Brown Adipose Tissue Activity Research Articles

A device for rapid calorimetric measurements on small biological tissue samples

AbstractA new calorimetric technique is described that allows high-throughput heat production rate measurements on small biological tissue samples. The technique is based on the widely used thermopile chip technology combined with an innovative method for precise transport and positioning of samples of different biological materials at the thermal power detector inside the calorimeter. The new transport and positioning technique is a combination of fluidic and mechanical transport, where the latter is realized by a magneto-motor drive. The transport facility ensures good diffusive oxygen penetration into the sample, which is essential for highly metabolically active materials. The proper functioning of the device is demonstrated by measuring the heat production of metabolically active brown adipose tissue, biopsied tegu lizard muscle, and live Drosophila larvae at different stages and temperatures.

The histone methyltransferase SUV420H2 regulates brown and beige adipocyte thermogenesis.

Activation of brown adipose tissue (BAT) thermogenesis increases energy expenditure and alleviates obesity. Here we discover that histone methyltransferase suppressor of variegation 4-20 homolog 2 (Suv420h2) expression parallels that of Ucp1 in brown and beige adipocytes and that Suv420h2 knockdown significantly reduces, whereas Suv420h2 overexpression significantly increases Ucp1 levels in brown adipocytes. Suv420h2 knockout (H2KO) mice exhibit impaired cold-induced thermogenesis and are prone to diet-induced obesity. In contrast, mice with specific overexpression of Suv420h2 in adipocytes display enhanced cold-induced thermogenesis and are resistant to diet-induced obesity. Further study shows that Suv420h2 catalyzes H4K20 trimethylation at eukaryotic translation initiation factor 4E-binding protein 1 (4e-bp1) promoter, leading to down-regulated expression of 4e-bp1, a negative regulator of the translation initiation complex. This in turn up-regulates PGC1α protein levels, which is associated with increased expression of thermogenic program. We conclude that Suv420h2 is a key regulator of brown/beige adipocyte development and thermogenesis.

The beta-2-adrenoreceptor agonist fenoterol increases resting enery expenditure without activation of brown adipose tissue in humans

The beta-2-adrenoreceptor agonist fenoterol increases resting enery expenditure without activation of brown adipose tissue in humans

Brown adipose tissue activation on 18FDG-PET/CT scan in phaeochromocytoma: A case series

Brown adipose tissue activation on 18FDG-PET/CT scan in phaeochromocytoma: A case series

Brown adipose tissue metabolism in women is dependent on ovarian status.

In rodents, loss of estradiol (E2) reduces brown adipose tissue (BAT) metabolic activity. Whether E2 impacts BAT activity in women is not known. BAT oxidative metabolism was measured in premenopausal (n = 27; 35 ± 9 yr; body mass index = 26.0 ± 5.3 kg/m2) and postmenopausal (n = 25; 51 ± 8 yr; body mass index = 28.0 ± 5.0 kg/m2) women at room temperature and during acute cold exposure using [11C]acetate with positron emission tomography coupled with computed tomograph. BAT glucose uptake was also measured during acute cold exposure using 2-deoxy-2-[18F]fluoro-d-glucose. To isolate the effects of ovarian hormones from biological aging, measurements were repeated in a subset of premenopausal women (n = 8; 40 ± 4 yr; BMI = 28.0 ± 7.2 kg/m2) after 6 mo of gonadotropin-releasing hormone agonist therapy to suppress ovarian hormones. At room temperature, there was no difference in BAT oxidative metabolism between premenopausal (0.56 ± 0.31 min-1) and postmenopausal women (0.63 ± 0.28 min-1). During cold exposure, BAT oxidative metabolism (1.28 ± 0.85 vs. 0.91 ± 0.63 min-1, P = 0.03) and net BAT glucose uptake (84.4 ± 82.5 vs. 29.7 ± 31.4 nmol·g-1·min-1, P < 0.01) were higher in premenopausal than postmenopausal women. In premenopausal women who underwent gonadotropin-releasing hormone agonist, cold-stimulated BAT oxidative metabolism was reduced to a similar level (from 1.36 ± 0.66 min-1 to 0.91 ± 0.41 min-1) to that observed in postmenopausal women (0.91 ± 0.63 min-1). These results provide the first evidence in humans that reproductive hormones are associated with BAT oxidative metabolism and suggest that BAT may be a target to attenuate age-related reduction in energy expenditure and maintain metabolic health in postmenopausal women.NEW & NOTEWORTHY In rodents, loss of estrogen reduces brown adipose tissue (BAT) activity. Whether this is true in humans is not known. We found that BAT oxidative metabolism and glucose uptake were lower in postmenopausal compared to premenopausal women. In premenopausal women who underwent ovarian suppression to reduce circulating estrogen, BAT oxidative metabolism was reduced to postmenopausal levels. Thus the loss of ovarian function in women leads to a reduction in BAT metabolic activity independent of age.

