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Cell Reports. Medicine Oct 2021The Scandinavian winter-swimming culture combines brief dips in cold water with hot sauna sessions, with conceivable effects on body temperature. We study thermogenic...
The Scandinavian winter-swimming culture combines brief dips in cold water with hot sauna sessions, with conceivable effects on body temperature. We study thermogenic brown adipose tissue (BAT) in experienced winter-swimming men performing this activity 2-3 times per week. Our data suggest a lower thermal comfort state in the winter swimmers compared with controls, with a lower core temperature and absence of BAT activity. In response to cold, we observe greater increases in cold-induced thermogenesis and supraclavicular skin temperature in the winter swimmers, whereas BAT glucose uptake and muscle activity increase similarly to those of the controls. All subjects demonstrate nocturnal reduction in supraclavicular skin temperature, whereas a distinct peak occurs at 4:30-5:30 a.m. in the winter swimmers. Our data leverage understanding of BAT in adult human thermoregulation, suggest both heat and cold acclimation in winter swimmers, and propose winter swimming as a potential strategy for increasing energy expenditure.
Topics: Adipose Tissue, Brown; Adult; Circadian Rhythm; Cold Temperature; Hormones; Humans; Magnetic Resonance Imaging; Male; Perception; Positron-Emission Tomography; Seasons; Skin Temperature; Swimming; Thermogenesis; Thermography; Young Adult
PubMed: 34755128
DOI: 10.1016/j.xcrm.2021.100408 -
Nature Reviews. Molecular Cell Biology Nov 2016Brown and beige adipocytes expend chemical energy to produce heat and are therefore important in regulating body temperature and body weight. Brown adipocytes develop in... (Review)
Review
Brown and beige adipocytes expend chemical energy to produce heat and are therefore important in regulating body temperature and body weight. Brown adipocytes develop in discrete and relatively homogenous depots of brown adipose tissue, whereas beige adipocytes are induced to develop in white adipose tissue in response to certain stimuli - notably, exposure to cold. Fate-mapping analyses have identified progenitor populations that give rise to brown and beige fat cells, and have revealed unanticipated cell-lineage relationships between vascular smooth muscle cells and beige adipocytes, and between skeletal muscle cells and brown fat. In addition, non-adipocyte cells in adipose tissue, including neurons, blood vessel-associated cells and immune cells, have crucial roles in regulating the differentiation and function of brown and beige fat.
Topics: Adipocytes; Adipose Tissue, Beige; Adipose Tissue, Brown; Animals; Cell Communication; Cell Differentiation; Energy Metabolism; Humans; Obesity; Thermogenesis
PubMed: 27552974
DOI: 10.1038/nrm.2016.96 -
Handbook of Experimental Pharmacology 2019Brown adipose tissue is well known to be a thermoregulatory organ particularly important in small rodents and human infants, but it was only recently that its existence... (Review)
Review
Brown adipose tissue is well known to be a thermoregulatory organ particularly important in small rodents and human infants, but it was only recently that its existence and significance to metabolic fitness in adult humans have been widely realized. The ability of active brown fat to expend high amounts of energy has raised interest in stimulating thermogenesis therapeutically to treat metabolic diseases related to obesity and type 2 diabetes. In parallel, there has been a surge of research aimed at understanding the biology of rodent and human brown fat development, its remarkable metabolic properties, and the phenomenon of white fat browning, in which white adipocytes can be converted into brown like adipocytes with similar thermogenic properties. Here, we review the current understanding of the developmental and metabolic pathways involved in forming thermogenic adipocytes, and highlight some of the many unknown functions of brown fat that make its study a rich and exciting area for future research.
