Article

Field and laboratory methods for quantifying brown adipose tissue thermogenesis

June 2019
American Journal of Human Biology 31(2)

Authors:

City University of New York - Hunter College

Non‐shivering thermogenesis (NST) is a metabolic response to acute cold exposure that involves the liberation of chemical energy through physiological mechanisms that are separate from muscle shivering. Recent research suggests that the metabolic and endocrine action of brown adipose tissue (BAT) may play an important role in adult human NST. Thus, characterizing variation in BAT across human populations is of central importance to human biologists interested in human energetics and cardio‐metabolic health. The gold standard for measuring BAT requires positron emission tomography (PET) and computed tomography (CT)—a technique that is expensive, exposes the participant to radiation, and is inaccessible to researchers working in many regions. Here, the author outline a noninvasive, portable alternative approach to quantifying BAT that modifies the protocols commonly used in PET/CT studies. The method consists of three components: (a) activating BAT thermogenesis using a mild cooling condition; (b) indirectly quantifying BAT thermogenesis by measuring the change in skin temperature where BAT is commonly stored using infrared thermal imaging; and (c) estimating NST by measuring the change in energy expenditure using open‐circuit indirect calorimetry. The development of “field‐friendly” methods will allow human biologists to better characterize population variation in BAT as well as its adaptive and health significance.

Brown adipose tissue thermogenesis among a small sample of reindeer herders from sub-Arctic Finland

Article

Full-text available

Apr 2022
J Physiol Anthropol

Introduction Interest in human physiological responses to cold stress have seen a resurgence in recent years with a focus on brown adipose tissue (BAT), a mitochondria dense fat specialized for heat production. However, a majority of the work examining BAT has been conducted among temperate climate populations. Methods To expand our understanding of BAT thermogenesis in a cold climate population, we measured, using indirect calorimetry and thermal imaging, metabolic rate and body surface temperatures of BAT-positive and BAT-negative regions at room temperature, and mild cold exposure of resting participants from a small sample of reindeer herders ( N = 22, 6 females) from sub-Arctic Finland. Results We found that most herders experienced a significant mean 8.7% increase in metabolic rates, preferentially metabolized fatty acids, and maintained relatively warmer body surface temperatures at the supraclavicular region (known BAT location) compared to the sternum, which has no associated BAT. These results indicate that the herders in this sample exhibit active BAT thermogenesis in response to mild cold exposure. Conclusions This study adds to the rapidly growing body of work looking at the physiological and thermoregulatory significance of BAT and the important role it may play among cold stressed populations.

Brown adipose tissue thermogenesis among young adults in northeastern Siberia and Midwest United States and its relationship with other biological adaptations to cold climates

Article

Feb 2022

Objectives: Recent research suggests that brown adipose tissue (BAT) plays a functional role in non-shivering thermogenesis; however, few studies have examined population variation in BAT or its relationship with other mechanisms of adaptation to cold stress. This study characterized BAT thermogenesis and other adaptive responses to low temperatures among Indigenous Siberian young adults and young adults living near Chicago, IL. Materials and methods: We recruited 72 Yakut participants (42 females; 30 males) and 54 participants in Evanston, IL (40 females; 14 males). Anthropometric dimensions and resting metabolic rate (RMR) were measured, and we calculated percent divergence in RMR from expected values (divRMR). We also quantified change in supraclavicular temperature, sternum temperature, and energy expenditure after a mild cooling condition. Results: Participants in Yakutia were less likely to shiver during the cooling condition (p < .05) and exhibited significantly greater evidence of BAT thermogenesis, warmer sternum temperatures, and higher divRMR than participants in Evanston (p < .05). Additionally, the relationship between change in supraclavicular temperature and energy expenditure differed between the two samples. Conclusions: Yakut young adults displayed greater evidence of BAT thermogenesis in response to mild cooling compared with young adults living near Chicago, IL. Furthermore, the relationship between BAT thermogenesis and change in energy expenditure appears to be stronger among Yakut adults. Adults that exhibited greater metabolic response to cold stress, such as higher BAT thermogenesis and divRMR, maintained warmer sternum temperatures. These results highlight the degree to which adaptation to cold climates involves multiple integrated biological pathways.

Weather permitting: Increased seasonal efficiency of nonshivering thermogenesis through brown adipose tissue activation in the winter

Article

Dec 2021

Objectives We investigated seasonal changes in brown adipose tissue (BAT) activation and metabolism in a temperate-climate Albany, NY population. Methods Data were collected among 58 participants (21 males, 37 females, ages: 18–51) in the summer and 59 participants (23 males, 36 females, ages: 18–63) in the winter in Albany, New York. BAT activity was inferred by comparing metabolic rate, heat dissipation in the supraclavicular area, and respiratory quotient at room temperature and cold exposure. Seasonal variation in BAT was determined by comparing these measurements from summer and winter. Results At mild cold exposure, heat dissipation of the supraclavicular area was significantly greater in the winter compared to summer (p < .001); however, no significant differences were found between seasons in metabolic rate measurements. This suggests BAT activation may be metabolically more efficient in the winter, due to prolonged lower seasonal temperatures relative to summer. Respiratory quotient significantly increased upon mild cold exposure in the winter compared to summer (p < .001). While carbohydrate utilization increased in the winter, fat remained the primary metabolic substrate for BAT activity across both seasons. Conclusion The seasonal variations in the effects of nonshivering thermogenesis on metabolic rate and substrate metabolism suggest a buffering of energy expenditure and an increased use of glucose as fuel by BAT as a result of acclimatization to cold in the winter. These findings point towards a potential role of BAT in human whole-body mediated glucose disposal and cold adaptation.

Evidence for a sensitive period of plasticity in brown adipose tissue during early childhood among indigenous Siberians

Article

Apr 2021

Objectives Evolutionary theorists have debated the adaptive significance of developmental plasticity in organisms with long lifespans such as humans. This debate in part stems from uncertainty regarding the timing of sensitive periods. Does sensitivity to environmental signals fluctuate across development or does it steadily decline? We investigated developmental plasticity in brown adipose tissue (BAT) among indigenous Siberians in order to explore the timing of phenotypic sensitivity to cold stress. Methods BAT thermogenesis was quantified using infrared thermal imaging in 78 adults (25 men; 33 women). Cold exposure during gestation, infancy, early childhood, middle childhood, and adolescence was quantified using: (1) the average ambient temperature across each period; (2) the number of times daily temperature dropped below −40°F during each period. We also assessed past cold exposure with a retrospective survey of participation in outdoor activities. Results Adult BAT thermogenesis was significantly associated with the average temperature (p = 0.021), the number of times it was below −40°F (p = 0.026), and participation in winter outdoor activities (p = 0.037) during early childhood. Conclusions Our results suggest that early childhood represents an important stage for developmental plasticity, and that culture may play a critical role in shaping the timing of environmental signals. The findings highlight a new pathway through which the local consequences of global climate change may influence human biology, and they suggest that ambient temperature may represent an understudied component of the developmental origins of health and disease.

The wintertime brown adipose tissue thermogenesis of New York City residents amidst climate change

Article

Full-text available

Feb 2025

Background The built environment buffers residents of large cities, such as New York (NYC), from exposure to low temperatures. Furthermore, average winter temperatures are rising in NYC due to climate change. The degree to which NYC residents exhibit metabolic adaptations to cold stress is currently unclear. Aim This study quantified variation in brown adipose tissue (BAT), energy expenditure (EE), and ambient temperature among NYC residents. Subjects and methods We recruited 46 adults (31 females; 15 males) and quantified anthropometrics, change in EE, and BAT thermogenesis after a cooling condition in the lab. A subsample of 21 participants wore temperature loggers for three days in order to quantify ambient temperature exposure. Results BAT thermogenesis was not significantly associated with change in EE. Participants that were exposed to lower average temperatures exhibited greater BAT thermogenesis (p = 0.013). Change in EE, however, was not significantly associated with time spent outside nor average temperature exposure. Conclusion Our study provides mixed evidence for the role of BAT thermogenesis in metabolic adaptations to cold stress among NYC residents. Many young adults in NYC are exposed to minimal amounts of cold stress, and this trend is likely to be exacerbated by climate change.

When the cold gets under your skin: Evidence for brown adipose tissue activity in Samoan adults

Article

Sep 2023

Objectives Brown adipose tissue (BAT) is a heat‐producing organ aiding nonshivering thermogenesis (NST) during cold stress. Due to its potential cold‐adaptive role BAT has been predominantly studied in cold and temperate climate populations, but not among warm‐climate adults. This work explores if BAT activity can be inferred in Samoans. Materials and Methods We inferred BAT activity by comparing metabolic rate and surface heat dissipation using indirect calorimetry and thermal imaging between room temperature and cold exposure among Samoans ( N = 61, females: n = 38) from ‘Upolu Island, Samoa. BAT activity was inferred using ANOVA linear regression models with the variables measured at cold exposure as outcomes. T ‐tests were used to compare changes in surface temperature between room temperature and cold exposure. Results Metabolic rate significantly increased after cooling. In both the supraclavicular area, a known BAT location, and the sternum, a non‐BAT location, temperatures decreased significantly upon cold exposure. Differences in supraclavicular temperatures between room temperature and cold were significantly smaller than differences in sternum temperatures between exposures. These results suggest that BAT thermogenesis occurred in known BAT‐locations and thus contributed to NST during cooling. Conclusions This study adds to our understanding of BAT activity across different populations and climates. Further study may illuminate whether the cold‐adaptive properties of BAT may have played a role in the successful expansion of populations across the globe, including warm‐climate groups.