Sulfonylureas exert antidiabetic action on adipocytes by inhibition of PPARγ serine 273 phosphorylation

ObjectiveSulfonylureas (SUs) are still among the mostly prescribed antidiabetic drugs with an established mode of action: release of insulin from pancreatic β-cells. In addition, effects of SUs on adipocytes by activation of the nuclear receptor peroxisome proliferator-activated receptor γ (PPARγ) have been described, which might explain their insulin-sensitizing potential observed in patients. However, there is a discrepancy between the impact of SUs on antidiabetic action and their rather moderate in vitro effect on PPARγ transcriptional activity. Recent studies have shown that some PPARγ ligands can improve insulin sensitivity by blocking PPARγ Ser-273 phosphorylation without having full agonist activity. It is unknown if SUs elicit their antidiabetic effects on adipocytes by inhibition of PPARγ phosphorylation. Here, we investigated if binding of SUs to PPARγ can interfere with PPARγ Ser-273 phosphorylation and determined their antidiabetic actions in vitro in primary human white adipocytes and in vivo in high-fat diet (HFD) obese mice. MethodsPrimary human white preadipocytes were differentiated in the presence of glibenclamide, glimepiride and PPARγ ligands rosiglitazone and SR1664 to compare PPARγ Ser-273 phosphorylation, glucose uptake and adipokine expression. Transcriptional activity at PPARγ was determined by luciferase assays, quantification of PPARγ Ser-273 phosphorylation was determined by Western blotting and CDK5 kinase assays. In silico modelling was performed to gain insight into the binding characteristics of SUs to PPARγ. HFD mice were administered SUs and rosiglitazone for 6 days. PPARγ Ser-273 phosphorylation in white adipose tissue (WAT), body composition, glucose tolerance, adipocyte morphology and expression levels of genes involved in PPARγ activity in WAT and brown adipose tissue (BAT) were evaluated. ResultsSUs inhibit phosphorylation of PPARγ at Ser-273 in primary human white adipocytes and exhibit a positive antidiabetic expression profile, which is characterized by up regulation of insulin-sensitizing and down regulation of insulin resistance-inducing adipokines. We demonstrate that SUs directly bind to PPARγ by in silico modelling and inhibit phosphorylation in kinase assays to a similar extend as rosiglitazone and SR1664. In HFD mice SUs reduce PPARγ phosphorylation in WAT and have comparable effects on gene expression to rosiglitazone. In BAT SUs increase UCP1 expression and reduce lipid droplets sizes. ConclusionsOur findings indicate that a part of SUs extra-pancreatic effects on adipocytes in vitro and in vivo is probably mediated via their interference with PPARγ phosphorylation rather than via classical agonistic activity at clinical concentrations.

Unveiling the Potential of Natural Compounds: A Comprehensive Review on Adipose Thermogenesis Modulation.

