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1.
12,13-diHOME as a new therapeutic target for metabolic diseases.
Macêdo, APA, Muñoz, VR, Cintra, DE, Pauli, JR
Life sciences. 2022;:120229
Abstract
Lipokines are bioactive compounds, derived from adipose tissue depots, that control several molecular signaling pathways. Recently, 12,13-dihydroxy-9Z-octadecenoic acid (12,13-diHOME), an oxylipin, has gained prominence in the scientific literature. An increase in circulating 12,13-diHOME has been associated with improved metabolic health, and the action of this molecule appears to be mediated by brown adipose tissue (BAT). Scientific evidence indicates that the increase in serum levels of 12,13-diHOME caused by stimuli such as physical exercise and exposure to cold may favor the absorption of fatty acids by brown adipose tissue and stimulate the browning process in white adipose tissue (WAT). Thus, strategies capable of increasing 12,13-diHOME levels may be promising for the prevention and treatment of obesity and metabolic diseases. This review explores the relationship of 12,13-diHOME with brown adipose tissue and its role in the metabolic health context, as well as the signaling pathways involved between 12,13-diHOME and BAT.
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Posterior Cervical Brown Fat and CXCL14 Levels in the First Year of Life: Sex Differences and Association With Adiposity.
Garcia-Beltran, C, Cereijo, R, Plou, C, Gavaldà-Navarro, A, Malpique, R, Villarroya, J, López-Bermejo, A, de Zegher, F, Ibáñez, L, Villarroya, F
The Journal of clinical endocrinology and metabolism. 2022;(3):e1148-e1158
Abstract
CONTEXT Brown adipose tissue (BAT) is particularly abundant in neonates, but its association with measures of adiposity and metabolic health in early infancy is poorly delineated. Besides sustaining nonshivering thermogenesis, BAT secretes brown adipokines that act on systemic metabolism. The chemokine CXCL14 has been identified as a brown adipokine in experimental studies. OBJECTIVE To determine the relationships among BAT activity, adiposity, and circulating CXCL14 levels in the first year of life in girls and boys. METHODS Indices of fat accretion, circulating endocrine-metabolic parameters and serum CXCL14 levels were assessed longitudinally in a cohort of infants at birth and at 4 and 12 months. BAT activity was estimated using infrared thermography only at age 12 months.The main outcome measures were weight and length Z-scores, total and abdominal fat content (by dual X-ray absorptiometry), BAT activity at the posterior cervical and supraclavicular regions, serum levels of glucose, insulin, insulin-like growth factor-I, high-molecular-weight adiponectin, and CXCL14; CXCL14 transcript levels in neonatal BAT and liver. RESULTS Posterior cervical BAT was more active in girls than in boys (P = .02). BAT activity was negatively associated with adiposity parameters only in girls. CXCL14 levels were higher in girls than in boys at age 12 months and correlated positively with the area of active posterior cervical BAT in girls. Neonatal BAT showed high CXCL14 gene expression levels. CONCLUSION BAT activity and the levels of CXCL14-a potential surrogate of BAT activity-are sex specific in the first year of life. Posterior cervical BAT activity associates negatively with indices of adiposity only in girls.
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Nutritional Regulation of Human Brown Adipose Tissue.
Suchacki, KJ, Stimson, RH
Nutrients. 2021;(6)
Abstract
The recent identification of brown adipose tissue in adult humans offers a new strategy to increase energy expenditure to treat obesity and associated metabolic disease. While white adipose tissue (WAT) is primarily for energy storage, brown adipose tissue (BAT) is a thermogenic organ that increases energy expenditure to generate heat. BAT is activated upon cold exposure and improves insulin sensitivity and lipid clearance, highlighting its beneficial role in metabolic health in humans. This review provides an overview of BAT physiology in conditions of overnutrition (obesity and associated metabolic disease), undernutrition and in conditions of altered fat distribution such as lipodystrophy. We review the impact of exercise, dietary macronutrients and bioactive compounds on BAT activity. Finally, we discuss the therapeutic potential of dietary manipulations or supplementation to increase energy expenditure and BAT thermogenesis. We conclude that chronic nutritional interventions may represent a useful nonpharmacological means to enhance BAT mass and activity to aid weight loss and/or improve metabolic health.