Reproductive plasticity in Polistes paper wasp workers and the evolutionary origins of sociality

Article

Apr 2011

Regulatory pathways in solitary species provide the raw materials for the evolution of sociality. Therefore, comparing the mechanisms that mediate reproductive plasticity in social species and their solitary ancestors can provide insight into the evolutionary origin of sociality. In many solitary insects, the effect of juvenile hormone (JH) on fertility is mediated through the fat body; individuals in good physical condition show a stronger fertility response to JH than individuals in poor physical condition. Here, we test whether a similar, condition-dependent JH response mediates fertility in workers of the primitively eusocial Polistes dominulus wasps. We test how body weight, JH, and adult nutrition influence worker ovarian development. Both JH-treatment and adult nutrition dramatically increased ovarian development. Body weight also influenced ovarian development, as large workers developed more eggs than smaller workers. Body weight and fat are strongly linked in P. dominulus workers, so these results suggest that the fat-dependent JH responsiveness common in solitary insects is conserved in social wasps. The simple, ancestral relationship between reproductive investment and physical condition may facilitate cooperation by allowing workers to adaptively allocate energy into reproduction based on their probability of successfully becoming a queen.

Human Bodies in Extreme Environments

Article

Oct 2023
ANNU REV ANTHROPOL

Cara Ocobock

Human habitation and adaptation to extreme environments have a deep history in anthropological research. Anthropologists’ understanding of these ecological pressures and how humans respond to them has grown substantially over the last 100+ years. This review covers long-standing knowledge on adaptation to classic extreme conditions of heat, cold, and high altitude, while also updating the areas in which recent research has broadened our understanding of human adaptation, acclimatization, and resilience. Unfortunately, the intersecting stresses of structural inequality and climate change have made these extremes more extreme, with drastic negative impacts on health and well-being. Future research will need to explore how extreme environments, structural inequality, and climate change are embodied as well as mitigated so that humans are better prepared to face a rapidly changing world.

Between a rock and a cold place: Neanderthal biocultural cold adaptations

Article

Apr 2021

A large body of work focuses on the unique aspects of Neanderthal anatomy, inferred physiology, and behavior to test the assumption that Neanderthals were hyper‐adapted to living in cold environments. This research has expanded over the years to include previously unexplored and potentially adaptive features such as brown adipose tissue and fire‐usage. Here we review the current state of knowledge of Neanderthal cold adaptations along morphological, physiological, and behavioral lines. While highlighting foundational as well as recent work, we also emphasize key areas for future research. Despite thriving in a variety of climates, it is well‐accepted that Neanderthals appear to be the most cold‐adapted of known fossil hominin groups; however, there are still many unknowns. There is a great deal yet to be uncovered about the nature and manifestation of Neanderthal adaptation and how the synergy of biology and culture helped buffer them against extreme and variable environments.

A systematic review on the role of infrared thermography in the Brown adipose tissue assessment

Article

Full-text available

Mar 2020
REV ENDOCR METAB DIS

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.

Recent Research on the Human Biology of Pastoralists

Article

Sep 2024

Benjamin C Campbell

Despite encroachment by agricultural systems and globalization, pastoral nomads maintain a robust presence in terms of numbers and subsistence activity. At the same time, increasing concern about climate change has promoted awareness that increased climatic fluctuation may push pastoral population past their capacity for resilience. The response of pastoralists to climate change has important implications for our evolutionary past and our increasingly problematic future. Yet, pastoralists have received less explicit attention than foragers as populations under consistent selective constraints including limited caloric intake, high levels of habitual activity, and high disease burdens. Additional factors include exposure to cold and high temperatures, as well as high altitude. Over the last 20 or so years, the use of new techniques for measuring energetics, including actigraphs and doubly labeled water have built on existing noninvasive sample collection for hormones, immune markers and genes to provide a more detailed picture of the human biology of pastoral populations. Here I consider recent work on pastoralists from Siberia and northern Europe, Africa, Asia, and South America. I survey what is known about maternal milk composition and infant health, childhood growth, lactase persistence, and adult energy expenditure and lactase persistence to build a picture of the pastoralist biological response to environmental conditions, including heat, cold, and high altitude. Where available I include information about population history because of its importance for selection. I end by outlining the impact of milk consumption and climate over the human life cycle and make suggestions for further research.

Brown Adipose Tissue Activity and Childhood Exposure to Cold Are Associated With Hot Flashes at Menopause

Article

Sep 2024
AM J HUM BIOL

Objective Hot flashes (HFs) are experienced as sudden sensations of heat. We hypothesized that brown adipose tissue (BAT) activation could increase the likelihood of HFs in winter. The aim of this study was to test whether women with more BAT activity were more likely to experience self‐reported or biometrically measured HFs. Methods Women aged 45–55 years ( n = 270) participated in face‐to‐face interviews and anthropometric and ambulatory measures. Level of BAT activity was estimated from the difference in supraclavicular skin temperature measured by infrared thermography before and after cooling. Logistic regressions were applied to examine whether bothersome HFs (yes/no) during the past 2 weeks were associated with BAT activity, adjusting for menopausal status, childhood exposure to cold, waist/hip ratio, and self‐reported health. Linear regressions were used to examine the frequency of self‐reported and biometrically measured HFs during the study period and BAT activity, adjusting for potential confounders. Results Menopausal status, childhood exposure to cold, waist‐to‐hip ratio (WHR), and self‐reported health were associated with both BAT activity and HFs. After adjusting for potential confounders, an increase in BAT activity almost tripled the likelihood of bothersome HFs (OR 2.84, 95% CI 1.26–6.43). In linear regressions, BAT activity was not associated with frequency of subjective or objective HFs during the study period, but childhood exposure to cold was associated with subjective HF report ( β = 0.163, p = 0.010). Conclusion To our knowledge, this is the first study of BAT activation and HFs. Our results support a role for BAT activity in HF experience. Therefore, we encourage further examination of the role of BAT, as well as childhood exposure to cold, in HFs.

Adaptive Endocrine and Metabolic Effects

Chapter

Mar 2024

Giovanni Lombardi

This chapter describes the main metabolic and endocrine effects of whole-body cryotherapy (WBC) and more generally, of cold exposure. The ability to mount an adequate response to cold derives from the adaptive strategies developed by our ancestors and, mainly, Neanderthals. The genetic inheritance obtained from the past is particularly evident in specific traits expressed by contemporary populations living or acting in specific climate environments and face up to more or less extreme coldness. The physiologic responses mounted by the subjects belonging to these populations are the same experienced by non-habituated subjects who are exposed to WBC and similarly, chronic exposure causes adaptation. Changes in the metabolic usage of energy substrates represent an important response to cold exposure and, similarly to the analgesic and anti-inflammatory effects, are driven by the activation of the sympathetic nervous system. According to the first promising evidence, the possibility to modify the metabolic homeostasis through WBC would open relevant novel therapeutic options in the field of dysmetabolic conditions.

Tecido adiposo marrom: uma alternativa para manutenção de peso em pacientes com obesidade

Article

Full-text available

Nov 2023

Objetivo: Quantificar por meio de imagens termográficas a atividade do tecido adiposo marrom (TAM) através da ação do termogênico pimenta e protocolo frio em indivíduos com obesidade. Métodos: Nove voluntários com obesidade submetidos ao protocolo de ativação do TAM pelo frio e pelo uso de capsinóide, num estudo duplo cego. No primeiro dia, houve a uma coleta de imagem basal e, em seguida, foram submetidos ao protocolo frio e após o protocolo termogênico duplo-cego, com intervenção da cápsula. A coleta de imagens ocorreu durante 2h30. No segundo dia, foram registradas as imagens após a intervenção da cápsula por 2h30, conforme descrito no primeiro dia. As imagens foram analisadas pela média dos valores da escala cinza para verificação de alteração significativa. Resultados: Não houve ativação do TAM para o protocolo frio e placebo e houve ativação do TAM para protocolo de capsinóide. Discussão: A ativação do TAM foi relacionada aos tipos de receptores termossensoriais que são diferentes para o frio e para capsinóide e que sofrem influência com o ciclo circadiano, fatores ambientais e quantidade de tecido adiposo branco. Conclusão: Este estudo demonstrou a correlação dos hábitos e a composição corporal na ativação do TAM em obesidade.

Pearl Memorial Lecture. Humans at the extremes: Exploring human adaptation to ecological and social stressors

Article

Full-text available

Nov 2023
AM J HUM BIOL

William R. Leonard

The field of human biology has long explored how human populations have adapted to extreme environmental circumstances. Yet, it has become increasingly clear that conditions of social stress, poverty, and lifestyle change play equally important roles in shaping human biological variation and health. In this paper, I provide a brief background on the foundational human adaptability research of the International Biological Programme (IBP) from the 1960s, highlighting how its successes and critiques have shaped current research directions in the field. I then discuss and reflect on my own field research that has examined the influence of both environmental and social stresses on human populations living in different ecosystems: the Peruvian Andes, the Siberian arctic, and the Bolivian rainforest. Finally, I consider how the papers in this special issue advance our understanding of human adaptability to extreme conditions and offer directions for future research. Drawing on our field's distinctive evolutionary and biocultural perspectives, human biologists are uniquely positioned to examine how the interplay between social and ecological domains influences the human condition.