The process of adipocyte browning has recently emerged as a novel therapeutic target for combating obesity and obesity-related diseases. Non-shivering thermogenesis is the process of biological heat production in mammals and is primarily mediated via brown adipose tissue (BAT). The recruitment and activation of BAT can be induced through chemical drugs and nutrients, with subsequent beneficial health effects through the utilization of carbohydrates and fats to generate heat to maintain body temperature. However, since potent drugs may show adverse side effects, nutritional or natural substances could be safe and effective as potential adipocyte browning agents. This review aims to provide an extensive overview of the natural food compounds that have been shown to activate brown adipocytes in humans, animals, and in cultured cells. In addition, some key genetic and molecular targets and the mechanisms of action of these natural compounds reported to have therapeutic potential to combat obesity are discussed.

Cold-induced expression of a truncated adenylyl cyclase 3 acts as rheostat to brown fat function.

Promoting brown adipose tissue (BAT) activity innovatively targets obesity and metabolic disease. While thermogenic activation of BAT is well understood, the rheostatic regulation of BAT to avoid excessive energy dissipation remains ill-defined. Here, we demonstrate that adenylyl cyclase 3 (AC3) is key for BAT function. We identified a cold-inducible promoter that generates a 5' truncated AC3 mRNA isoform (Adcy3-at), whose expression is driven by a cold-induced, truncated isoform of PPARGC1A (PPARGC1A-AT). Male mice lacking Adcy3-at display increased energy expenditure and are resistant to obesity and ensuing metabolic imbalances. Mouse and human AC3-AT are retained in the endoplasmic reticulum, unable to translocate to the plasma membrane and lack enzymatic activity. AC3-AT interacts with AC3 and sequesters it in the endoplasmic reticulum, reducing the pool of adenylyl cyclases available for G-protein-mediated cAMP synthesis. Thus, AC3-AT acts as a cold-induced rheostat in BAT, limiting adverse consequences of cAMP activity during chronic BAT activation.

Main mechanisms and clinical implications of alterations in energy expenditure state among patients with pheochromocytoma and paraganglioma: A review.

Pheochromocytoma and paraganglioma (PPGL) are rare neuroendocrine tumors with diverse clinical presentations. Alterations in energy expenditure state are commonly observed in patients with PPGL. However, the reported prevalence of hypermetabolism varies significantly and the underlying mechanisms and implications of this presentation have not been well elucidated. This review discusses and analyzes the factors that contribute to energy consumption. Elevated catecholamine levels in patients can significantly affect substance and energy metabolism. Additionally, changes in the activation of brown adipose tissue (BAT), inflammation, and the inherent energy demands of the tumor can contribute to increased resting energy expenditure (REE) and other energy metabolism indicators. The PPGL biomarker, chromogranin A (CgA), and its fragments also influence energy metabolism. Chronic hypermetabolic states may be detrimental to these patients, with surgical tumor removal remaining the primary therapeutic intervention. The high energy expenditure of PPGL has not received the attention it deserves, and an accurate assessment of energy metabolism is the cornerstone for an adequate understanding and treatment of the disease.

Ginsenoside Rg3, enriched in red ginseng extract, improves lipopolysaccharides-induced suppression of brown and beige adipose thermogenesis with mitochondrial activation