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Cold Exposure Distinctively Modulates Parathyroid and Thyroid Hormones in Cold-Acclimatized and Non-Acclimatized Humans.
Kovaničová, Z, Kurdiová, T, Baláž, M, Štefanička, P, Varga, L, Kulterer, OC, Betz, MJ, Haug, AR, Burger, IA, Kiefer, FW, et al
Endocrinology. 2020;(7)
Abstract
Cold-induced activation of thermogenesis modulates energy metabolism, but the role of humoral mediators is not completely understood. We aimed to investigate the role of parathyroid and thyroid hormones in acute and adaptive response to cold in humans. Examinations were performed before/after 15 minutes of ice-water swimming (n = 15) or 120 to 150 minutes of cold-induced nonshivering thermogenesis (NST) applied to cold-acclimatized (n = 6) or non-acclimatized (n = 11) individuals. Deep-neck brown adipose tissue (BAT) was collected from non-acclimatized patients undergoing elective neck surgery (n = 36). Seasonal variations in metabolic/hormonal parameters of ice-water swimmers were evaluated. We found that in ice-water swimmers, PTH and TSH increased and free T3, T4 decreased after a 15-minute winter swim, whereas NST-inducing cold exposure failed to regulate PTH and free T4 and lowered TSH and free T3. Ice-water swimming-induced increase in PTH correlated negatively with systemic calcium and positively with phosphorus. In non-acclimatized men, NST-inducing cold decreased PTH and TSH. Positive correlation between systemic levels of PTH and whole-body metabolic preference for lipids as well as BAT volume was found across the 2 populations. Moreover, NST-cooling protocol-induced changes in metabolic preference for lipids correlated positively with changes in PTH. Finally, variability in circulating PTH correlated positively with UCP1/UCP1, PPARGC1A, and DIO2 in BAT from neck surgery patients. Our data suggest that regulation of PTH and thyroid hormones during cold exposure in humans varies by cold acclimatization level and/or cold stimulus intensity. Possible role of PTH in NST is indicated by its positive relationships with whole-body metabolic preference for lipids, BAT volume, and UCP1 content.
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The role of brown adipose tissue and the thermogenic adipocytes in glucose metabolism: recent advances and open questions.
Chondronikola, M
Current opinion in clinical nutrition and metabolic care. 2020;(4):282-287
Abstract
PURPOSE OF REVIEW Brown adipose tissue (BAT) and the thermogenic adipocytes in white adipose tissue (WAT) are considered emerging targets against obesity-related metabolic perturbations given their high capacity for thermogenesis and glucose and lipid disposal. This manuscript summarizes and critically evaluates the recent advances on the role of BAT and thermogenic adipocytes in glucose homeostasis in humans. RECENT FINDINGS Recent studies support that BAT has high capacity for glucose disposal not only during cold but during rewarming and thermoneutrality as well. Moreover, BAT is now considered a metabolic sink for the disposal of branched-chain amino acids improving whole-body glucose metabolism in rodents and, potentially, in humans. β3 adrenergic agonism and glucagon-like peptide 1 increase BAT metabolic activity for glucose and/or induce the browning of WAT. Finally, recent findings support the association of glucose disposal in BAT with subclinical atherosclerosis and the reproducibility of two advanced medical imaging methods for the assessment of BAT using a glucose radiotracer. SUMMARY Recent studies provide new insights on the role of human BAT and thermogenic adipocytes in glucose metabolism. However, further research is needed to unequivocally establish the clinical significance of BAT and the thermogenic adipocytes in glucose homeostasis in humans.
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6.
Brown adipose tissue volume and 18F-fluorodeoxyglucose uptake are not associated with energy intake in young human adults.