18F-FDG PET/CT technology for the assessment of brown adipose tissue: an updated review

Article

Nov 2023
EXPERT REV MED DEVIC

Introduction: This review provides an update of 18 F-fluorodeoxyglucose ([18F] FDG) for Brown adipose tissue (BAT) activity quantification, whose role is not completely understood. Areas covered: We conducted an unstructured search of the literature for any studies employing the [18F] FDG PET in BAT assessment. We explored BAT quantification both in healthy individuals and in different pathologies, after cold exposure and as a metabolic biomarker. The assessment of possible BAT modulators by using [18F] FDG PET is shown. Further PET tracers and novel developments for BAT assessments are also described. Expert opinion: Further PET tracers and imaging modalities are under investigation, but the [18F] FDG PET is currently the method of choice for the evaluation of BAT and further multicentric trials are needed for a better understanding of the BAT physiopathology, also after cold stimuli. The modulation of BAT activity, assessed by [18F] FDG PET imaging, seems a promising tool for the management of conditions such as obesity and type 2 diabetes. Moreover, an interesting possible correlation of BAT activation with prognostic [18F] FDG PET indices in cancer patients should be assessed with further multicentric trials.

Indication of mixed glucose and fatty acid use by inferred brown adipose tissue activity in Samoans

Article

Oct 2023

Objectives Despite the growing rates of global obesity and the known positive associations between brown adipose tissue (BAT) and cardiovascular health, little is known about the metabolic effects of BAT activity in Samoans, a population at high risk of obesity and type II diabetes. Here we assessed the potential effects of inferred BAT activity on metabolic health markers in Samoan adults exposed to mild cold. Methods Using point‐of‐care finger prick technology we measured fasting glucose, total cholesterol, high‐density lipoprotein (HDL), and low‐density lipoprotein (LDL) levels before and after 30 min of cold exposure among 61 individuals (38 females, 23 males, ages 31–54) from ‘Upolu Island, Samoa. Respiratory quotient was measured by indirect calorimetry to determine substrate metabolism at room temperature and cold exposure. Results Fasting glucose levels decreased significantly ( p < .001) after cold exposure while neither total cholesterol ( p = .88), HDL ( p = .312), nor LDL ( p = .089) changed. Respiratory quotient decreased significantly ( p = .009) between exposures, suggesting an increased preference for lipid metabolism as a response to cold. Conclusions The observed effects of inferred BAT activity on biomarkers suggest BAT activity utilizes both glucose and lipid‐derived fatty acids as fuel for thermogenesis. Our work provides evidence for the beneficial metabolic effects of BAT and emphasizes the need for the population‐specific development of metabolic treatments involving BAT to ensure the successful and equitable minimization of extreme consequences of obesity and metabolic health.

Human cold adaptation: An unfinished agenda v2.0

Article

Jun 2023
AM J HUM BIOL

Cara Ocobock

Background: Research on human extreme cold climate adaptations has benefitted from a recent resurgence since Ted Steegmann laid out his Human Cold Adaptation Agenda in 2007. Human biologists have drastically expanded our knowledge in this area during the last 15 years, but we still have a great deal more work to do to fulfill the cold climate adaptation agenda. Methods: Here, I follow Steegmann's example by providing a review of cold climate adaptations and setting forth a new, expanded agenda. Results: I review the foundational work on cold climate adaptations including classic Bergmann, Allen, and Thomson rules as well as early work assessing metabolic differences among Indigenous cold climate populations. From there, I discuss some of the groundbreaking work currently taking place on cold climate adaptations such as brown adipose tissue (a heat generating organ), physical activity levels, metabolic rates, and behavioral/cultural mechanisms. Finally, I present a path forward for future research with a focus on some of the basic extreme cold adaptations as well as how human biologists should approach the effects of climate change on human health and well-being, particularly within a cold climate context. Conclusion: The Arctic has felt the dramatic effects of climate change sooner and more acutely than other parts of the world, making it an ideal location for studying both cold climate adaptations and climate change resilience. Human biologists have a great deal to contribute to the conversation on not only adaptations to extreme cold, but also the ways in which climate change is being embodied by cold climate populations.

Feasibility of using infrared thermal imaging to examine brown adipose tissue in infants aged 18 to 25 months

Article

Nov 2021

Background Recent studies in adults indicate that cold-induced temperature change of supraclavicular skin corresponds with brown adipose tissue (BAT) thermogenesis. Aim This study examined the feasibility of using thermography to assess temperature changes in infants aged 18–25 months after mild cooling. Further, this study sought to evaluate whether cold exposure induces a thermal response suggestive of BAT activity underlying the supraclavicular region. Subjects and Methods Changes in maximum skin temperature at the supraclavicular and interscapular regions were determined using thermal imaging following a mild 5-minute cooling condition (by removal of clothes in a climate-controlled room) in 67 Samoan infants. Temperature changes of the forehead and hand, known BAT-free regions, served as indicators of cooling efficacy. Results Infants with increased hand and forehead temperatures after cold exposure were excluded from analysis, reducing the effective sample size to 19 infants. On average, forehead (p < 0.001), hand (p < 0.001) and back (0.029) temperatures dropped significantly while supraclavicular temperatures remained constant. Participants with greater decreases in forehead temperature tended to exhibit greater supraclavicular thermogenesis (p = 0.084), suggesting potential BAT activity in this region. Conclusions While further work is necessary to develop a reliable cooling condition, this study provides proof-of-concept for non-invasive assessment of BAT activity in infants.

Published papers on on thermology or temperature measurements, 2019-2021. Volume 6 B

Data

Full-text available

Apr 2022

Kurt Ammer

Volume 6B of an index of publications on thermology or temperature measurement 2019-2021, updated 15.04.2022

Programming mediated by fatty acids affects uncoupling protein 1 (UCP-1) in brown adipose tissue

Article

Full-text available

Sep 2018

Brown adipose tissue (BAT) has recently been given more attention for the part it plays in obesity. BAT can generate great amounts of heat through thermogenesis by the activation of uncoupling protein 1 (UCP-1), which can be regulated by many environmental factors such as diet. Moreover, the build-up of BAT relates to maternal nutritional changes during pregnancy and lactation. However, at present, there is a limited number of studies looking at maternal nutrition and BAT development, and it seems that the research trend in this field has been considerably declining since the 1980s. There is much to discover yet about the role of different fatty acids on the development of BAT and the activation of UCP-1 during the fetal and the postnatal periods of life. A better understanding of the impact of nutritional intervention on the epigenetic regulation of BAT could lead to new preventive care for metabolic diseases such as obesity. It is important to know in which circumstances lipids could programme BAT during pregnancy and lactation. The modification of maternal dietary fatty acids, amount and composition, during pregnancy and lactation might be a promising strategy for the prevention of obesity in the offspring and future generations.

Looking on the “brite” side exercise-induced browning of white adipose tissue

Article

Full-text available

Mar 2019
PFLUG ARCH EUR J PHY

The need for effective and convenient ways of combatting obesity has created great interest in brown adipose tissue (BAT). However, because adult humans have relatively little amounts of BAT, the possibility of browning white adipose tissue (WAT), i.e., switching the metabolism of WAT from an energy storing to energy burning organ, has gained considerable attention. Exercise has countless health benefits, and has consistently been shown to cause browning in rodent white adipose tissue. The purpose of this review is to provide an overview of recent studies examining the effects of exercise and other interventions on the browning of white adipose tissue. The role of various endocrine factors, including catecholamines, interleukin-6, irisin, and meteorin-like in addition to local re-esterification-mediated mechanisms in inducing the browning of WAT will be discussed. The physiological importance of browning will be discussed, as will discrepancies in the literature between human and rodent studies.

Skin temperature response to a liquid meal intake is different in men than in women

Article

Full-text available

Jun 2018
CLIN NUTR

Background & aim: The thermic effect of food (TEF) refers to the increase of the metabolic rate and body temperature in response to a single meal. To date, most of the studies have focused to determine the TEF in terms of energy expenditure, but little is known about which is the response in terms of skin temperature. The aim of this study was to analyze whether the thermic effect of food (TEF) on the skin temperature with a standardized and individualized liquid meal test is different in young adult men than in young adult women. Methods: A total of 104 young adults (36 men and 68 women, age: 18-25 years old) consumed a standardized and individualized liquid meal (energy intake: 50% of measured basal metabolic rate, 50% carbohydrates, 35% fat, 15% protein). The skin temperature was measured by means of 17 iButtons during 3 h and 20 min. The mean, proximal, distal, and supraclavicular skin temperature, as well as the peripheral gradient, were determined as a proxy of a peripheral vasoconstriction. The participants reported the thermal sensation of the whole body, clavicular, feet, and hands zones. The body composition was measured by dual X-ray absorptiometry. Results: The overall, mean, proximal, and supraclavicular skin temperature significantly increased after the meal intake (all P < 0.05 vs. the baseline temperature). There was a postprandial peripheral vasoconstriction right after the meal intake and over the first hour and a peripheral vasodilatation during the second and third hour. Women had a higher increase in all skin temperature parameters in comparison to men (all, P < 0.05), whereas there were no sex differences in the proximal skin temperature (P = 0.279). The pattern of thermal sensation was similar between sexes, but women always felt colder than men. All of the results persisted after adjusting the analyses for body composition or menstrual cycle. Conclusion: A standardized and individualized liquid meal test increases the skin temperature in young adults, being the thermic effect higher in women than in men.