Brown adipose tissue (BAT) which is a critical regulator of energy homeostasis, and its activity is inhibited by obesity and low-grade chronic inflammation. Ginsenoside Rg3, the primary constituent of Korean red ginseng (steamed Panax ginseng CA Meyer), has shown therapeutic potential in combating inflammatory and metabolic diseases. However, it remains unclear whether Rg3 can protect against the suppression of browning or activation of BAT induced by inflammation. In this study, we conducted a screening of ginsenoside composition in red ginseng extract (RGE) and explored the anti-adipogenic effects of both RGE and Rg3. We observed that RGE (exist 0.25 mg/mL of Rg3) exhibited significant lipid-lowering effects in adipocytes during adipogenesis. Moreover, treatment with Rg3 (60 μM) led to the inhibition of triglyceride accumulation, subsequently promoting enhanced fatty acid oxidation, as evidenced by the conversion of radiolabeled 3H-fatty acids into 3H-H2O with mitochondrial activation. Rg3 alleviated the attenuation of browning in lipopolysaccharide (LPS)-treated beige adipocytes and primary brown adipocytes by recovered by uncoupling protein 1 (UCP1) and the oxygen consumption rate compared to the LPS-treated group. These protective effects of Rg3 on inflammation-induced inhibition of beige and BAT-derived thermogenesis were confirmed in vivo by treating with CL316,243 (a beta-adrenergic receptor agonist) and LPS to induce browning and inflammation, respectively. Consistent with the in vitro data, treatment with Rg3 (2.5 mg/kg, 8 weeks) effectively reversed the LPS-induced inhibition of brown adipocyte features in C57BL/6 mice. Our findings confirm that Rg3-rich foods are potential browning agents that counteract chronic inflammation and metabolic complications.

Genetic evidence for involvement of β2-adrenergic receptor in brown adipose tissue thermogenesis in humans.

Sympathetic activation of brown adipose tissue (BAT) thermogenesis can ameliorate obesity and related metabolic abnormalities. However, crucial subtypes of the β-adrenergic receptor (AR), as well as effects of its genetic variants on functions of BAT, remains unclear in humans. We conducted association analyses of genes encoding β-ARs and BAT activity in human adults. Single nucleotide polymorphisms (SNPs) in β1-, β2-, and β3-AR genes (ADRB1, ADRB2, and ADRB3) were tested for the association with BAT activity under mild cold exposure (19 °C, 2 h) in 399 healthy Japanese adults. BAT activity was measured using fluorodeoxyglucose-positron emission tomography and computed tomography (FDG-PET/CT). To validate the results, we assessed the effects of SNPs in the two independent populations comprising 277 healthy East Asian adults using near-infrared time-resolved spectroscopy (NIRTRS) or infrared thermography (IRT). Effects of SNPs on physiological responses to intensive cold exposure were tested in 42 healthy Japanese adult males using an artificial climate chamber. We found a significant association between a functional SNP (rs1042718) in ADRB2 and BAT activity assessed with FDG-PET/CT (p < 0.001). This SNP also showed an association with cold-induced thermogenesis in the population subset. Furthermore, the association was replicated in the two other independent populations; BAT activity was evaluated by NIRTRS or IRT (p < 0.05). This SNP did not show associations with oxygen consumption and cold-induced thermogenesis under intensive cold exposure, suggesting the irrelevance of shivering thermogenesis. The SNPs of ADRB1 and ADRB3 were not associated with these BAT-related traits. The present study supports the importance of β2-AR in the sympathetic regulation of BAT thermogenesis in humans. The present collection of DNA samples is the largest to which information on the donor's BAT activity has been assigned and can serve as a reference for further in-depth understanding of human BAT function.

Plasticity of Adipose Tissues: Interconversion among White, Brown, and Beige Fat and Its Role in Energy Homeostasis.

Obesity, characterized by the excessive accumulation of adipose tissue, has emerged as a major public health concern worldwide. To develop effective strategies for treating obesity, it is essential to comprehend the biological properties of different adipose tissue types and their respective roles in maintaining energy balance. Adipose tissue serves as a crucial organ for energy storage and metabolism in the human body, with functions extending beyond simple fat storage to encompass the regulation of energy homeostasis and the secretion of endocrine factors. This review provides an overview of the key characteristics, functional differences, and interconversion processes among white adipose tissue (WAT), brown adipose tissue (BAT), and beige adipose tissue. Moreover, it delves into the molecular mechanisms and recent research advancements concerning the browning of WAT, activation of BAT, and whitening of BAT. Although targeting adipose tissue metabolism holds promise as a potential approach for obesity treatment, further investigations are necessary to unravel the intricate biological features of various adipose tissue types and elucidate the molecular pathways governing their interconversion. Such research endeavors will pave the way for the development of more efficient and targeted therapeutic interventions in the fight against obesity.