Sanchez-Delgado, G, Acosta, FM, Martinez-Tellez, B, Finlayson, G, Gibbons, C, Labayen, I, Llamas-Elvira, JM, Gil, A, Blundell, JE, Ruiz, JR
The American journal of clinical nutrition. 2020;(2):329-339
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Abstract
BACKGROUND Several studies have explored the role of human brown adipose tissue (BAT) in energy expenditure. However, the link between BAT and appetite regulation needs to be more rigorously examined. OBJECTIVES We aimed to investigate the associations of BAT volume and 18F-fluordeoxyglucose (18F-FDG) uptake after a personalized cold exposure with energy intake and appetite-related sensations in young healthy humans. METHODS A total of 102 young adults (65 women; age: 22.08 ± 2.17 y; BMI: 25.05 ± 4.93 kg/m 2) took part in this cross-sectional study. BAT volume, BAT 18F-FDG uptake, and skeletal muscle 18F-FDG uptake were assessed by means of static 18F-FDG positron-emission tomography and computed tomography scans after a 2-h personalized exposure to cold. Energy intake was estimated via an objectively measured ad libitum meal and three nonconsecutive 24-h dietary recalls. Appetite-related sensations (i.e., hunger and fullness) were recorded by visual analog scales before and after a standardized breakfast (energy content = 50% of basal metabolic rate) and the ad libitum meal. Body composition was assessed by a whole-body DXA scan. RESULTS BAT volume and 18F-FDG uptake were not associated with quantified ad libitum energy intake (all P > 0.088), nor with habitual energy intake estimated from the 24-h dietary recalls (all P > 0.683). Lean mass was positively associated with both the energy intake from the ad libitum meal (β: 17.612, R2 = 0.213; P < 0.001) and the habitual energy intake (β: 16.052, R2 = 0.123; P = 0.001). Neither the interaction BAT volume × time elapsed after meal consumption nor that of BAT 18F-FDG uptake × time elapsed after meal consumption had any significant influence on appetite-related sensations after breakfast or after meal consumption (all P > 0.3). CONCLUSIONS Neither BAT volume, nor BAT 18F-FDG uptake after cold stimulation, are related to appetite regulation in young adults. These results suggest BAT plays no important role in the regulation of energy intake in humans.This trial was registered at clinicaltrials.gov as NCT02365129.
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The Transcriptional Role of Vitamin A and the Retinoid Axis in Brown Fat Function.
Herz, CT, Kiefer, FW
Frontiers in endocrinology. 2020;:608
Abstract
In recent years, brown adipose tissue (BAT) has gained significance as a metabolic organ dissipating energy through heat production. Promotion of a thermogenic program in fat holds great promise as potential therapeutic tool to counteract weight gain and related sequelae. Current research efforts are aimed at identifying novel pathways regulating brown fat function and the transformation of white adipocytes into BAT-like cells, a process called "browning." Besides numerous genetic factors some circulating molecules can act as mediators of adipose tissue thermogenesis. Vitamin A metabolites, the retinoids, are potent regulators of gene transcription through nuclear receptor signaling and are thus involved in a plethora of metabolic processes. Accumulating evidence links retinoid action to brown fat function and browning of WAT mainly via orchestrating a transcriptional BAT program in adipocytes including expression of key thermogenic genes such as uncoupling protein 1. Here we summarize the current understanding how retinoids play a role in adipose tissue thermogenesis through transcriptional control of thermogenic gene cassettes and potential non-genomic mechanisms.
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A systematic review on the role of infrared thermography in the Brown adipose tissue assessment.