Substantial Metabolic Activity of Human Brown Adipose Tissue during Warm Conditions and Cold-Induced Lipolysis of Local Triglycerides

Article

Full-text available

May 2018
CELL METAB

Current understanding of in vivo human brown adipose tissue (BAT) physiology is limited by a reliance on positron emission tomography (PET)/computed tomography (CT) scanning, which has measured exogenous glucose and fatty acid uptake but not quantified endogenous substrate utilization by BAT. Six lean, healthy men underwent ¹⁸fluorodeoxyglucose-PET/CT scanning to localize BAT so microdialysis catheters could be inserted in supraclavicular BAT under CT guidance and in abdominal subcutaneous white adipose tissue (WAT). Arterial and dialysate samples were collected during warm (∼25°C) and cold exposure (∼17°C), and blood flow was measured by ¹³³xenon washout. During warm conditions, there was increased glucose uptake and lactate release and decreased glycerol release by BAT compared with WAT. Cold exposure increased blood flow, glycerol release, and glucose and glutamate uptake only by BAT. This novel use of microdialysis reveals that human BAT is metabolically active during warm conditions. BAT activation substantially increases local lipolysis but also utilization of other substrates such as glutamate. Weir et al., using microdialysis, have shown that human brown adipose tissue (BAT) is metabolically active in warm conditions, with higher glucose uptake and lactate release than white AT. Cold activation increased glucose and glutamate uptake and glycerol release by BAT, quantifying substrate utilization and hydrolysis of BAT triglycerides during thermogenesis.

Seasonal differences in brown adipose tissue density and pulse rate variability in a thermoneutral environment

Article

Full-text available

Feb 2018
J Physiol Anthropol

Background Brown adipose tissue (BAT) is sympathetically activated and induces thermogenesis during cold exposure, thereby influencing energy expenditure and body fat levels. The very low frequency (VLF) components of pulse rate variability could be a form of thermogenic sympathetic nervous activity, but no clear relationship has yet been reported between VLF activity and BAT density. We therefore aimed to evaluate the association between them. Methods We enrolled 20 adults in winter and 20 matched adults in summer. We assessed BAT densities based on total hemoglobin concentrations ([total-Hb]) measured with near-infrared time-resolved spectroscopy. We calculated VLF activity from pulse rate variability measurements. ResultsBAT density ([total-Hb]; winter 70.5 ± 17.0 μM, summer 57.8 ± 18.3 μM) and VLF activity (winter 6.7 ± 0.8, summer 6.1 ± 0.9) were significantly higher in winter than in summer (P < 0.05). However, there was no significant correlation between VLF activity and BAT density in either season. Conclusion Each parameter exhibited seasonal variation, but we failed to observe any significant correlations.

A New Personalized Cooling Protocol to Activate Brown Adipose Tissue in Young Adults

Article

Full-text available

Nov 2017

Brown adipose tissue (BAT) activity is induced when humans are exposed to cold. Therefore, cold exposure prior to the ¹⁸F-FDG-PET/CT scan is used as a tool to quantify BAT. Several cooling protocols, including fixed and personalized ones are currently in use. The aim of the present study was to determine the effect of a new personalized cooling protocol where the shivering threshold was measured on a separate day, on BAT volume and activity in young adults. A total of 47 adults (n = 28 women) aged 22 ± 2 years participated in the study. We determined participants' shivering threshold (visually and self-reported) using a water perfused cooling vest in an air-conditioned cold room. 48–72 h later, participants wore the cooling vest set at ~4°C above the shivering threshold for 60 min prior to injection of ¹⁸F-FDG and ~5°C above the shivering threshold for ~60 min after injection, until PET/CT scan. We quantified BAT following BARCIST 1.0 recommendations. We identified 40 participants (85%, n = 25 women) as PET+ and 7 (n = 3 women) as PET–. The PET+ group presented significantly higher BAT volume and activity than PET– group (all P < 0.05). PET+ women had higher BAT mean activity than PET+ men (SUVmean: 5.0 ± 1.6 vs. 3.6 ± 0.9 g/ml respectively, P = 0.003), and there were no significant sex differences in BAT volume (P = 0.161). A total of 9 out of 47 participants did not shiver during the shivering threshold test. Our findings are similar to previous cold-stimulated human BAT studies; therefore, we conclude that our personalized cooling protocol is able to activate BAT in young adults.

Differences between the most used equations in BAT-human studies to estimate parameters of skin temperature in young lean men

Article

Full-text available

Dec 2017

Cold exposure is necessary to activate human brown adipose tissue (BAT), resulting in heat production. Skin temperature is an indirect measure to monitor the body’s reaction to cold. The aim of this research was to study whether the most used equations to estimate parameters of skin temperature in BAT-human studies measure the same values of temperature in young lean men (n = 11: 23.4 ± 0.5 years, fat mass: 19.9 ± 1.2%). Skin temperature was measured with 26 ibuttons at 1-minute intervals in warm and cold room conditions. We used 12 equations to estimate parameters of mean, proximal, and distal skin temperature as well as skin temperature gradients. Data were analysed with Temperatus software. Significant differences were found across equations to measure the same parameters of skin temperature in warm and cold room conditions, hampering comparison across studies. Based on these findings, we suggest to use a set of 14 ibuttons at anatomical positions reported by ISO STANDARD 9886:2004 plus five ibuttons placed on the right supraclavicular fossa, right middle clavicular bone, right middle upper forearm, right top of forefinger, and right upper chest.

Brown Adipose Reporting Criteria in Imaging STudies (BARCIST 1.0): Recommendations for Standardized FDG-PET/CT Experiments in Humans

Article

Full-text available

Aug 2016

Human brown adipose tissue (BAT) presence, metabolic activity, and estimated mass are typically measured by imaging [18F]fluorodeoxyglucose (FDG) uptake in response to cold exposure in regions of the body expected to contain BAT, using positron emission tomography combined with X-ray computed tomography (FDG-PET/CT). Efforts to describe the epidemiology and biology of human BAT are hampered by diverse experimental practices, making it difficult to directly compare results among laboratories. An expert panel was assembled by the National Institute of Diabetes and Digestive and Kidney Diseases on November 4, 2014 to discuss minimal requirements for conducting FDG-PET/CT experiments of human BAT, data analysis, and publication of results. This resulted in Brown Adipose Reporting Criteria in Imaging STudies (BARCIST 1.0). Since there are no fully validated best practices at this time, panel recommendations are meant to enhance comparability across experiments, but not to constrain experimental design or the questions that can be asked.

A new method of infrared thermography for quantification of brown adipose tissue activation in healthy adults (TACTICAL): a randomized trial

Article

Full-text available

Jul 2016

The ability to alter the amount and activity of brown adipose tissue (BAT) in human adults is a potential strategy to manage obesity and related metabolic disorders associated with food, drug, and environmental stimuli with BAT activating/recruiting capacity. Infrared thermography (IRT) provides a non-invasive and inexpensive alternative to the current methods (e.g. ¹⁸F-FDG PET) used to assess BAT. We have quantified BAT activation in the cervical-supraclavicular (C-SCV) region using IRT video imaging and a novel image computational algorithm by studying C-SCV heat production in healthy young men after cold stimulation and the ingestion of capsinoids in a prospective double-blind placebo-controlled randomized trial. Subjects were divided into low-BAT and high-BAT groups based on changes in IR emissions in the C-SCV region induced by cold. The high-BAT group showed significant increases in energy expenditure, fat oxidation, and heat output in the C-SCV region post-capsinoid ingestion compared to post-placebo ingestion, but the low-BAT group did not. Based on these results, we conclude that IRT is a promising tool for quantifying BAT activity. Electronic supplementary material The online version of this article (doi:10.1007/s12576-016-0472-1) contains supplementary material, which is available to authorized users.