Topics: Adipogenesis; Adipose Tissue, Brown; Adipose Tissue, White; Adult; Diabetes Mellitus, Type 2; Energy Metabolism; Humans; Thermogenesis
PubMed: 30203328
DOI: 10.1007/164_2018_168 -
Hormone Molecular Biology and Clinical... Jul 2014The growing understanding of adipose tissue as an important endocrine organ with multiple metabolic functions has directed the attention to the (patho)physiology of... (Review)
Review
The growing understanding of adipose tissue as an important endocrine organ with multiple metabolic functions has directed the attention to the (patho)physiology of distinct fat depots. Brown adipose tissue (BAT), in contrast to bona fide white fat, can dissipate significant amounts of chemical energy through uncoupled respiration and heat production (thermogenesis). This process is mediated by the major thermogenic factor uncoupling protein-1 and can be activated by certain stimuli, such as cold exposure, adrenergic compounds or genetic alterations. White adipose tissue (WAT) depots, however, also possess the capacity to acquire brown fat characteristics in response to thermogenic stimuli. The induction of a BAT-like cellular and molecular program in WAT has recently been termed "browning" or "beiging". Promotion of BAT activity or the browning of WAT is associated with in vivo cold tolerance, increased energy expenditure, and protection against obesity and type 2 diabetes. These preclinical observations have gained additional significance with the recent discovery that active BAT is present in adult humans and can be detected by 18fluor-deoxy-glucose positron emission tomography coupled with computed tomography. As in rodents, human BAT can be activated by cold exposure and is associated with increased energy turnover and lower body fat mass. Despite the tremendous progress in brown fat research in recent years, pharmacological concepts to harness BAT function therapeutically are currently still lacking.
Topics: Adipocytes; Adipose Tissue, Brown; Adipose Tissue, White; Animals; Diabetes Mellitus, Type 2; Energy Metabolism; Humans; Ion Channels; Mitochondrial Proteins; Obesity; Thermogenesis; Transcription, Genetic; Uncoupling Protein 1
PubMed: 25390014
DOI: 10.1515/hmbci-2014-0022 -
Nature Aug 2019Branched-chain amino acid (BCAA; valine, leucine and isoleucine) supplementation is often beneficial to energy expenditure; however, increased circulating levels of...
Branched-chain amino acid (BCAA; valine, leucine and isoleucine) supplementation is often beneficial to energy expenditure; however, increased circulating levels of BCAA are linked to obesity and diabetes. The mechanisms of this paradox remain unclear. Here we report that, on cold exposure, brown adipose tissue (BAT) actively utilizes BCAA in the mitochondria for thermogenesis and promotes systemic BCAA clearance in mice and humans. In turn, a BAT-specific defect in BCAA catabolism attenuates systemic BCAA clearance, BAT fuel oxidation and thermogenesis, leading to diet-induced obesity and glucose intolerance. Mechanistically, active BCAA catabolism in BAT is mediated by SLC25A44, which transports BCAAs into mitochondria. Our results suggest that BAT serves as a key metabolic filter that controls BCAA clearance via SLC25A44, thereby contributing to the improvement of metabolic health.
Topics: Adipose Tissue, Brown; Amino Acid Transport Systems; Amino Acids, Branched-Chain; Animals; Cold Temperature; Energy Metabolism; Glucose Intolerance; Homeostasis; Humans; Male; Mice; Mitochondria; Mitochondrial Proteins; Obesity; Solute Carrier Proteins; Thermogenesis
PubMed: 31435015
DOI: 10.1038/s41586-019-1503-x -
Journal of Internal Medicine Nov 2018Many of the comorbidities of obesity, including type 2 diabetes and cardiovascular diseases, are related to the low-grade chronic inflammation of white adipose tissue.... (Review)
Review
Many of the comorbidities of obesity, including type 2 diabetes and cardiovascular diseases, are related to the low-grade chronic inflammation of white adipose tissue. Under white adipocyte stress, local infiltration of immune cells and enhanced production of pro-inflammatory cytokines together reduce metabolic flexibility and lead to insulin resistance in obesity. Whereas white adipocytes act in energy storage, brown and beige adipocytes specialize in energy expenditure. Brown and beige activity protects against obesity and associated metabolic disorders, such as hyperglycaemia and hyperlipidaemia. Compared to white fat, brown adipose tissue depots are less susceptible to developing local inflammation in response to obesity; however, strong obesogenic insults ultimately induce a locally pro-inflammatory environment in brown fat. This condition directly alters the thermogenic activity of brown fat by impairing its energy expenditure mechanism and uptake of glucose for use as a fuel substrate. Pro-inflammatory cytokines also impair beige adipogenesis, which occurs mainly in subcutaneous adipose tissue. There is evidence that inflammatory processes occurring in perivascular adipose tissues alter their brown-versus-white plasticity, impair the extent of browning in these depots and favour the local release of vasculature damaging signals. In summary, the targeting of brown and beige adipose tissues by pro-inflammatory signals and the subsequent impairment of their thermogenic and metabolite draining activities appears to represent obesity-driven disturbances that contribute to metabolic syndrome and cardiovascular alterations in obesity.
