Human brown adipose tissue detected by fluorodeoxyglucose (FDG)-positron emission tomography (PET). FDG uptake into adipose tissue at the supraclavicular and paraspinal regions is detected by PET. The FDG uptake into adipose tissues is negligible under a warm condition at 27℃ (A), but increases greatly after exposure to cold at 19℃ (B) for 2 hours.

Human brown adipose tissue detected by fluorodeoxyglucose (FDG)-positron emission tomography (PET). FDG uptake into adipose tissue at the supraclavicular and paraspinal regions is detected by PET. The FDG uptake into adipose tissues is negligible under a warm condition at 27℃ (A), but increases greatly after exposure to cold at 19℃ (B) for 2 hours.

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Brown adipose tissue (BAT) is recognized as the major site of sympathetically activated nonshivering thermogenesis during cold exposure and after spontaneous hyperphagia, thereby controling whole-body energy expenditure and body fat. In adult humans, BAT has long been believed to be absent or negligible, but recent studies using fluorodeoxyglucose-...

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... Flattening of GC oscillations results in strong and rapid upregulation of de novo fatty acid synthesis genes in WAT and BAT We focused on vWAT since its expansion has been recognized to be detrimental to metabolic health, while expansion of sWAT may be protective (Ghaben and Scherer, 2019;Shao et al., 2018). We also analyzed BAT because of increasing evidence that BAT activity can significantly affect whole-body energy expenditure and fat tissue mass (Cannon and Nedergaard, 2004;Saito, 2013). We harvested vWAT and BAT between 1 and 5 p.m. at four time points: 0, 3, 7, and 14 days after pellet implantation and carried out RNA sequencing (RNA-seq) analysis. ...
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Disruption of circadian glucocorticoid oscillations in Cushing’s disease and chronic stress results in obesity and adipocyte hypertrophy, which is believed to be a main source of the harmful effects of obesity. Here, we recapitulate stress due to jet lag or work-life imbalances by flattening glucocorticoid oscillations in mice. Within 3 days, mice achieve a metabolic state with persistently high insulin, but surprisingly low glucose and fatty acids in the bloodstream, that precedes a more than 2-fold increase in brown and white adipose tissue mass within 3 weeks. Transcriptomic and Cd36-knockout mouse analyses show that hyperinsulinemia-mediated de novo fatty acid synthesis and Cd36-mediated fatty acid uptake drive fat mass increases. Intriguingly, this mechanism by which glucocorticoid flattening causes acute hyperinsulinemia and adipocyte hypertrophy is unexpectedly beneficial in preventing high levels of circulating fatty acids and glucose for weeks, thus serving as a protective response to preserve metabolic health during chronic stress.
... Furthermore, although mean glucose levels appeared similar (Supplemental Figure 2d), glucose telemetry monitoring revealed that glucose levels decreased during the inactive period and increased during the active period to a larger extent in KI rats compared to WT rats (Supplemental Figure 10). This suggests an increased turnover of glucose that may also contribute to thermogenesis as a carbon source for synthesis and rapid oxidation of fatty acids [29,30], which is consistent with the increase in the expression of genes involved in glycolysis and neoglucogenesis (Supplemental Figure 7C). Finally, a NMR-based metabolomic profiling approach performed on the serum of fasted rats showed a decrease in both glycine and betaine levels, suggesting an alteration of the 1-carbon metabolism pathway that could explain the slight growth defect in KI rats, but also decreased citrate levels illustrating alterations in TCA, and TCA-linked lipogenesis (Supplemental Table 2). ...
