGF21 exhibited a diurnal rhythm, peaking at 0800 h [110 (59-178) pg/ml], and progressively dropped to a nadir at 1700 h [41 (21-71) pg/ml, P < 0.0001] before rising at 1900 h [60 (11-81) pg/ml, P < 0.0001]. Exposure at 19 C lessened the diurnal reduction of FGF21 observed at 24 C from 0800-1700 h and augmented overall FGF21 levels by 37 ± 45% (P = 0.01). The change in area under the curve plasma FGF21 between 19 and 24 C correlated positively with the change in area under the curve adipose microdialysate glycerol (R(2) = 0.35, P = 0.04) but not with nonesterified fatty acid. Cold-induced increase in FGF21 predicted greater rise in energy expenditure during cold exposure (β = 0.66, P = 0.027), independent of age, gender, fat mass, and lean mass.
Conclusions
Mild cold exposure increased circulating FGF21 levels, predicting greater lipolysis and CIT. A small reduction in environmental temperature is sufficient to modulate FGF21 diurnal rhythm in humans, which may mediate cold-induced metabolic changes similar to those in animals.
Abstract via Europe PMC. Copyright remains with the authors or publisher.
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