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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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Citations
... In adult humans, thermogenic brown adipose tissue (BAT) is localized to the supraclavicular, axillary, and mediastinal regions of the body. Studies have shown that activation of brown fat NST using mild environmental cold exposure periods is associated with enhanced whole-body metabolism such as increased resting metabolic rates, improved lipid and glucose profiles, and increased insulin tolerance [10][11][12][13]. While there have been significant advances in the mechanisms that govern the NST activation process such as Nutrients 2023, 15, 3532 2 of 18 cold environmental stimuli or the administration of pharmacological agents such as the β 3 agonist CL 316,243, practical and safe approaches to stimulate NST in humans are still challenging [14,15]. ...
Non-shivering thermogenesis (NST) has strong potential to combat obesity; however, a safe molecular approach to activate this process has not yet been identified. The sulfur amino acid taurine has the ability to safely activate NST and confer protection against obesity and metabolic disease in both mice and humans, but the mechanism of this action is unknown. In this study, we discover that a suite of taurine biosynthetic enzymes, especially that of cysteamine dioxygenase (ADO), significantly increases in response to β3 adrenergic signaling in inguinal adipose tissue (IWAT) in order to increase intracellular concentrations of taurine. We further show that ADO is critical for thermogenic mitochondrial respiratory function as its ablation in adipocytes significantly reduces taurine levels, which leads to declines in mitochondrial oxygen consumption rates. Finally, we demonstrate via assay for transposase-accessible chromatin with sequencing (ATAC-seq) that taurine supplementation in beige adipocytes has the ability to remodel the chromatin landscape to increase the chromatin accessibility and transcription of genes, such as glucose-6-phosphate isomerase 1 (Gpi1), which are critical for NST. Taken together, our studies highlight a potential mechanism for taurine in the activation of NST that can be leveraged toward the treatment of obesity and metabolic disease.
... However, our indirect calorimetry results suggest that the decreased body weight induced by LPD feeding could be due to increased EE and fat/lean mass loss in adaptation to amino acid restriction, but not reduced food intake. In line with this hypothesis and other previous reports 50, 51 , LPD feeding in WT and IR FKO mice strongly actives the BAT thermogenesis, a critical contributor to adaptive energy expenditure [52][53][54] . Nevertheless, we are aware that our current energy expenditure data might not be able to address the metabolic state of the animals at the steady state under protein deprivation condition. ...
Long-term ad libitum dietary restrictions, such as low-protein diets (LPDs), improve metabolic health and extend the life span of mice and humans. However, most studies conducted thus far have focused on the preventive effects of LPDs on metabolic syndromes. To test the therapeutic potential of LPD, we treated a lipodystrophy mouse model IRFKO (adipose-specific insulin receptor knockout) in this study. We have previously shown that IRFKO mice have profound insulin resistance, hyperglycemia, and whitening of interscapular brown adipose tissue (BAT), closely mimicking the phenotypes in lipoatrophic diabetic patients. Here, we demonstrate that 14-day of LPD (5.1% kcal from protein) feeding is sufficient to reduce postprandial blood glucose, improve insulin resistance, and normalize glucose tolerance in the IRFKO mice. This profound metabolic improvement is associated with BAT activation and increase in whole body energy expenditure. To confirm, we showed that surgical denervation of BAT attenuated the beneficial metabolic effects of LPD feeding in IRFKO mice, including the ‘browning’ effects on BAT and the glucose-ameliorating results. However, BAT denervation failed to affect the body weight-lowering effects of LPD. Together, our results imply a therapeutic potential to use LPD for the treatment of lipoatrophic diabetes.
... When the room temperature was gradually lowered from 26.5 to 20 °C, young subjects kept their CBT unchanged, while older subjects could not keep their CBT and it gradually decreased 17 . The deteriorated adaptation ability and reduced capacity for brown fat thermogenesis 18 would make the CBT of older subjects easily affected by lower environmental temperature. The second study is about the timing of the batiphase of CBT. ...