Brown adipose tissue is involved in diet-induced thermogenesis and whole-body fat utilization in healthy humans

Article

Full-text available

Jul 2016

Background/objectives: Brown adipose tissue (BAT) is a potential therapeutic target against obesity and diabetes through thermogenesis and substrate disposal with cold exposure. The role of BAT in energy metabolism under thermoneutral conditions, however, remains controversial. We assessed the contribution of BAT to energy expenditure (EE), particularly diet-induced thermogenesis (DIT), and substrate utilization in human adults. Methods: In this cross-sectional study, BAT activity was evaluated in 21 men using (18)F-fluoro-2-deoxy-D-glucose positron emission tomography combined with computed tomography ((18)F-FDG-PET/CT) after cold exposure (19 °C). The subjects were divided into BAT-positive (n=13) and BAT-negative (n=8) groups according to the (18)F-FDG-PET/CT findings. Twenty-four hour EE, DIT, and respiratory quotient were measured using a whole-room indirect calorimeter at 27 °C. Results: Body composition, blood metabolites, and 24-h EE did not differ between groups. DIT (%), calculated as DIT divided by total energy intake, however, was significantly higher in the BAT-positive group (BAT-positive: 9.7±2.5%, BAT-negative: 6.5±4.0%, P=0.03). The 24-h respiratory quotient was significantly lower (P=0.03) in the BAT-positive group (0.860±0.028) than in the BAT-negative group (0.889±0.024). Conclusion: DIT and fat utilization were higher in BAT-positive subjects compared to BAT-negative subjects, suggesting that BAT has a physiologic role in energy metabolism.International Journal of Obesity accepted article preview online, 19 July 2016. doi:10.1038/ijo.2016.124.

Glucocorticoids Acutely Increase Brown Adipose Tissue Activity in Humans, Revealing Species-Specific Differences in UCP-1 Regulation

Article

Full-text available

Jul 2016
CELL METAB

The discovery of brown adipose tissue (BAT) in adult humans presents a new therapeutic target for metabolic disease; however, little is known about the regulation of human BAT. Chronic glucocorticoid excess causes obesity in humans, and glucocorticoids suppress BAT activation in rodents. We tested whether glucocorticoids regulate BAT activity in humans. In vivo, the glucocorticoid prednisolone acutely increased 18fluorodeoxyglucose uptake by BAT (measured using PET/CT) in lean healthy men during mild cold exposure (16°C–17°C). In addition, prednisolone increased supraclavicular skin temperature (measured using infrared thermography) and energy expenditure during cold, but not warm, exposure in lean subjects. In vitro, glucocorticoids increased isoprenaline-stimulated respiration and UCP-1 in human primary brown adipocytes, but substantially decreased isoprenaline-stimulated respiration and UCP-1 in primary murine brown and beige adipocytes. The highly species-specific regulation of BAT function by glucocorticoids may have important implications for the translation of novel treatments to activate BAT to improve metabolic health.

Brown Adipose Tissue Is Linked to a Distinct Thermoregulatory Response to Mild Cold in People

Article

Full-text available

Apr 2016

Brown adipose tissue (BAT) plays an important role in thermoregulation in rodents. Its role in temperature homeostasis in people is less studied. To this end, we recruited 18 men [8 subjects with no/minimal BAT activity (BAT−) and 10 with pronounced BAT activity (BAT+)]. Each volunteer participated in a 6 h, individualized, non-shivering cold exposure protocol. BAT was quantified using positron emission tomography/computed tomography. Body core and skin temperatures were measured using a telemetric pill and wireless thermistors, respectively. Core body temperature decreased during cold exposure in the BAT− group only (−0.34°C, 95% CI: −0.6 to −0.1, p = 0.03), while the cold-induced change in core temperature was significantly different between BAT+ and BAT− subjects (BAT+ vs. BAT−, 0.43°C, 95% CI: 0.20–0.65, p = 0.0014). BAT volume was associated with the cold-induced change in core temperature (p = 0.01) even after adjustment for age and adiposity. Compared to the BAT− group, BAT+ subjects tolerated a lower ambient temperature (BAT−: 20.6 ± 0.3°C vs. BAT+: 19.8 ± 0.3°C, p = 0.035) without shivering. The cold-induced change in core temperature (r = 0.79, p = 0.001) and supraclavicular temperature (r = 0.58, p = 0.014) correlated with BAT volume, suggesting that these non-invasive measures can be potentially used as surrogate markers of BAT when other methods to detect BAT are not available or their use is not warranted. These results demonstrate a physiologically significant role for BAT in thermoregulation in people. This trial has been registered with Clinaltrials.gov: NCT01791114 (https://clinicaltrials.gov/ct2/show/NCT01791114).

Human brown adipose tissue [15O]O2 PET imaging in the presence and absence of cold stimulus

Article

Full-text available

Sep 2016
EUR J NUCL MED MOL I

Purpose: Brown adipose tissue (BAT) is considered a potential target for combatting obesity, as it produces heat instead of ATP in cellular respiration due to uncoupling protein-1 (UCP-1) in mitochondria. However, BAT-specific thermogenic capacity, in comparison to whole-body thermogenesis during cold stimulus, is still controversial. In our present study, we aimed to determine human BAT oxygen consumption with [(15)O]O2 positron emission tomography (PET) imaging. Further, we explored whether BAT-specific energy expenditure (EE) is associated with BAT blood flow, non-esterified fatty acid (NEFA) uptake, and whole-body EE. Methods: Seven healthy study subjects were studied at two different scanning sessions, 1) at room temperature (RT) and 2) with acute cold exposure. Radiotracers [(15)O]O2, [(15)O]H2O, and [(18)F]FTHA were given for the measurements of BAT oxygen consumption, blood flow, and NEFA uptake, respectively, with PET-CT. Indirect calorimetry was performed to assess differences in whole-body EE between RT and cold. Results: BAT-specific EE and oxygen consumption was higher during cold stimulus (approx. 50 %); similarly, whole-body EE was higher during cold stimulus (range 2-47 %). However, there was no association in BAT-specific EE and whole-body EE. BAT-specific EE was found to be a minor contributor in cold induced whole-body thermogenesis (almost 1 % of total whole-body elevation in EE). Certain deep muscles in the cervico-thoracic region made a major contribution to this cold-induced thermogenesis (CIT) without any visual signs or individual perception of shivering. Moreover, BAT-specific EE associated with BAT blood flow and NEFA uptake both at RT and during cold stimulus. Conclusion: Our study suggests that BAT is a minor and deep muscles are a major contributor to CIT. In BAT, both in RT and during cold, cellular respiration is linked with circulatory NEFA uptake.

Is It Possible to Detect Activated Brown Adipose Tissue in Humans Using Single-Time-Point Infrared Thermography under Thermoneutral Conditions? Impact of BMI and Subcutaneous Adipose Tissue Thickness

Article

Full-text available

Mar 2016
PLOS ONE

Purpose To evaluate the feasibility to detect activated brown adipose tissue (BAT) using single-time-point infrared thermography of the supraclavicular skin region under thermoneutral conditions. To this end, infrared thermography was compared with 18-F-FDG PET, the current reference standard for the detection of activated BAT. Methods 120 patients were enrolled in this study. After exclusion of 18 patients, 102 patients (44 female, 58 male, mean age 58±17 years) were included for final analysis. All patients underwent a clinically indicated 18F-FDG-PET/CT examination. Immediately prior to tracer injection skin temperatures of the supraclavicular, presternal and jugular regions were measured using spatially resolved infrared thermography at room temperature. The presence of activated BAT was determined in PET by typical FDG uptake within the supraclavicular adipose tissue compartments. Local thickness of supraclavicular subcutaneous adipose tissue (SCAT) was measured on CT. Measured skin temperatures were statistically correlated with the presence of activated BAT and anthropometric data. Results Activated BAT was detected in 9 of 102 patients (8.8%). Local skin temperature of the supraclavicular region was significantly higher in individuals with active BAT compared to individuals without active BAT. However, after statistical correction for the influence of BMI, no predictive value of activated BAT on skin temperature of the supraclavicular region could be observed. Supraclavicular skin temperature was significantly negatively correlated with supraclavicular SCAT thickness. Conclusion We conclude that supraclavicular SCAT thickness influences supraclavicular skin temperature and thus makes a specific detection of activated BAT using single-time-point thermography difficult. Further studies are necessary to evaluate the possibility of BAT detection using alternative thermographic methods, e.g. dynamic thermography or MR-based thermometry taking into account BMI as a confounding factor.

Anatomical Grading for Metabolic Activity of Brown Adipose Tissue

Article

Full-text available

Feb 2016
PLOS ONE

Background Recent advances in obesity research suggest that BAT activity, or absence thereof, may be an important factor in the growing epidemic of obesity and its manifold complications. It is thus important to assess larger populations for BAT-activating and deactivating factors. ¹⁸FDG-PET/CT is the standard method to detect and quantify metabolic BAT activity, however, the manual measurement is not suitable for large studies due to its time-consuming nature and poor reproducibility across different software and devices. Methodology/Main Findings In a retrospective study, 1060 consecutive scans of 1031 patients receiving a diagnostic ¹⁸FDG-PET/CT were examined for the presence of active BAT. Patients were classified according to a 3-tier system (supraclavicular, mediastinal, infradiaphragmatic) depending on the anatomical location of their active BAT depots, with the most caudal location being the decisive factor. The metabolic parameters (maximum activity, total volume and total glycolysis) were measured on a standard PET/CT workstation. Mean age of the population was 60±14.6y. 41.61% of patients were female. Metabolically active BAT was found in 53 patients (5.1%). Female, younger and leaner patients tended to have more active BAT, higher metabolic activity and more caudally active BAT. In total, 15 patients showed only supraclavicular, 27 additional mediastinal, and 11 infradiaphragmal activity. Interestingly, the activation of BAT always followed a cranio-caudal gradient. This anatomical pattern correlated with age and BMI as well as with all metabolic parameters, including maximum and total glycolysis (p<0.001). Conclusion Based on our data we propose a simple method to grade or quantify the degree of BAT amount/activity in patients based on the most caudally activated depot. As new modalities for BAT visualization may arise in the future, this system would allow direct comparability with other modalities, in contrary to the PET-metrics, which are restricted to ¹⁸FDG-PET/CT.