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Introduction Although the physiological role of the C-terminal hydrolase domain of the soluble epoxide hydrolase (sEH-H) is well investigated, the function of its N-terminal phosphatase activity (sEH-P) remains unknown. This study aimed to assess in vivo the physiological role of sEH-P. Methods CRISPR/Cas9 was used to generate a novel knock-in (KI) rat line lacking the sEH-P activity Results The sEH-P KI rats has a decreased metabolism of lysophosphatidic acids to monoacyglycerols. KI rats grew almost normally but with less weight and fat mass gain while insulin sensitivity was increased compared to wild-type rats. This lean phenotype was more marked in males than in female KI rats and mainly due to decreased food consumption and enhanced energy expenditure. In fact, sEH-P KI rats had an increased lipolysis allowing to supply fatty acids as fuel to potentiate brown adipose thermogenesis under resting condition and upon cold exposure. The potentiation of thermogenesis was abolished when blocking PPARγ, a nuclear receptor activated by intracellular lysophosphatidic acids, but also when inhibiting simultaneously sEH-H, showing a functional interaction between the two domains. Furthermore, sEH-P KI rats fed a high-fat diet did not gain as much weight as the wild-type rats, did not have increased fat mass and did not develop insulin resistance or hepatic steatosis. In addition, sEH-P KI rats exhibited enhanced basal cardiac mitochondrial activity associated with an enhanced left ventricular contractility and were protected against cardiac ischemia-reperfusion injury. Conclusion Our study reveals that sEH-P is a key player in energy and fat metabolism and contributes together with sEH-H to the regulation of cardiometabolic homeostasis. The development of pharmacological inhibitors of sEH-P appears of crucial importance to evaluate the interest of this promising therapeutic strategy in the management of obesity and cardiac ischemic complications.
... Brown adipose tissue (BAT) is a specialized site for uncoupling protein 1 (UCP1)mediated non-shivering thermogenesis [1]. BAT dissipates chemical energy via heat generation to maintain the optimal body temperature against cold exposure and increases energy expenditure in response to excessive feeding [2]. Recent technical advances in the field of energy metabolism have revealed that the thermogenesis in BAT uses large amounts of intracellular triglycerides and glucose as the energy source [3,4], and thus activating the thermogenesis of BAT is a promising target for the treatment of obesity and related diseases, such as diabetes, dyslipidemia, and cardiovascular diseases [1,5]. ...
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Brown adipose tissue (BAT) is a major site for uncoupling protein 1 (UCP1)-mediated non-shivering thermogenesis. BAT dissipates energy via heat generation to maintain the optimal body temperature and increases energy expenditure. These energetic processes in BAT use large amounts of glucose and fatty acid. Therefore, the thermogenesis of BAT may be harnessed to treat obesity and related diseases. In mice and humans, BAT levels decrease with aging, and the underlying mechanism is elusive. Here, we compared the transcriptomic profiles of both young and aged BAT in response to thermogenic stimuli. The profiles were extracted from the GEO database. Intriguingly, aging does not cause transcriptional changes in thermogenic genes but upregulates several pathways related to the immune response and downregulates metabolic pathways. Acute severe CE upregulates several pathways related to protein folding. Chronic mild CE upregulates metabolic pathways, especially related to carbohydrate metabolism. Our findings provide a better understanding of the effects of aging and metabolic responses to thermogenic stimuli in BAT at the transcriptome level.
... Brown adipose tissue (BAT) is the major site of nonshivering thermogenesis (NST) during cold exposure [cold-induced thermogenesis (CIT)] in small rodents [13]. Since the rediscovery of metabolically active BAT using [ 18 F]fluorodeoxyglucose positron emission tomography and computed tomography (FDG-PET/CT) in adult humans [14][15][16][17], it has been confirmed that human BAT is activated by cold exposure and contributes to the increase of whole-body EE and fatty acid oxidations, and thereby to the regulation of body fat [18][19][20]. Although cold exposure is undoubtedly the most physiological and effective regimen to activate and recruit BAT, increasing exposure to cold temperatures in our daily life would be difficult and uncomfortable. ...
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Background/objectives Disturbed circadian rhythm is associated with an increased risk of obesity and metabolic disorders. Brown adipose tissue (BAT) is a site of nonshivering thermogenesis (NST) and plays a role in regulating whole-body energy expenditure (EE), substrate metabolism, and body fatness. In this study, we examined diurnal variations of NST in healthy humans by focusing on their relation to BAT activity. Methods Forty-four healthy men underwent ¹⁸F-fluoro-2-deoxy-D-glucose positron emission tomography and were divided into Low-BAT and High-BAT groups. In STUDY 1, EE, diet-induced thermogenesis (DIT), and fat oxidation (FO) were measured using a whole-room indirect calorimeter at 27 °C. In STUDY 2, EE, FO, and skin temperature in the region close to BAT depots (Tscv) and in the control region (Tc) were measured at 27 °C and after 90 min cold exposure at 19 °C in the morning and in the evening. Results In STUDY 1, DIT and FO after breakfast was higher in the High-BAT group than in the Low-BAT group (P < 0.05), whereas those after dinner were comparable in the two groups. FO in the High-BAT group was higher after breakfast than after dinner (P < 0.01). In STUDY 2, cold-induced increases in EE (CIT), FO, and Tscv relative to Tc in the morning were higher in the High-BAT group than in the Low-BAT group (P < 0.05), whereas those after dinner were comparable in the two groups. CIT in the High-BAT group tended to be higher in the morning than in the evening (P = 0.056). Conclusion BAT-associated NST and FO were evident in the morning, but not in the evening, suggesting that the activity of human BAT is higher in the morning than in the evening, and thus may be involved in the association of an eating habit of breakfast skipping with obesity and related metabolic disorders.