Obesity in the 21st Century. Prevalence, Phenotypes, Course Variants and Consequences

The review article examines the issues of obesity regarding its prevalence, phenotypes, course and consequences. The anatomical, physiological and functional features of adipose tissue are discussed. The “Discussion” section presents the authors’ own clinical observations on therapeutic and surgical issues in the treatment of obesity. Currently, adipose tissue is divided into white, brown and beige. White and brown adipose tissue can turn into each other through the beige adipose tissue stage. The volume and activity of brown adipose tissue require greater expenditure in the metabolism of oxygen molecules and are more pronounced in women. The components of the extracellular matrix of adipose tissue are collagen types I, III, V, VI. The collagen structure of adipose tissue varies depending on the location, volume and size of fat, age, gender, functional state of the kidneys, thyroid gland, nature of food, energy expenditure and sleep patterns. With intense work and cold exposure, the hormone irisin is formed in skeletal muscles, which promotes the transformation of white adipose tissue into brown or beige, helps reduce body weight in obesity, and has a beneficial effect on the course of type 2 diabetes mellitus and associated diseases. Traditionally, obese individuals are divided into metabolically healthy obesity and metabolically unhealthy obesity based on the degree of metabolic disorders. In visceral fat, lipolysis occurs with high intensity, which supports the development of inflammation. In obesity, decreased expression of adiponectin accelerates the development of atherosclerotic cardiovascular diseases. As body weight increases, visceral adipose tissue acquires an inflammatory phenotype, manifested by increased expression of cytokines (interleukin-6, interleukin-1, interleukin-17, tumor necrosis factor-alpha), hyperactivation of the tissue renin-angiotensin-aldosterone system, as well as excessive cell infiltration immune system (leukocytes, neutrophils, T-lymphocytes, monocytes, macrophages). During inflammation in adipose tissue, inflammatory (M1) and atherogenic (M4) phenotypes of macrophages dominate. In morbid obesity, the number of macrophages in adipose tissue can reach up to 50% of all cells.

Possible Anti-Obesity Role of Flavonoids Through Brown Adipose Tissue

Worldwide, the incidence of overweight and obesity is increasing day by day, and this makes the control of body weight and complications a primary health problem. Weight loss diet therapy has long been a primary role in the prevention and management of obesity. Evidence supporting the specific anti-obesity effects of certain nutrient components, in particular, polyphenolic compounds, are increasing, as well as a strategy to limit energy intake to achieve control of body weight. Active brown adipose tissue in adult individuals is gaining interest as a new and feasible target for controlling body weight by triggering and increasing energy expenditure. Flavonoids are one of the polyphenolic compounds that draw attention by regulating non-shivering thermogenesis. Although each flavonoid has its health benefits; many phytochemical compounds classified as flavonoids have an anti-obesity effect by regulating oxidation, synthesis, uptake, and transport of fatty acids. In this study, current studies on the therapeutic effect of flavonoids on obesity by regulating energy expenditure through various mechanisms of action in brown adipose tissue are reviewed.

Myricetin ameliorates polycystic ovary syndrome in mice by brown adipose tissue activation.