Cold acclimation and health: Effect on brown fat, energetics, and insulin sensitivity

Article

Full-text available

Sep 2015

Brown adipose tissue (BAT) has emerged as a potential target in the treatment and prevention of obesity and type 2 diabetes. We have recently shown that a 10-day cold acclimation period leads to recruitment of BAT in young, lean humans. In addition, rodent studies have shown that prolonged cold exposure and increased BAT volume are associated with improvements in glucose homeostasis and insulin sensitivity. Here, we investigated the effect of cold-acclimation on BAT activity, energy metabolism, and whole-body insulin sensitivity in healthy lean subjects, obese subjects and type 2 diabetic (T2D) patients.

Supraclavicular skin temperature and BAT activity in lean healthy adults

Article

Full-text available

Sep 2015

The 'gold standard' for measuring brown adipose tissue (BAT) in humans is [(18)F]FDG-PET/CT-imaging. With this technique subjects are exposed to ionizing radiation and are therefore limited in the number of scans that can be performed. We investigated the relation between supraclavicular skin temperatures and BAT activity values using a strictly temperature-controlled air-cooling protocol. Data of 36 male subjects was analyzed. BAT activity was evaluated by [(18)F]FDG-PET/CT-imaging and skin temperature was measured by means of wireless temperature sensors. Supraclavicular skin temperature dropped less compared to skin temperatures at other sites (all P values <0.01). A significant positive correlation was found between the change in supraclavicular skin temperature with BAT activity (R (2) 0.23), and the change in supraclavicular skin temperature and non-shivering thermogenesis (R (2) 0.18, both P values <0.01). The correlations indicate that supraclavicular skin temperature (changes) can potentially be used as a qualitative measure of BAT activity and BAT thermogenesis.

Dermal White Adipose Tissue: A New Component of the Thermogenic Response

Article

Full-text available

Sep 2015

Recent literature suggests that the layer of adipocytes embedded in the skin below the dermis is far from being an inert spacer material. Instead, this layer of dermal white adipose tissue (dWAT) is a regulated lipid layer that comprises a crucial environmental defense. Amongst all the classes of biological molecules, lipids have the lowest thermal conductance and highest insulation potential. This property can be exploited by mammals to reduce heat loss, suppress brown adipose tissue activation, reduce the activation of thermogenic programs, and increase metabolic efficiency. Furthermore, this layer responds to bacterial challenge to provide a physical barrier and anti-microbial disinfection, and its expansion supports the growth of hair follicles and regenerating skin. In sum, this dWAT layer is a key defensive player with remarkable potential for modifying systemic metabolism, immune function and physiology. In this review, we discuss the key literature illustrating the properties of this recently recognized adipose depot.

Short-term cold acclimation improves insulin sensitivity in patients with type 2 diabetes mellitus

Article

Full-text available

Jul 2015
NAT MED

Cold exposure may be a potential therapy for diabetes by increasing brown adipose tissue (BAT) mass and activity. Here we report that 10 d of cold acclimation (14-15 °C) increased peripheral insulin sensitivity by ∼43% in eight type 2 diabetes subjects. Basal skeletal muscle GLUT4 translocation markedly increased, without effects on insulin signaling or AMP-activated protein kinase (AMPK) activation and only a minor increase in BAT glucose uptake.

Imaging human brown adipose tissue under room temperature conditions with 11C-MRB, a selective norepinephrine transporter PET ligand

Article

Full-text available

Mar 2015

Introduction: Brown adipose tissue (BAT) plays a critical role in adaptive thermogenesis and is tightly regulated by the sympathetic nervous system (SNS). However, current BAT imaging modalities require cold stimulation and are often unreliable to detect BAT in the basal state, at room temperature (RT). We have shown previously that BAT can be detected in rodents under both RT and cold conditions with (11)C-MRB ((S,S)-(11)C-O-methylreboxetine), a highly selective ligand for the norepinephrine transporter (NET). Here, we evaluate this novel approach for BAT detection in adult humans under RT conditions. Methods: Ten healthy, Caucasian subjects (5 M: age 24.6±2.6, BMI 21.6±2.7kg/m(2); 5 F: age 25.4±2.1, BMI 22.1±1.0kg/m(2)) underwent (11)C-MRB PET-CT imaging for cervical/supraclavicular BAT under RT and cold-stimulated conditions (RPCM Cool vest; enthalpy 15°C) compared to (18)F-FDG PET-CT imaging. Uptake of (11)C-MRB, was quantified as the distribution volume ratio (DVR) using the occipital cortex as a low NET density reference region. Total body fat and lean body mass were assessed via bioelectrical impedance analysis. Results: As expected, (18)F-FDG uptake in BAT was difficult to identify at RT but easily detected with cold stimulation (p=0.01). In contrast, BAT (11)C-MRB uptake (also normalized for muscle) was equally evident under both RT and cold conditions (BAT DVR: RT 1.0±0.3 vs. cold 1.1±0.3, p=0.31; BAT/muscle DVR: RT 2.3±0.7 vs. cold 2.5±0.5, p=0.61). Importantly, BAT DVR and BAT/muscle DVR of (11)C-MRB at RT correlated positively with core body temperature (r=0.76, p=0.05 and r=0.92, p=0.004, respectively), a relationship not observed with (18)F-FDG (p=0.63). Furthermore, there were gender differences in (11)C-MRB uptake in response to cold (p=0.03), which reflected significant differences in the change in (11)C-MRB as a function of both body composition and body temperature. Conclusions: Unlike (18)F-FDG, the uptake of (11)C-MRB in BAT offers a unique opportunity to investigate the role of BAT in humans under basal, room temperature conditions.

Classification of factors influencing the use of infrared thermography in humans: A review

Article

Full-text available

Mar 2015
INFRARED PHYS TECHN

Body temperature is one of the most commonly used indicators of health status in humans. Infrared thermography (IRT) is a safe, non-invasive and low-cost technique that allows for the rapid and non-invasive recording of radiating energy that is released from the body. IRT measures this radiation, directly related to Skin Temperature (Tsk) and has been widely used since the early 1960s in different areas. Recent technical advances in infrared cameras have made new human applications of IRT (beyond diagnostic techniques) possible. This review focuses on the lack of comprehensive information about the factors influencing the use of IRT in humans, and proposes a comprehensive classification in three primary groups: environmental, individual and technical factors. We aim: to propose a common framework for further investigations; to reinforce the accuracy of human IRT; to summarise and discuss the results from the studies carried out on each factor and to identify areas requiring further research to determine their effects on human IRT.

Infrared thermography in the detection of brown adipose tissue in humans

Article

Full-text available

Nov 2014

PET-CT using 18F-FDG is employed for detecting brown adipose tissue (BAT) in humans. Alternative methods are needed because of the radiation and cost of PET-CT imaging. The aim was to evaluate the accuracy of infrared thermography (IRT) in detecting human BAT benchmarked to PET-CT imaging. Seventeen individuals underwent a total of 29 PET-CT scans, 12 of whom were studied twice, after 2 h of cold stimulation at 19°C, in parallel with measurement of skin temperatures overlying the supraclavicular (SCV) fossa and the lateral upper chest (control), before and after cold stimulation. Of the 29 scans, 20 were BAT positive after cold stimulation. The mean left SCV temperature tended to be higher in the BAT-positive group before and during cooling. It was significantly higher (P = 0.04) than the temperature of the control area, which fell significantly during cooling in the BAT-positive (−1.2 ± 0.3°C, P = 0.002) but not in the negative (−0.2 ± 0.4°C) group. The temperature difference (Δtemp) between left SCV and chest increased during cooling in the BAT-positive (1.2 ± 0.2 to 2.0 ± 0.3°C, P < 0.002) but not in the negative group (0.6 ± 0.1 to 0.7 ± 0.1°C). A Δtemp of 0.9°C conferred a positive predictive value of 85% for SCV BAT, superior to that of SCV temperature. The findings were similar on the right. In conclusion, the Δtemp is significantly and consistently greater in BAT-positive subjects. The Δtemp quantified by IRT after 2-h cooling shows promise as a noninvasive convenient technique for studying SCV BAT function.

