Cold exposure increases circulating fibroblast growth factor 21 in the evening in males and females

in Endocrine Connections
Authors:
Carlijn Hoekx C Hoekx, Division of Endocrinology, Department of Medicine, Leiden University Medical Center, Leiden, Netherlands

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Borja Martinez-Tellez B Martinez-Tellez, Division of Endocrinology, Department of Medicine, Leiden University Medical Center, Leiden, Netherlands

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Maaike E. Straat M Straat, Division of Endocrinology, Department of Medicine, Leiden University Medical Center, Leiden, Netherlands

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Magdalena Verkleij M Verkleij, Division of Endocrinology, Department of Medicine, Leiden University Medical Center, Leiden, Netherlands

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Mirjam Kemmeren M Kemmeren, Division of Endocrinology, Department of Medicine, Leiden University Medical Center, Leiden, Netherlands

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Sander Kooijman S Kooijman, Division of Endocrinology, Department of Medicine, LUMC, Leiden, Netherlands

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Martin Uhrbom M Uhrbom, Bioscience Metabolism, Research and Early Development, Cardiovascular, Renal and Metabolism (CVRM), BioPharmaceuticals RandD, AstraZeneca in Gothenburg, Molndal, Sweden

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Saskia C.A. de Jager S de Jager, Laboratory of Experimental Cardiology, University Medical Centre Utrecht, Utrecht, Netherlands

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Patrick Rensen P Rensen, Division of Endocrinology, Department of Medicine, Leiden University Medical Center, Leiden, Netherlands

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Mariëtte Boon M Boon, Division of Endocrinology, Department of Medicine, LUMC, Leiden, Netherlands

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Correspondence: Carlijn Hoekx, Email: c.a.hoekx@lumc.nl
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Objectives: Cold exposure is linked to cardiometabolic benefits. Cold activates brown adipose tissue (BAT), increases energy expenditure, and induces secretion of the hormones fibroblast growth factor 21 (FGF21) and growth differentiation factor 15 (GDF15). The cold-induced increase in energy expenditure exhibits a diurnal rhythm in men. Therefore, we aimed to investigate the effect of cold exposure on serum FGF21 and GDF15 levels in humans and whether cold-induced changes in FGF21 and GDF15 levels differ between morning and evening in males and females.

Method: In this randomized cross-over study, serum FGF21 and GDF15 levels were measured in healthy lean males (n=12) and females (n=12) before, during, and after 90 minutes of stable cold exposure in the morning (7:45am) and evening (7:45pm) with a one-day washout period in between.

Results: Cold exposure increased FGF21 levels in the evening compared to the morning both in males (+61% vs. -13%; P<0.001) and in females (+58% vs. +8%; P<0.001). In contrast, cold exposure did not significantly modify serum GDF15 levels, and no diurnal variation was found. Changes in FGF21 and GDF15 levels did not correlate with changes in cold-induced energy expenditure in the morning and evening.

Conclusion: Cold exposure increased serum FGF21 levels in the evening, but not in the morning, in both males and females. GDF15 levels were not affected by cold exposure. Thus, this study suggests that the timing of cold exposure may influence cold-induced changes in FGF21 levels but not GDF15 levels and seems to be independent of changes in energy expenditure.