Brown adipose tissue impaired in polycystic ovary syndrome (PCOS) plays a crucial role in the treatment of PCOS. This study shows that myricetin potently improves PCOS by activating brown adipose tissue (BAT). PCOS is a complex endocrine disease characterized by hyperandrogenism, anovulation and polycystic ovary, and is often accompanied by metabolic disorder such as insulin resistance. BAT has been considered as a promising target for the treatment of obesity and other metabolic disease. In this study, we showed that 3 weeks of myricetin (a compound from natural product) treatment improved metabolic capacity and insulin sensitivity by activating BAT in dehydroepiandrosterone (DHEA)-induced PCOS mice. Furthermore, increased number of corpus luteum and decreased cystic formation were observed in PCOS mice. With the hormone levels such as luteinizing hormone (LH) were reversed, estrous cycle was also normalized after myricetin treatment. Eventually, myricetin markedly improved reproductive defects in PCOS mice. In short, our results suggest that myricetin treatment dramatically ameliorates ovarian dysfunction and metabolic disturbances in PCOS and provides a novel perspective for the treatment of PCOS.

Xiasangju alleviate metabolic syndrome by enhancing noradrenaline biosynthesis and activating brown adipose tissue.

Metabolic syndrome (MetS) is a clinical condition associated with multiple metabolic risk factors leading to type 2 diabetes mellitus and other metabolic diseases. Recent evidence suggests that modulating adipose tissue to adaptive thermogenesis may offer therapeutic potential for MetS. Xiasangju (XSJ) is a marketed drug and dietary supplement used for the treatment of metabolic disease with anti-inflammatory activity. This study investigated the therapeutic effects of XSJ and the underlying mechanisms affecting the activation of brown adipose tissue (BAT) in MetS. The results revealed that XSJ ameliorated MetS by enhancing glucose and lipid metabolism, leading to reduced body weight and abdominal circumference, decreased adipose tissue and liver index, and improved blood glucose tolerance. XSJ administration stimulated catecholamine biosynthesis, increasing noradrenaline (NA) levels and activating NA-mediated proteins in BAT. Thus, BAT enhanced thermogenesis and oxidative phosphorylation (OXPHOS). Moreover, XSJ induced changes in gut microbiota composition, with an increase in Oscillibacter abundance and a decrease in Bilophila, Candidatus Stoquefichus, Holdemania, Parasutterella and Rothia. XSJ upregulated the proteins associated with intestinal tight junctions corresponding with lower serum lipopolysaccharide (LPS), tumor necrosis factor α (TNF-α) monocyte chemoattractant protein-1 (MCP-1) and interleukin-6 (IL-6) levels to maintain NA signaling transport. In summary, XSJ may alleviate MetS by promoting thermogenesis in BAT to ultimately boost energy metabolism through increasing NA biosynthesis, strengthening intestinal barrier integrity and reducing low-grade inflammation. These findings suggest XSJ has potential as a natural therapeutic agent for the treatment of MetS.

Preconceptional capsaicin intervention mitigates negative effects of paternal obesity on metabolic characteristics in male offspring upon high-fat diet challenge

The activation of brown adipose tissue by cold exposure in paternal mice has been reported to improve the metabolic health of offspring. Notably, dietary components for activating BAT have drawn considerable attention owing to their high feasibility for human trials. Therefore, here the potential metabolic improving effects of dietary capsaicin intervention on diet-induced obese paternal mice and their offspring were measured. The results support that paternal preconceptional capsaicin intervention not only elicited the anticipated enhancement of brown fat activity in obese paternal mice, but also improved the metabolic profiles in male offspring evidenced by their elevated resistance to high-fat diet challenge. Moreover, changes in sperm DNA methylation and small non-coding RNA profile were noted in paternal mice with capsaicin intervention, though additional investigation is needed to further delve into the mechanisms. In summary, paternal dietary intervention activating BAT could represent a promising strategy for enhancing the metabolic health of offspring.

Effect of Electroacupuncture Stimulation on Brown Adipose Tissue Thermogenesis.