Supraclavicular Skin Temperature as a Measure of 18F-FDG Uptake by BAT in Human Subjects

Article

Full-text available

Jun 2014
PLOS ONE

Background: Brown adipose tissue (BAT) has emerged as a novel player in energy homeostasis in humans and is considered a potential new target for combating obesity and related diseases. The current 'gold standard' for quantification of BAT volume and activity is cold-induced 18F-FDG uptake in BAT. However, use of this technique is limited by cost and radiation exposure. Given the fact that BAT is a thermogenic tissue, mainly located in the supraclavicular region, the aim of the current study was to investigate whether cold-induced supraclavicular skin temperature and core body temperature may be alternative markers of BAT activation in humans. Subjects/methods: BAT volume and activity were measured in 24 healthy lean adolescent males (mean age 24.1±0.8 years), using cold-induced 18F-FDG uptake with PET-CT. Core body temperature was measured continuously in the small intestine with use of an ingestible telemetric capsule and skin temperature was measured by eighteen wireless iButtons attached to the skin following ISO-defined locations. Results: Proximal and distal (hand/feet) skin temperatures markedly decreased upon cold exposure, while supraclavicular skin temperature significantly increased (35.2±0.1 vs. 35.5±0.1°C, p = 0.001). Furthermore, cold-induced supraclavicular skin temperature positively correlated with both total (R2 = 0.28, P = 0.010) and clavicular BAT volume (R2 = 0.20, P = 0.030) and clavicular SUVmax (R2 = 0.27, P = 0.010), while core body temperature did not. Conclusions: Supraclavicular skin temperature as measured by iButtons may have predictive value for BAT detection in adult humans. This is highly desirable considering the increasing interest in pharmacological interventions to stimulate BAT in human subjects. Trial registration: NTR 2473.

Brown adipose tissue, energy expenditure, and biomarkers of cardio-metabolic health among the Yakut (Sakha) of northeastern Siberia

Article

Oct 2018

Objectives This study provides the first investigation of non‐shivering thermogenesis (NST) and brown adipose tissue (BAT) activity among an indigenous circumpolar population, the Yakut of northeastern Siberia. The study also examines the health significance of BAT activity in this population by testing the relationships between BAT thermogenesis and biomarkers of cardio‐metabolic disease risk, such as percent body fat and blood glucose and cholesterol levels. Methods Data were collected in the Sakha Republic (Yakutia) for 31 men and 43 women. Change in energy expenditure and BAT thermogenesis were quantified after a 30‐minute mild cooling condition. Anthropometric dimensions, blood glucose, and lipid levels were also collected. Results On average, the skin temperature of the supraclavicular area was constant after cooling while the skin temperature of a point on the sternum dropped significantly (P < .001), thus suggesting the presence of active supraclavicular BAT among Yakut adults. Participants with evidence of greater BAT thermogenesis exhibited a larger percent change in energy expenditure (% ΔEE) and an increase in respiratory quotient (RQ) after cooling (P ≤ .05). While there was no relationship between BAT activity and blood lipid levels, BAT thermogenesis was positively associated with blood glucose levels (P < .01). Conclusions Yakut adults exhibit evidence of active BAT deposits. Given that there is a significant relationship between BAT activity and % ΔEE, it is possible that BAT plays a role in NST among Yakut adults. While the relationship between BAT and body composition is inconclusive, participants with greater BAT seemed to preferentially utilize glucose during cold stress exposure.

Maternal n-3 PUFA supplementation promotes fetal brown adipose tissue development through epigenetic modifications in C57BL/6 mice

Article

Sep 2018
BBA-MOL CELL BIOL L

Abstract Brown adipose tissue (BAT) is a crucial regulator of energy expenditure. Emerging evidence suggests that n-3 PUFA potentiate brown adipogenesis in vitro. Since the pregnancy and lactation is a critical time for brown fat formation, we hypothesized that maternal supplementation of n-3 PUFA promotes BAT development in offspring. Female C57BL/6 mice were fed a diet containing n-3 PUFA (3%) derived from fish oil (FO), or an isocaloric diet devoid of n-3 PUFA (Cont) during pregnancy and lactation. Maternal n-3 PUFA intake was delivered to the BAT of neonates significantly reducing the n-6/n-3 ratio. The maternal n-3 PUFA exposure was linked with upregulated brown-specific gene and protein profiles and the functional cluster of brown-specific miRNAs. In addition, maternal n-3 PUFA induced histone modifications in the BAT evidenced by 1) increased epigenetic signature of brown adipogenesis, i.e., H3K27Ac and H3K9me2, 2) modified chromatin-remodeling enzymes, and 3) enriched the H3K27Ac in the promoter region of Ucp1. The offspring received maternal n-3 PUFA nutrition exhibited a significant increase in whole-body energy expenditure and better maintenance of core body temperature against acute cold treatment. Collectively, our results suggest that maternal n-3 PUFA supplementation potentiates fetal BAT development via the synergistic action of miRNA production and histone modifications, which may confer long-lasting metabolic benefits to offspring.

Estimation of non-shivering thermogenesis and cold-induced nutrient oxidation rates: Impact of method for data selection and analysis

Article

Sep 2018
CLIN NUTR

Background & aims: Since the discovery of active brown adipose tissue in human adults, non-shivering cold-induced thermogenesis (CIT) has been regarded as a promising tool to combat obesity. However, there is a lack of consensus regarding the method of choice to analyze indirect calorimetry data from a CIT study. We analyzed the impact of methods for data selection and methods for data analysis on measures of cold-induced energy expenditure (EE) and nutrient oxidation rates. Methods: Forty-four young healthy adults (22.1 ± 2.1 years old, 25.6 ± 5.2 kg/m2, 29 women) participated in the study. Resting metabolic rate (RMR), cold-induced thermogenesis (CIT), and cold-induced nutrient oxidation rates were estimated by indirect calorimetry under fasting conditions during 1 h of cold exposure combining air conditioning (19.5-20 °C) and a water perfused cooling vest set at a temperature of 4 °C above the individual shivering threshold. We applied three methods for data selection: (i) time intervals every 5 min (5min-TI), (ii) the most stable 5-min period of every forth part of the cold exposure (5min-SS-4P), and (iii) the most stable 5-min period of every half part of the cold exposure (5min-SS-2P). Lately we applied two methods for data analysis: (i) area under the curve as a percentage of the baseline RMR (AUC) and; (ii) the difference between EE at the end of the cold exposure and baseline RMR (Last-RMR). Results: Mean overall CIT estimation ranged from 11.6 ± 10.0 to 20.1 ± 17.2 %RMR depending on the methods for data selection and analysis used. Regarding methods for data selection, 5min-SS-2P did not allow to observe physiologically relevant phenomena (e.g. metabolic shift in fuel oxidation; P = 0.547) due to a lack of resolution. The 5min-TI and 5min-SS-4P methods for data selection seemed to be accurate enough to observe physiologically relevant phenomena (all P < 0.014), but not comparable for estimating over-all CIT and cold-induced nutrient oxidation rates (P < 0.01). Regarding methods for data analysis, the AUC seemed to be less affected for data artefacts and to be more representative in participants with a non-stable energy expenditure during cold exposure. Conclusions: The methods for data selection and analysis can have a profound impact on CIT and cold-induced nutrient oxidation rates estimations, and therefore, it is mandatory to unify it across scientific community to allow inter-study comparisons. Based on our findings, 5min-TI should be considered the method of choice to study dynamics (i.e. changes across time) of CIT and cold-induced nutrient oxidation rates, while 5min-SS-4P and AUC should be the method of choice when computing CIT and cold-induced nutrient oxidation rates as a single value.

Mineralocorticoid Antagonism Enhances Brown Adipose Tissue Function In Humans: A Randomized Placebo-controlled Cross-over Study

Article

Mar 2019

Aim To investigate whether mineralocorticoid (MC) antagonism enhances brown adipose tissue (BAT) function in humans. Materials & Methods In a randomized double‐blind cross‐over design, 10 healthy adults (2 men, 8 women) underwent two weeks of spironolactone (100mg/day) and placebo treatments with an intervening 2‐week wash‐out. BAT function was assessed in response to cooling and to a mixed meal. Metabolic activity was measured by fluoro‐deoxyglucose (FDG) uptake (maximal standardized uptake value, SUVmax) using PET‐CT, thermogenic activity by measuring skin temperatures overlying supraclavicular (SCL) BAT depots using infrared thermography, and postprandial metabolism by measuring energy production rate (EPR) and lipid synthesis using indirect calorimetry. Results During cooling, BAT metabolic activity (SUV 6.30±2.16 vs 3.98±1.34; P<0.05) and volume (54.9±22.8 vs 21.6±11.8 cm³; P<0.05) were significantly higher, and mean SCL temperature fell by a smaller degree (‐0.3±0.2 vs ‐0.9±0.2⁰C; P=0.05) with spironolactone treatment. A mixed meal increased SCL temperature and EPR. The postprandial rise in SCL temperature (+0.4±0.1 vs +0.1±0.1⁰C; P<0.05) but not EPR was greater during spironolactone treatment. Postprandial lipid synthesis occurred in three subjects during placebo but none during spironolactone treatment (P=0.06). Conclusion MC antagonism enhanced human BAT function in response to cooling and to a meal during which lipid synthesis was suppressed. As postprandial EPR comprises energy dissipated as heat and energy required to store nutrients, the reduction in lipid synthesis during MC antagonism is a likely consequence of concurrent stimulation of BAT thermogenesis. The shift of energy usage from storage to heat dissipation indicates that MC antagonists may have therapeutic benefit for obesity. This article is protected by copyright. All rights reserved.