... In contrast, brown adipose tissue (BAT) is responsible for non-shivering thermogenesis and heat production [1,2]. Importantly, BAT is involved in the reduction of plasma triglyceride and glucose levels, contributing to the alleviation of metabolic syndrome [3][4][5][6]. Beige adipocytes exist between brown and white adipocytes and are rich in mitochondria compared to WAT and inducible UCP1-positive adipocytes that are interspersed among white adipocytes in WAT [7,8]. Beige adipocytes are also regarded as a BAT subtype that plays important roles in energy homeostasis and thermogenesis [9,10]. ...
... Unlike WAT, BAT is known to play a critical role in energy homeostasis and thermogenesis in mammals, thereby protecting against diet-induced metabolic syndrome and hypothermia via the action of uncoupling protein 1 (UCP1) [3][4][5][6]. UCP1 is a unique mitochondrial protein that uncouples the electron transfer system from ATP synthesis in the mitochondria, which in turn consumes energy as heat [4,5,24]. Similarly, the expression of PGC−1α, which is a master regulator of mitochondrial biogenesis, was also increased during BAT development [14,15]. ...
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Brown adipose tissue (BAT) plays an important role in thermogenic regulation, which contributes to alleviating diet-induced obesity through uncoupling protein 1 (UCP1) expression. While cold exposure and physical exercise are known to increase BAT development and UCP1 expression, the contribution of hyperbaric oxygen (HBO) therapy to BAT maturation remains largely unknown. Here, we show that HBO treatment sufficiently increases BAT volumes and thermogenic protein levels in Sprague-Dawley rats. Through 18F-FDG PET/CT analysis, we found that exposure to high-pressure oxygen (1.5–2.5 ATA) for 7 consecutive days increased radiolabeled glucose uptake and BAT development to an extent comparable to cold exposure. Consistent with BAT maturation, thermogenic protein levels, such as those of UCP1 and peroxisome proliferator-activated receptor γ coactivator 1α (PGC−1α), were largely increased by HBO treatment. Taken together, we suggest HBO therapy as a novel method of inducing BAT development, considering its therapeutic potential for the treatment of metabolic disorders.
... Perhaps the most serious gap in our understanding of the age-associated metabolic decline of trauma patients is the role of the adipose tissue, in particular how adipose tissue remodeling from white-to brown-like adipocytes affects energy expenditure and outcomes (10)(11)(12). Whereas white adipose tissue (WAT) is responsible for storing large amounts of triglycerides, brown adipose tissue (BAT) is characterized by smaller lipid droplets, increased mitochondrial biogenesis, and the expression of uncoupling protein 1 (UCP1), which uncouples ATP generation from oxidative phosphorylation, thus dissipating energy as heat (13)(14)(15). Unfortunately, both BAT activity and quantity have been shown to decline during aging, with diminished reserves occurring as early as the mid-40s in humans and in midlife for rodents (11). ...