: Brown adipose tissue (BAT) is a unique thermogenic tissue in mammals mediated by uncoupling protein 1 (UCP1). The energy generated by glucose and triglyceride metabolism is released and transmitted throughout the body as heat. Understanding the factors influencing BAT function is crucial to determine its metabolic significance and effects on overall health. Although studies have shown that electroacupuncture (EA) at specific acupoints (e.g., ST36) can stimulate BAT, its effects at other acupoints are not well understood. Further research is needed to investigate the potential effects of EA at these acupoints and their association with BAT activation. : This study aimed to investigate the effects of EA at the GV20 and EX-HN3 acupoints. Specifically, the effects of EA on BAT thermogenesis were analyzed by infrared thermography, western blotting, and real-time polymerase chain reaction (PCR). : A total of 12 C57BL/6J mice were randomly divided into the EA and control groups. The EA group received EA at GV20 and EX-HN3 for 20 min once daily for 14 days. The control group underwent the same procedure but without EA. The core body temperature was monitored. Infrared thermal images of the back of each mouse in both groups were captured. BAT samples were collected after euthanasia to analyze UCP1 protein and UCP1 mRNA. : The average skin temperature in the scapular region of the EA group was increased by 1.1℃ compared with that of the C group (p < 0.05). Additionally, the average temperature along the governor vessel in the EA group was increased by 1.6℃ (p = 0.045). EA significantly increased the expression of UCP1 protein (p = 0.001) and UCP1 mRNA (p = 0.002) in BAT, suggesting a potential link between EA and BAT thermogenesis. : EA induced BAT thermogenesis, suggesting GV20 and EX-HN3 as potential acupoints for BAT stimulation. The experimental results also highlighted unique meridian characteristics as demonstrated by elevated skin temperature along the governor vessel in mice.

Metabolic Effects of Brown Adipose Tissue Activity Due to Cold Exposure in Humans: A Systematic Review and Meta-Analysis of RCTs and Non-RCTs.

Brown adipose tissue (BAT), specialized in thermoregulation in mammals, has been linked to improved glucose and lipid homeostasis when activated by cold exposure (CE). This systematic review and meta-analysis assessed the metabolic effects of CE-induced BAT activation in healthy humans, examining changes in glucose and lipid metabolism compared to thermoneutrality (TN). A literature search was conducted, identifying relevant human studies, including randomized controlled trials (RCTs) and non-RCTs, based on predefined inclusion criteria. Seven studies (a total of 85 participants) fully met the criteria. Data on plasma glucose, insulin, triglycerides (TGs), and free fatty acids (FFAs) were extracted for meta-analysis. When comparing TN and CE under fasting conditions, there were no significant changes in glucose, insulin, or TG concentrations (all p > 0.36). In contrast, CE significantly increased FFA concentrations (p = 0.002; n = 38). Bias was absent for all parameters, but heterogeneity was observed for insulin (I2 = 74.8%). CE primarily affects FFA concentration, likely reflecting cold-induced BAT activity. This suggests that circulating FFAs, serving as the primary fuel for thermogenesis, could indicate BAT activation. However, understanding the effects of BAT activation on overall metabolism requires a broader approach beyond fasting glucose and lipid concentration measurements.

Brown Adipose Tissue, Batokines, and Bioactive Compounds in Foods: An Update.

The discovery of metabolically active brown adipose tissue (BAT) in human adults and the worldwide increase in obesity and obesity-related chronic noncommunicable diseases (NCDs) has made BAT a therapeutic target in the last two decades. The potential of BAT to oxidize fatty acids rapidly and increase energy expenditure inversely correlates with adiposity, insulin and glucose resistance, and cardiovascular and metabolic diseases. Currently, BAT is recognized by a new molecular signature; several BAT-derived molecules that act positively on target tissues have been identified and collectively called batokines. Bioactive compounds present in foods are endowed with thermogenic properties that increase BAT activation signaling. Understanding the mechanisms that lead to BAT activation and the batokines secreted by it within the thermogenic state is fundamental for its recruitment and management of obesity and NCDs. This review contributes to recent updates on the morphophysiology of BAT, its endocrine role in obesity, and the main bioactive compounds present in foods involved in classical and nonclassical thermogenic pathways activation.