Topics: Adipose Tissue, Beige; Adipose Tissue, Brown; Animals; Humans; Inflammation; Metabolic Diseases; Obesity
PubMed: 29923291
DOI: 10.1111/joim.12803 -
Nature Metabolism Apr 2021Brown adipose tissue can expend large amounts of energy, and therefore increasing its size or activity is a promising therapeutic approach to combat metabolic disease....
Brown adipose tissue can expend large amounts of energy, and therefore increasing its size or activity is a promising therapeutic approach to combat metabolic disease. In humans, major deposits of brown fat cells are found intimately associated with large blood vessels, corresponding to perivascular adipose tissue (PVAT). However, the cellular origins of PVAT are poorly understood. Here, we determine the identity of perivascular adipocyte progenitors in mice and humans. In mice, thoracic PVAT develops from a fibroblastic lineage, consisting of progenitor cells (Pdgfra, Ly6a and Pparg) and preadipocytes (Pdgfra, Ly6a and Pparg), which share transcriptional similarity with analogous cell types in white adipose tissue. Interestingly, the aortic adventitia of adult animals contains a population of adipogenic smooth muscle cells (Myh11, Pdgfra and Pparg) that contribute to perivascular adipocyte formation. Similarly, human PVAT contains presumptive fibroblastic and smooth muscle-like adipocyte progenitor cells, as revealed by single-nucleus RNA sequencing. Together, these studies define distinct populations of progenitor cells for thermogenic PVAT, providing a foundation for developing strategies to augment brown fat activity.
Topics: Adipocytes, Brown; Adipocytes, White; Adipogenesis; Adipose Tissue, Brown; Animals; Animals, Newborn; Aorta; Blood Vessels; Cell Lineage; Fibroblasts; Gene Expression Regulation; Humans; Infant, Newborn; Mice; Mice, Inbred C57BL; Myocytes, Smooth Muscle; Stem Cells; Thermogenesis
PubMed: 33846639
DOI: 10.1038/s42255-021-00380-0 -
Hormone Molecular Biology and Clinical... Jan 2017Beige or brite (brown-in-white) adipocytes are present in white adipose tissue (WAT) and have a white fat-like phenotype that when stimulated acquires a brown fat-like... (Review)
Review
Beige or brite (brown-in-white) adipocytes are present in white adipose tissue (WAT) and have a white fat-like phenotype that when stimulated acquires a brown fat-like phenotype, leading to increased thermogenesis. This phenomenon is known as browning and is more likely to occur in subcutaneous fat depots. Browning involves the expression of many transcription factors, such as PR domain containing 16 (PRDM16) and peroxisome proliferator-activated receptor (PPAR)-γ, and of uncoupling protein (UCP)-1, which is the hallmark of thermogenesis. Recent papers pointed that browning can occur in the WAT of humans, with beneficial metabolic effects. This fact indicates that these cells can be targeted to treat a range of diseases, with both pharmacological and nutritional activators. Pharmacological approaches to induce browning include the use of PPAR-α agonist, adrenergic receptor stimulation, thyroid hormone administration, irisin and FGF21 induction. Most of them act through the induction of PPAR-γ coactivator (PGC) 1-α and the consequent mitochondrial biogenesis and UCP1 induction. About the nutritional inducers, several compounds have been described with multiple mechanisms of action. Some of these activators include specific amino acids restriction, capsaicin, bile acids, Resveratrol, and retinoic acid. Besides that, some classes of lipids, as well as many plant extracts, have also been implicated in the browning of WAT. In conclusion, the discovery of browning in human WAT opens the possibility to target the adipose tissue to fight a range of diseases. Studies have arisen showing promising results and bringing new opportunities in thermogenesis and obesity control.
