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

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          Abstract

          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 min of stable cold exposure in the morning (07:45 h) and evening (19:45 h) with a 1-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.

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          Most cited references42

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          World Medical Association Declaration of Helsinki: ethical principles for medical research involving human subjects.

          (2013)
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            The Human Cell Atlas

            The recent advent of methods for high-throughput single-cell molecular profiling has catalyzed a growing sense in the scientific community that the time is ripe to complete the 150-year-old effort to identify all cell types in the human body. The Human Cell Atlas Project is an international collaborative effort that aims to define all human cell types in terms of distinctive molecular profiles (such as gene expression profiles) and to connect this information with classical cellular descriptions (such as location and morphology). An open comprehensive reference map of the molecular state of cells in healthy human tissues would propel the systematic study of physiological states, developmental trajectories, regulatory circuitry and interactions of cells, and also provide a framework for understanding cellular dysregulation in human disease. Here we describe the idea, its potential utility, early proofs-of-concept, and some design considerations for the Human Cell Atlas, including a commitment to open data, code, and community.
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              Brown adipose tissue as a secretory organ.

              Brown adipose tissue (BAT) is the main site of adaptive thermogenesis and experimental studies have associated BAT activity with protection against obesity and metabolic diseases, such as type 2 diabetes mellitus and dyslipidaemia. Active BAT is present in adult humans and its activity is impaired in patients with obesity. The ability of BAT to protect against chronic metabolic disease has traditionally been attributed to its capacity to utilize glucose and lipids for thermogenesis. However, BAT might also have a secretory role, which could contribute to the systemic consequences of BAT activity. Several BAT-derived molecules that act in a paracrine or autocrine manner have been identified. Most of these factors promote hypertrophy and hyperplasia of BAT, vascularization, innervation and blood flow, processes that are all associated with BAT recruitment when thermogenic activity is enhanced. Additionally, BAT can release regulatory molecules that act on other tissues and organs. This secretory capacity of BAT is thought to be involved in the beneficial effects of BAT transplantation in rodents. Fibroblast growth factor 21, IL-6 and neuregulin 4 are among the first BAT-derived endocrine factors to be identified. In this Review, we discuss the current understanding of the regulatory molecules (the so-called brown adipokines or batokines) that are released by BAT that influence systemic metabolism and convey the beneficial metabolic effects of BAT activation. The identification of such adipokines might also direct drug discovery approaches for managing obesity and its associated chronic metabolic diseases.

                Author and article information

                Journal
                Endocr Connect
                Endocr Connect
                EC
                Endocrine Connections
                Bioscientifica Ltd (Bristol )
                2049-3614
                18 June 2024
                23 May 2024
                01 July 2024
                : 13
                : 7
                : e240074
                Affiliations
                [1 ]Division of Endocrinology , Department of Medicine, Leiden University Medical Center, Leiden, The Netherlands
                [2 ]Einthoven Laboratory for Experimental Vascular Medicine , Leiden University Medical Center, Leiden, The Netherlands
                [3 ]Department of Nursing Physiotherapy and Medicine , SPORT Research Group (CTS-1024), CERNEP Research Center, University of Almería, Almería, Spain
                [4 ]Biomedical Research Unit , Torrecárdenas University Hospital, Almería, Spain
                [5 ]CIBER de Fisiopatología de la Obesidad y Nutrición (CIBEROBN) , Instituto de Salud Carlos III, Granada, Spain
                [6 ]Bioscience Metabolism , Research and Early Development, Cardiovascular, Renal and Metabolism (CVRM), BioPharmaceuticals R&D, AstraZeneca Gothenburg, Sweden
                [7 ]Department of Medicine , Huddinge, Karolinska Institutet Campus Flemingsberg, Neo Building, Huddinge, Sweden
                [8 ]Laboratory of Experimental Cardiology , University Medical Center Utrecht, Utrecht, The Netherlands
                Author notes
                Correspondence should be addressed to C Hoekx: c.a.hoekx@ 123456lumc.nl

                *(C A Hoekx and B Martinez-Tellez contributed equally to the article and share first authorship)

                †(P C N Rensen and M R Boon share senior authorship)

                Author information
                http://orcid.org/0000-0001-6941-7339
                Article
                EC-24-0074
                10.1530/EC-24-0074
                11227058
                38781402
                2eb05312-2ef5-4141-bba8-b2d454c52cf8
                © the author(s)

                This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

                History
                : 21 February 2024
                : 23 May 2024
                Funding
                Funded by: Ministerio de Universidades, doi http://dx.doi.org/10.13039/501100023561;
                Funded by: Heart Foundation, doi http://dx.doi.org/10.13039/100002129;
                Funded by: Heart Foundation, doi http://dx.doi.org/10.13039/100002129;
                Funded by: Heart Foundation, doi http://dx.doi.org/10.13039/100002129;
                Categories
                Research
                EC-Obesity, Obesity
                Custom metadata
                EC-Obesity

                circadian rhythm,energy metabolism,cold stimulus,brown adipose tissue

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