Core body temperature (CBT) shows a diurnal rhythm, and the nocturnal decrease in CBT is blunted in older people. The physiological mechanisms responsible for the blunted nocturnal decrease in CBT in older people remain to be revealed. The aim of this study was to compare heat production and heat dissipation in young and old subjects during sleep, as assessed by indirect calorimetry and the distal–proximal temperature gradient (DPG) of skin temperature. A complete dataset of 9 young (23.3 ± 1.1 years) and 8 old (72.1 ± 2.5 years) females was analyzed. CBT and energy metabolism were monitored during sleep using an ingestible temperature sensor in a metabolic chamber maintained at 25 °C. Skin temperature was measured at proximal and distal parts of the body. CBT, distal skin temperature, and DPG in older subjects were higher than in young subjects. Protein oxidation was similar between the two groups, but fat oxidation was lower and carbohydrate oxidation was higher in old subjects compared to young subjects. On the other hand, energy expenditure was similar between the two age groups. Thus, the elevated CBT in older subjects was not attributed to deteriorated heat dissipation or enhanced heat production, suggesting an alternative explanation such as deteriorated evaporative heat loss in old subjects.
... Nevertheless, our indirect calorimetry results suggest that the decreased body weight induced by LPD feeding is primarily due to increased EE but not reduced food intake. In line with this hypothesis and other previous reports 50, 51 , LPD feeding in WT and IR FKO mice strongly actives the BAT thermogenesis, a critical contributor to adaptive energy expenditure [52][53][54] . ...
Long-term ad libitum dietary restrictions, such as low-protein diets (LPDs), improve metabolic health and extend the life span of mice and humans. However, most studies conducted thus far have focused on the preventive effects of LPDs on metabolic syndromes. To test the therapeutic potential of LPD, we treated a lipodystrophy mouse model IR FKO (adipose-specific insulin receptor knockout) in this study. We have previously shown that IR FKO mice have profound insulin resistance, hyperglycemia, and whitenng of interscapular brown adipose tissue (BAT), closely mimicking the phenotypes in lipoatrophic diabetic patients. Here, we demonstrate that 14-day of LPD (5.1% kcal from protein) feeding is sufficient to reduce postprandial blood glucose, improve insulin resistance, and normalize glucose tolerance in the IR FKO mice. This profound metabolic improvement is associated with BAT activation and increase in whole body energy expenditure. To confirm, we showed that surgical denervation of BAT attenuated the beneficial metabolic effects of LPD feeding in IR FKO mice, including the ‘browning’ effects on BAT and the glucose-ameliorating results. However, BAT denervation failed to affect the body weight-lowering effects of LPD. Together, our results imply a therapeutic potential to use LPD for the treatment of lipoatrophic diabetes.
... Si le frisson ne suffit pas, d'autres mécanismes peuvent être stimulés par le froid afin d'agir sur la thermogénèse, notamment via l'activation du tissu adipeux brun (TAB). Le TAB est un organe thermogénique dont l'activation permet d'augmenter la production de chaleur en réponse à un stimulus froid afin de maintenir la température corporelle sans avoir recours au frisson (Kulterer et al., 2020a;Saito, 2013). S'il a longtemps été pensé que le TAB était spécifique aux petits mammifères et nouveau-nés, de nouvelles évidences ont démontré sa présence chez l'adulte et son implication dans la régulation de la thermogénèse et de la dépense énergétique totale journalière (DETJ) (Nedergaard et al., 2007). ...
... Celle-ci va se fixer sur les récepteurs β-adrénergiques et initier une cascade de réaction résultant en l'hydrolyse des triglycérides stockés dans le TAB. Les acides gras relâchés vont ainsi être oxydé pour produire de l'énergie qui sera dissipée sous forme de chaleur (Saito, 2013 3.8°C sans changement de la température interne après une exposition de 3h en milieu froid (≈18°C de façon à ne pas induire de frisson thermique) . ...
FRA:
La conquête de nouveaux horizons étant le propre l’humanité, elle a imposé aux individus de repousser leurs limites en s’acclimatant aux contraintes de l’environnement, jusqu’à certaines limites. La nutrition inadaptée aux besoins énergétiques en condition extrême est une de ces limites et impose aux participants de considérer la régulation de la balance énergétique comme une priorité. Cette thèse a pour objectif de quantifier objectivement les besoins énergétiques des individus en conditions environnementales extrêmes, ainsi que les changements de composition corporelle associés. Si la régulation de cette balance s’adapte aux perturbations légères grâce à la mise en place de mécanismes compensatoires, les résultats des modèles extrêmes utilisé dans ce travail de thèse montrent les limites de cette régulation en dehors d’un certain niveau d’activité physique dues à un découplage entre les apports et les dépenses énergétiques. Or, la capacité à maintenir une balance énergétique négative sur le long terme reste méconnue en raison de la nature diverse des compensations pouvant être stimulées, de la nature du déficit ou encore des caractéristiques individuelles des participants.