Topics: Adaptation, Biological; Adipocytes; Adipocytes, Beige; Adipose Tissue, Brown; Adipose Tissue, White; Animals; Cold Temperature; Energy Metabolism; Gene Expression Regulation; Humans; Models, Animal; Nutritional Physiological Phenomena; Signal Transduction; Thermogenesis
PubMed: 28099124
DOI: 10.1515/hmbci-2016-0051 -
Frontiers in Endocrinology 2020Since the recent rediscovery of brown adipose tissue (BAT) in adult humans, this thermogenic tissue has been attracting increasing interest. The inverse relationship... (Review)
Review
Since the recent rediscovery of brown adipose tissue (BAT) in adult humans, this thermogenic tissue has been attracting increasing interest. The inverse relationship between BAT activity and body fatness suggests that BAT, because of its energy dissipating activity, is protective against body fat accumulation. Cold exposure activates and recruits BAT, resulting in increased energy expenditure and decreased body fatness. The stimulatory effects of cold exposure are mediated through transient receptor potential (TRP) channels and the sympathetic nervous system (SNS). Most TRP members also function as chemesthetic receptors for various food ingredients, and indeed, agonists of TRP vanilloid 1 such as capsaicin and its analog capsinoids mimic the effects of cold exposure to decrease body fatness through the activation and recruitment of BAT. The antiobesity effect of other food ingredients including tea catechins may be attributable, at least in part, to the activation of the TRP-SNS-BAT axis. BAT is also involved in the facultative thermogenesis induced by meal intake, referred to as diet-induced thermogenesis (DIT), which is a significant component of the total energy expenditure in our daily lives. Emerging evidence suggests a crucial role for the SNS in BAT-associated DIT, particularly during the early phase, but several gut-derived humoral factors may also participate in meal-induced BAT activation. One intriguing factor is bile acids, which activate BAT directly through Takeda G-protein receptor 5 (TGR5) in brown adipocytes. Given the apparent beneficial effects of some TRP agonists and bile acids on whole-body substrate and energy metabolism, the TRP/TGR5-BAT axis represents a promising target for combating obesity and related metabolic disorders in humans.
Topics: Adipose Tissue, Brown; Animals; Diet; Energy Metabolism; Humans; Obesity; Thermogenesis
PubMed: 32373072
DOI: 10.3389/fendo.2020.00222 -
Cell Jul 2012Brown fat generates heat via the mitochondrial uncoupling protein UCP1, defending against hypothermia and obesity. Recent data suggest that there are two distinct types...
Brown fat generates heat via the mitochondrial uncoupling protein UCP1, defending against hypothermia and obesity. Recent data suggest that there are two distinct types of brown fat: classical brown fat derived from a myf-5 cellular lineage and UCP1-positive cells that emerge in white fat from a non-myf-5 lineage. Here, we report the isolation of "beige" cells from murine white fat depots. Beige cells resemble white fat cells in having extremely low basal expression of UCP1, but, like classical brown fat, they respond to cyclic AMP stimulation with high UCP1 expression and respiration rates. Beige cells have a gene expression pattern distinct from either white or brown fat and are preferentially sensitive to the polypeptide hormone irisin. Finally, we provide evidence that previously identified brown fat deposits in adult humans are composed of beige adipocytes. These data provide a foundation for studying this mammalian cell type with therapeutic potential. PAPERCLIP:
Topics: Adipocytes; Adipocytes, White; Adipose Tissue, Brown; Animals; Cell Separation; Gene Expression Profiling; Humans; Ion Channels; Mice; Mitochondrial Proteins; Uncoupling Protein 1
PubMed: 22796012
DOI: 10.1016/j.cell.2012.05.016