Brasil, S, Renck, AC, de Meneck, F, Brioschi, ML, Costa, EF, Teixeira, MJ
Reviews in endocrine & metabolic disorders. 2020;(1):37-44
Abstract
Brown adipose tissue (BAT) is an endocrine adipose tissue with attributes to dissipate energy as heat in response to changes in temperature and diet. Infrared thermography (IRT) has been studied in recent years in the assessment of BAT thermogenesis, as an option to positron emission tomography - computed tomography (PET-CT), because of several advantages. We performed a systematic review on the use of IRT in BAT assessment. Comprehensive online search was performed in different databases. The QUADAS 2 tool was used to evaluate studies' quality. 12 studies fit the inclusion criteria, whereas only one of these was considered of low risk of bias. 10 studies were favorable to IRT appliance in BAT evaluation, observing elevation of supraclavicular skin temperature correlated with BAT activity. Studies were heterogeneous in design, and a meta-analysis was precluded. Further studies with similar methodologies are needed. Conclusion: Despite the large number of published methodologies, IRT is a promising method for detecting BAT activation. Current knowledge already allows a better understanding of thermography to improve and standardize the technique.
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Effects of Capsinoid Intake on Brown Adipose Tissue Vascular Density and Resting Energy Expenditure in Healthy, Middle-Aged Adults: A Randomized, Double-Blind, Placebo-Controlled Study.
Fuse, S, Endo, T, Tanaka, R, Kuroiwa, M, Ando, A, Kume, A, Yamamoto, A, Kuribayashi, K, Somekawa, S, Takeshita, M, et al
Nutrients. 2020;(9)
Abstract
Capsinoids are some of the most promising ingredients to increase energy expenditure (EE) due to brown adipose tissue (BAT) activation. However, there is limited information regarding the effect of prolonged capsinoid ingestion (CI) on BAT activity and resting EE (REE) in healthy, middle-aged, normal to overweight subjects (Subhealthy) with distinct BAT characteristics. We examined the changes in BAT density (BAT-d), using near-infrared time-resolved spectroscopy, and REE/kg induced by daily CI. Forty Subhealthy [age, 43.8 (mean) years; BMI, 25.4 kg/m2] received either capsinoid (9 mg/day) or a placebo daily for 6 weeks in a double-blind design. Total hemoglobin concentration in the supraclavicular region ([total-Hb]sup), an indicator of BAT-d, and REE/kg were measured. The changes in post-intervention [total-Hb]sup were greater in the capsinoid group (CA-G) than in the placebo group (PL-G) [5.8 µM (+12.4%) versus 1.0 µM (+2.1%); p = 0.017]. There was a significant relationship between BAT-d and REE/kg; however, post-supplementation REE/kg was not significantly different between the two groups (p = 0.228). In the overweight subgroup, changes in REE/kg were greater in the CA-G than in the PL-G [0.6 cal/kg/min (+4.3%) versus -0.3 cal/kg/min (-2.1%); p = 0.021]. CI enhanced [total-Hb]sup, a reflection of BAT-d, showing a good correlation with REE in Subhealthy.
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10.
Infrared Thermography for Estimating Supraclavicular Skin Temperature and BAT Activity in Humans: A Systematic Review.
Jimenez-Pavon, D, Corral-Perez, J, Sánchez-Infantes, D, Villarroya, F, Ruiz, JR, Martinez-Tellez, B
Obesity (Silver Spring, Md.). 2019;(12):1932-1949
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Abstract
OBJECTIVE Brown adipose tissue (BAT) is a thermogenic tissue with potential as a therapeutic target in the treatment of obesity and related metabolic disorders. The most used technique for quantifying human BAT activity is the measurement of 18 F-fluorodeoxyglucose uptake via a positron emission tomography/computed tomography scan following exposure to cold. However, several studies have indicated the measurement of the supraclavicular skin temperature (SST) by infrared thermography (IRT) to be a less invasive alternative. This work reviews the state of the art of this latter method as a means of determining BAT activity in humans. METHODS The data sources for this review were PubMed, Web of Science, and EBSCOhost (SPORTdiscus), and eligible studies were those conducted in humans. RESULTS In most studies in which participants were first cooled, an increase in IRT-measured SST was noted. However, only 5 of 24 such studies also involved a nuclear technique that confirmed increased activity in BAT, and only 2 took into account the thickness of the fat layer when measuring SST by IRT. CONCLUSIONS More work is needed to understand the involvement of tissues other than BAT in determining IRT-measured SST; at present, IRT cannot determine whether any increase in SST is due to increased BAT activity.