ENG:
The conquest of new horizons being the own of humanity, it compelled to individuals to push away their limits by acclimatize to the constraints of the environment, at least until certain limits. The mismatch between nutrition and energy requirements in extreme environment is one of these limits, and compels individuals to consider energy balance regulation as a priority. This thesis aims to objectively quantify individuals’ energy requirements in extreme conditions, and the associated body composition changes. While the regulation of energy balance is effective to face light disturbances on one component or another because of compensatory mechanisms, results from extreme models used in the present thesis show the limits of this regulation outside a certain range of physical activity level, mostly because of a mismatch between energy intakes and expenditures. However, the capacity to sustain a negative energy balance during prolonged period is poorly known, partly because of the broad range of compensatory mechanisms at play, but also the nature of the deficit or individuals’ characteristics.
... This observation was combined with a lower iBAT glucose uptake capacity of the p27 −/− HFD in response to acute cold exposure. These facts suggest that the impairment of iBAT observed in p27 −/− mice could affect whole-body oxygen consumption [50], favouring increased body fatness and impaired insulin sensitivity and glucose metabolism. Indeed, a less active BAT is linked to a higher susceptibility to develop obesity and insulin resistance, and studies propose BAT activation as a strategy to fight these diseases [24]. ...
The aim of this work was to investigate the effect of the whole-body deletion of p27 on the activity of brown adipose tissue and the susceptibility to develop obesity and glucose homeostasis disturbances in mice, especially when subjected to a high fat diet. p27 knockout (p27−/−) and wild type (WT) mice were fed a normal chow diet or a high fat diet (HFD) for 10-weeks. Body weight and composition were assessed. Insulin and glucose tolerance tests and indirect calorimetry assays were performed. Histological analysis of interscapular BAT (iBAT) was carried out, and expression of key genes/proteins involved in BAT function were characterized by qPCR and Western blot. iBAT activity was estimated by 18F-fluorodeoxyglucose (18FDG) uptake with microPET. p27−/− mice were more prone to develop obesity and insulin resistance, exhibiting increased size of all fat depots. p27−/− mice displayed a higher respiratory exchange ratio. iBAT presented larger adipocytes in p27−/− HFD mice, accompanied by downregulation of both Glut1 and uncoupling protein 1 (UCP1) in parallel with defective insulin signalling. Moreover, p27−/− HFD mice exhibited impaired response to cold exposure, characterized by a reduced iBAT 18FDG uptake and difficulty to maintain body temperature when exposed to cold compared to WT HFD mice, suggesting reduced thermogenic capacity. These data suggest that p27 could play a role in BAT activation and in the susceptibility to develop obesity and insulin resistance.
... Although BAT research has long been limited mostly in small rodents, the rediscovery of metabolically active BAT using fluorodeoxyglucose (FDG)-positron emission tomography (PET) and computed tomography (CT) in adult humans [1][2][3][4] has dramatically accelerated the translational studies on BAT in health and diseases. It is now established that BAT, through its thermogenic and energy dissipating activities, plays a role in the regulation of body temperature, energy expenditure (EE), and body fatness [5,6]. Moreover, over a past decade, increasing evidence has demonstrated that BAT cross talks with some peripheral tissues and controls their functions, systemic homeostasis of energy and metabolic substrates, suggesting BAT as a metabolic regulator beyond thermogenesis [7][8][9]. ...
In mammals including humans, there are two types of adipose tissue, white and brown adipose tissues (BATs). White adipose
tissue is the primary site of energy storage, while BAT is a specialized tissue for non-shivering 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. It is now established
that BAT, through its thermogenic and energy dissipating activities, plays a role in the regulation of body temperature, wholebody
energy expenditure, and body fatness. Moreover, increasing evidence has demonstrated that BAT secretes various paracrine
and endocrine factors, which influence other peripheral tissues and control systemic metabolic homeostasis, suggesting
BAT as a metabolic regulator, other than for thermogenesis. In fact, clinical studies have revealed an association of BAT not
only with metabolic disorders such as insulin resistance, diabetes, dyslipidemia, and fatty liver, but also with cardiovascular
diseases including hypertension and atherosclerosis. Thus, BAT is an intriguing tissue combating obesity and related metabolic
diseases. In this review, we summarize current knowledge on human BAT, focusing its patho-physiological roles in energy
homeostasis, obesity and related metabolic disorders. The effects of aging and sex on BAT are also discussed.
... A subset of adipose tissue termed brown adipose tissue possesses a diet-induced thermogenic activity [31], this process is performed as a compensatory mechanism for the increased food intake to increase energy expenditure exceeding the basal metabolic levels [32]. ...