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BACKGROUND The incidence of burn injuries in older patients is dramatically increasing as the population of older people grows. Despite the increased demand for elderly burn care, the mechanisms that mediate increased morbidity and mortality in older trauma patients are unknown. We recently showed that a burn injury invokes white adipose tissue browning that leads to a substantially increased hypermetabolic response associated with poor outcomes. Therefore, the aim of this study was to determine the effect of age on the metabolic adipose response of browning after a burn injury.METHOD One hundred and seventy patients with burn injury admitted to the Ross Tilley Burn Centre were prospectively enrolled and grouped by age as older (≥50 years) and young (≤35 years). Adipose tissue and sera were collected and analyzed for browning markers and metabolic state via histology, gene expression, and resting energy expenditure assays.RESULTSWe found that older patients with burn injury lacked the adipose browning response, as they showed significant reductions in uncoupling protein 1 (UCP1) expression. This failure of the browning response was associated with reduced whole-body metabolism and decreased survival in older patients with burn injury. Mechanistically, we found that the adipose of both aged patients after burn trauma and aged mice after a burn showed impairments in macrophage infiltration and IL-6, key immunological regulators of the browning process after a severe trauma.CONCLUSION Targeting pathways that activate the browning response represents a potential therapeutic approach to improve outcomes after burn trauma for elderly patients.FUNDINGNIH (R01-GM087285-01), Canadian Institutes of Health Research (grant no. 123336), and Canada Foundation for Innovation Leaders Opportunity Fund (no. 25407).
... The sympathetic activation leads to mobilization of fatty acids from WAT, which are then utilized by BAT to dissipate energy as heat [31]. Especially, systemic ADRB3 activation in rodents enhances thermogenic capacity of both brown and beige adipocytes, and it is accompanied by the secretion of catecholamine [2,32]. ...
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Background/Objectives Translationally controlled tumor protein (TCTP) exhibits numerous biological functions. It has been shown to be involved in the regulation of glucose. However, its specific role in metabolism has not yet been clearly elucidated. Here, we aimed to assess the effect of TCTP overexpression on metabolic tissues and systemic energy metabolism. Subjects/Methods We investigated whether TCTP can ameliorate the metabolic imbalance that causes obesity using TCTP-overexpressing transgenic (TCTP TG) mice. The mice were subjected to biochemical, morphological, physiological and protein expression studies to define the role of TCTP in metabolic regulation in response to normal chow diet (NCD) compared to high-fat diet (HFD) conditions, and cold environment. Results We found that TCTP TG mice show improved metabolic homeostasis under both of NCD and HFD conditions with simultaneous enhancements in glucose tolerance and insulin sensitivity. In particular, we found coincident increases in energy expenditure with significant upregulation of uncoupling protein 1 (UCP1) in the brown adipose tissue (BAT). Moreover, TCTP overexpressing mice exhibit significantly enhanced adaptive thermogenesis of BAT in response to cold exposure. Conclusions Overexpression of TCTP ameliorated systemic metabolic homeostasis by stimulating UCP1-mediated thermogenesis in the BAT. This suggests that TCTP may function as a modulator of energy expenditure. This study suggests TCTP may serve as a therapeutic target for obesity and obesity-associated metabolic disorders including type 2 diabetes.
... Mammals have two types of adipose tissue, the white adipose tissue (WAT) and brown adipose tissue (BAT), which have opposite physiological roles: WAT is the site to store energy as triglyceride (TG), whereas BAT is a specialized tissue for nonshivering thermogenesis (NST) to dissipate energy as heat [1]. Although BAT research has long been limited mostly to small rodents, the rediscovery of metabolically active BAT using radionuclide imaging technique in adult humans [2][3][4][5] has dramatically accelerated the translational studies on BAT in health and diseases, particularly on its role in the regulation of energy balance, body fatness, and substrate metabolism [6,7]. Over the past decade, several remarkable advancements have been made in the field of brown fat biology. ...
... In adult humans, BAT is usually assessed by cold-activated glucose utilization using 18 F-fluorodeoxyglucose (FDG)-positron emission tomography (PET) [2][3][4][5][6]; that is, when FDG-PET is performed after either cold exposure or β3-AR agonist administration, it detects symmetrical FDG uptake in adipose tissue at the supraclavicular and thoracic spine regions. Histological examinations revealed the presence of UCP1-positive adipocytes surrounded by numerous UCP1-negative white adipocytes in these regions. ...
Article
Brown adipose tissue (BAT) is a specialized tissue for nonshivering thermogenesis to dissipate energy as heat. Although BAT research has long been limited mostly in small rodents, the rediscovery of metabolically active BAT in adult humans has dramatically promoted the translational studies on BAT in health and diseases. Moreover, several remarkable advancements have been made in brown fat biology over the past decade: The molecular and functional analyses of inducible thermogenic adipocytes (socalled beige adipocytes) arising from a developmentally different lineage from classical brown adipocytes have been accelerated. In addition to a well-established thermogenic activity of uncoupling protein 1 (UCP1), several alternative thermogenic mechanisms have been discovered, particularly in beige adipocytes. It has become clear that BAT influences other peripheral tissues and controls their functions and systemic homeostasis of energy and metabolic substrates, suggesting BAT as a metabolic regulator, other than for thermogenesis. This notion is supported by discovering that various paracrine and endocrine factors are secreted from BAT. We review the current understanding of BAT pathophysiology, particularly focusing on its role as a metabolic regulator in small rodents and also in humans.