Polycystic ovary syndrome (PCOS) is a pathological condition prevalent among women of reproductive age: it is associated with varied etiological factors (lifestyle, genetic, environmental…) and characterized by an increased polycystic morphology of the ovaries leading to disturbances in the menstrual cycle and its correlated infertility. Interconnections between PCOS, obesity, and insulin resistance have been recently investigated thoroughly in the scientific community; these findings directed PCOS therapies into unraveling possibilities to target insulin resistance and central adiposity as efficient treatment. On the other hand, brown adipose tissue is known to possess a thermogenic activity that increases lipolysis and directly attenuates fat deposition. Therefore, brown adipose tissue activation lands itself as a potential target for reducing obesity and its induced insulin resistance, subsequently rescuing PCOS phenotypes. In addition, regenerative medicine has proven efficacy in resolving PCOS-associated infertility and its metabolic symptoms. In particular, many stem/progenitor cells have been verified to possess the differentiation capacity into functional brown adipocytes. Thus, throughout this review, we will discuss the different brown adipose tissue activation strategies and stem-cell-based therapies applied to PCOS models and the possible combination of both therapeutic approaches to synergistically act on the activation of brown adipose tissue and attenuate PCOS-correlated infertility and retract the consequences of the metabolic syndrome on the physiological state of patients.
Graphical Abstract
... Energy homeostasis resides in the balance between energy intake that mainly comes from food consumption and energy expenditure which represents the basic metabolic processes and exercises. The process of BAT non-shivering thermogenesis is an important component of energy expenditure (Seale and Lazar, 2009;Saito, 2013). In addition to its thermoregulatory function in cold environments, the BAT can turn excess energy into heat to maintain the energy balance in rodents and humans (Nakamura and Nakamura, 2018). ...
Oxytocin (OT) is a neurohormone involved early in neurodevelopment and is implicated in multiple functions, including sensory modulation. Evidence of such modulation has been observed for different sensory modalities in both healthy and pathological conditions. This review summarizes the pleiotropic modulation that OT can exercise on an often overlooked sensory system: thermosensation. This system allows us to sense temperature variations and compensate for the variation to maintain a stable core body temperature. Oxytocin modulates autonomic and behavioral mechanisms underlying thermoregulation at both central and peripheral levels. Hyposensitivity or hypersensitivity for different sensory modalities, including thermosensitivity, is a common feature in autism spectrum disorder (ASD), recapitulated in several ASD mouse models. These sensory dysregulations occur early in post-natal development and are correlated with dysregulation of the oxytocinergic system. In this study, we discussed the potential link between thermosensory atypia and the dysregulation of the oxytocinergic system in ASD.
... ApoM is mainly produced in the liver and kidney in humans 24,25 , while a minor part may be produced by white adipocytes 26 . In addition to activating BAT, cold exposure also results in sympathetic activation of other organs including WAT 27 . Thus, β-adrenergic activation could influence apoM secretion from WAT. ...
The HDL-associated apolipoprotein M (apoM) and its ligand sphingosine-1-phosphate (S1P) may control energy metabolism. ApoM deficiency in mice is associated with increased vascular permeability, brown adipose tissue (BAT) mass and activity, and protection against obesity. In the current study, we explored the connection between plasma apoM/S1P levels and parameters of BAT as measured via ¹⁸F-FDG PET/CT after cold exposure in humans. Fixed (n = 15) vs personalized (n = 20) short-term cooling protocols decreased and increased apoM (− 8.4%, P = 0.032 vs 15.7%, P < 0.0005) and S1P (− 41.0%, P < 0.0005 vs 19.1%, P < 0.005) plasma levels, respectively. Long-term cooling (n = 44) did not affect plasma apoM or S1P levels. Plasma apoM and S1P did not correlate significantly to BAT volume and activity in the individual studies. However, short-term studies combined, showed that increased changes in plasma apoM correlated with BAT metabolic activity (β: 0.44, 95% CI [0.06–0.81], P = 0.024) after adjusting for study design but not BAT volume (β: 0.39, 95% CI [− 0.01–0.78], P = 0.054). In conclusion, plasma apoM and S1P levels are altered in response to cold exposure and may be linked to changes in BAT metabolic activity but not BAT volume in humans. This contrasts partly with observations in animals and highlights the need for further studies to understand the biological role of apoM/S1P complex in human adipose tissue and lipid metabolism.