... BAT is crucial for maintaining body temperature especially for infants who have limited ability to perform shivering thermogenesis, due to underdeveloped skeletal muscle (2). In adults, BAT contributes to energy expenditure as indicated by an inverse correlation between the presence of active BAT and central obesity (3,4). In addition to numerous mitochondria, BAT possesses multilocular lipid droplets that provide FAs for b-oxidation, which drives tricarboxylic acid (TCA) cycle and electron transport chain (ETC) to create proton gradient (5). ...
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Obesity, an excess accumulation of white adipose tissue (WAT), has become a global epidemic and is associated with complex diseases, such as type 2 diabetes and cardiovascular diseases. Presently, there are no safe and effective therapeutic agents to treat obesity. In contrast to white adipocytes that store energy as triglycerides in unilocular lipid droplet, brown and brown-like or beige adipocytes utilize fatty acids (FAs) and glucose at a high rate mainly by uncoupling protein 1 (UCP1) action to uncouple mitochondrial proton gradient from ATP synthesis, dissipating energy as heat. Recent studies on the presence of brown or brown-like adipocytes in adult humans have revealed their potential as therapeutic targets in combating obesity. Classically, the main signaling pathway known to activate thermogenesis in adipocytes is β 3 -adrenergic signaling, which is activated by norepinephrine in response to cold, leading to activation of the thermogenic program and browning. In addition to the β 3 -adrenergic signaling, numerous other hormones and secreted factors have been reported to affect thermogenesis. In this review, we discuss several major pathways, β 3 -adrenergic, insulin/IGF1, thyroid hormone and TGFβ family, which regulate thermogenesis and browning of WAT.
... BAT is a fat tissue that regulates energy balance and maintains core body temperature through sympathetic NST [1,35]. Insufficient BAT activity could lead to an energy imbalance, resulting in metabolic diseases like obesity and diabetes. ...
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Background Brown adipose tissue (BAT) is a fat tissue found in most mammals that helps regulate energy balance and core body temperature through a sympathetic process known as non-shivering thermogenesis. BAT activity is commonly detected and quantified in [¹⁸F]FDG positron emission tomography/computed tomography (PET/CT) scans, and radiotracer uptake in BAT during adrenergic stimulation is often used as a surrogate measure for identifying thermogenic activity in the tissue. BAT thermogenesis is believed to be contingent upon the expression of the protein UCP1, but conflicting results have been reported in the literature concerning [¹⁸F]FDG uptake within BAT of mice with and without UCP1. Differences in animal handling techniques such as feeding status, type of anesthetic, type of BAT stimulation, and estrogen levels were identified as possible confounding variables for [¹⁸F]FDG uptake. In this study, we aimed to assess differences in BAT [¹⁸F]FDG uptake between wild-type and UCP1-knockout mice using a protocol that minimizes possible variations in BAT stimulation caused by different stress responses to mouse handling. Results [¹⁸F]FDG PET/CT scans were run on mice that were anesthetized with pentobarbital after stimulation of non-shivering thermogenesis by norepinephrine. While in wild-type mice [¹⁸F]FDG uptake in BAT increased significantly with norepinephrine stimulation of BAT, there was no consistent change in [¹⁸F]FDG uptake in BAT of mice lacking UCP1. Conclusions [¹⁸F]FDG uptake within adrenergically stimulated BAT of wild-type and UCP1-knockout mice can significantly vary such that an [¹⁸F]FDG uptake threshold cannot be used to differentiate wild-type from UCP1-knockout mice. However, while an increase in BAT [¹⁸F]FDG uptake during adrenergic stimulation is consistently observed in wild-type mice, in UCP1-knockout mice [¹⁸F]FDG uptake in BAT seems to be independent of β3-adrenergic stimulation of non-shivering thermogenesis.