Postprandial Oxidative Metabolism of Human Brown Fat Indicates Thermogenesis

Article

Jun 2018
CELL METAB

Human studies suggest that a meal elevates glucose uptake in brown adipose tissue (BAT). However, in postprandial state the thermogenic activity and the metabolism of non-esterified fatty acids (NEFAs) in BAT remain unclear. Using indirect calorimetry combined with positron emission tomography and computed tomography (PET/CT), we showed that whole-body and BAT thermogenesis (oxygen consumption) increases after the ingestion of a mixed carbohydrate-rich meal, to the same extent as in cold stress. Postprandial NEFA uptake into BAT is minimal, possibly due to elevated plasma insulin inhibiting lipolysis. However, the variation in postprandial NEFA uptake is linked to BAT thermogenesis. We identified several genes participating in lipid metabolism to be expressed at higher levels in BAT compared with white fat in postprandial state, and to be positively correlated with BAT UCP1 expression. These findings suggest that substrates preferred by BAT in postprandial state are glucose or LPL-released NEFAs due to insulin stimulation.

Centennial perspective on human adaptability

Article

Mar 2018

William R. Leonard

Exercise Physiology: Nutrition, Energy, and Human Performance

Book

Jan 2010

Since publication of its First Edition in 1981, Exercise Physiology has helped more than 350,000 students build a solid foundation of the scientific principles underlying modern exercise physiology. This Seventh Edition has been thoroughly updated with all the most recent findings, guiding you to the latest understanding of nutrition, energy transfer, and exercise training and their relationship to human performance. This Seventh Edition maintains its popular seven-section structure. It begins with an exploration of the origins of exercise physiology and concludes with an examination of the most recent efforts to apply principles of molecular biology. The book provides excellent coverage of exercise physiology, uniting the topics of energy expenditure and capacity, molecular biology, physical conditioning, sports nutrition, body composition, weight control, and more. Every chapter has been fully revised and updated to reflect the latest information in the field. The updated full-color art program adds visual appeal and improves understanding of key topics. A companion website includes over 30 animations of key exercise physiology concepts; the full text online; a quiz bank; references; appendices; information about microscope technologies; a timeline of notable events in genetics; a list of Nobel Prizes in research related to cell and molecular biology; the scientific contributions of thirteen outstanding female scientists; an image bank; a Brownstone test generator; PowerPoint® lecture outlines; and image-only PowerPoint® slides.

Thermographic imaging in sports and exercise medicine: A Delphi study and consensus statement on the measurement of human skin temperature

Article

Jul 2017
J THERM BIOL

The importance of using infrared thermography (IRT) to assess skin temperature (tsk) is increasing in clinical settings. Recently, its use has been increasing in sports and exercise medicine; however, no consensus guideline exists to address the methods for collecting data in such situations. The aim of this study was to develop a checklist for the collection of tsk using IRT in sports and exercise medicine. We carried out a Delphi study to set a checklist based on consensus agreement from leading experts in the field. Panelists (n = 24) representing the areas of sport science (n=8; 33%), physiology (n=7; 29%), physiotherapy (n=3; 13%) and medicine (n=6; 25%), from 13 different countries completed the Delphi process. An initial list of 16 points was proposed which was rated and commented on by panelists in three rounds of anonymous surveys following a standard Delphi procedure. The panel reached consensus on 15 items which encompassed the participants’ demographic information, camera/room or environment setup and recording/analysis of tsk using IRT. The results of the Delphi produced the checklist entitled “Thermographic Imaging in Sports and Exercise Medicine (TISEM)” which is a proposal to standardize the collection and analysis of tsk data using IRT. It is intended that the TISEM can also be applied to evaluate bias in thermographic studies and to guide practitioners in the use of this technique.

The effect of body fat percentage and body fat distribution on skin surface temperature with infrared thermography

Article

Mar 2017
J THERM BIOL

This study aimed to search for relations between body fat percentage and skin temperature and to describe possible effects on skin temperature as a result of fat percentage in each anatomical site. Women (26.11±4.41 years old) (n =123) were tested for: body circumferences; skin temperatures (thermal camera); fat percentage and lean mass from trunk, upper and lower limbs; and body fat percentage (Dual-Energy X-Ray Absorptiometry). Values of minimum (TMi), maximum (TMa), and mean temperatures (TMe) were acquired in 30 regions of interest. Pearson's correlation was estimated for body circumferences and skin temperature variables with body fat percentage. Participants were divided into groups of high and low fat percentage of each body segment, of which TMe values were compared with Student's t-test. Linear regression models for predicting body fat percentage were tested. Body fat percentage was positively correlated with body circumferences and palm temperatures, while it was negatively correlated with most temperatures, such as TMa and TMe of posterior thighs (r =−0.495 and −0.432), TMe of posterior lower limbs (r =−0.488), TMa of anterior thighs (r =−0.406) and TMi and TMe of posterior arms (r =−0.447 and −0.430). Higher fat percentages in the specific anatomical sites tended to decrease TMe, especially in posterior thighs, shanks and arms. Skin temperatures and body circumferences predicted body fat percentage with 58.3% accuracy (R =0.764 and R2 =0.583). This study clarifies that skin temperature distribution is influenced by the fat percentage of each body segment. Abbreviations BC, Body circumference; DXA, Dual-Energy X-Ray Absorptiometry; IRT, Infrared Thermography; TMe, Skin surface mean temperature; TMi, Skin surface minimum temperature; TMa, Skin surface maximum temperature; ROI, Region of interest

Tea catechin and caffeine activate brown adipose tissue and increase cold-induced thermogenic capacity in humans

Article

Mar 2017
AM J CLIN NUTR

Background: The thermogenic effects of green tea catechin have been repeatedly reported, but their mechanisms are poorly understood. Objective: The aim of this study was to investigate the acute and chronic effects of catechin on brown adipose tissue (BAT), a site specialized for nonshivering thermogenesis, in humans. Design: Fifteen healthy male volunteers underwent fluorodeoxyglucose-positron emission tomography to assess BAT activity. To examine the acute catechin effect, whole-body energy expenditure (EE) after a single oral ingestion of a beverage containing 615 mg catechin and 77 mg caffeine (catechin beverage) was measured. Next, to investigate the chronic catechin effects, 10 men with low BAT activity were enrolled. Before and after ingestion of the catechin beverage 2 times/d for 5 wk, cold-induced thermogenesis (CIT) after 2 h of cold exposure at 19°C, which is proportional to BAT activity, was examined. Both the acute and chronic trials were single-blinded, randomized, placebo-controlled, season-matched crossover studies. Results: A single ingestion of the catechin beverage increased EE in 9 subjects who had metabolically active BAT (mean ± SEM: +15.24 ± 1.48 kcal, P < 0.01) but not in 6 subjects who had negligible activities (mean ± SEM: +3.42 ± 2.68 kcal). The ingestion of a placebo beverage containing 82 mg caffeine produced a smaller and comparative EE response in the 2 subject groups. Multivariate regression analysis revealed a significant interaction between BAT and catechin on EE (β = 0.496, P = 0.003). Daily ingestion of the catechin beverage elevated mean ± SEM CIT (from 92.0 ± 26.5 to 197.9 ± 27.7 kcal/d; P = 0.009), whereas the placebo beverage did not change it. Conclusion: Orally ingested tea catechin with caffeine acutely increases EE associated with increased BAT activity and chronically elevates nonshivering CIT, probably because of the recruitment of BAT, in humans. These trials were registered at www.umin.ac.jp/ctr/ as UMIN000016361.

Relation between brown adipose tissue and measures of obesity and metabolic dysfunction in patients with cardiovascular disease: Brown Fat, Obesity, and Metabolic Dysfunction

Article

Jan 2017

Purpose: To evaluate whether brown adipose tissue (BAT) is present in middle-aged patients with cardiovascular comorbidities and to quantify how BAT presence associates with obesity and metabolic dysfunction. Materials and methods: Supraclavicular and subcutaneous adipose tissue fat-signal-fraction (FF) was determined with 1.5T water-fat magnetic resonance imaging (MRI) in 50 patients with coronary artery disease, cerebrovascular disease, or peripheral artery disease. The association between BAT presence, as measured by a higher FF difference between supraclavicular and subcutaneous adipose tissue, and obesity and metabolic dysfunction was quantified using multivariable linear regression. Results: Supraclavicular adipose tissue displays a lower FF of 82.6% (interquartile range [IQR] 78.8-84.3) compared to 90.2% (IQR 87.3-91.9) in subcutaneous white adipose tissue (WAT, P < 0.0001). BAT presence was associated with less obesity and metabolic dysfunction. For example, 1 SD lower waist circumference (11.7 cm), 1 SD lower triglycerides (1.0 mmol/L), and absence of metabolic syndrome and type 2 diabetes were associated with 1.1% (95% confidence interval [CI] 0.1; 2.0), 1.1% (95% CI 0.1; 2.0), 2.1% (95% CI 0.1; 4.1), and 4.1% (95% CI 0.1; 7.1) higher FF difference between supraclavicular adipose tissue and subcutaneous WAT, respectively. Conclusion: Supraclavicular adipose tissue has BAT characteristics in adult patients with clinical manifest cardiovascular disease and BAT presence is associated with less obesity and a more favorable metabolic profile. Level of evidence: 2 Technical Efficacy: Stage 2 J. MAGN. RESON. IMAGING 2017;46:497-504.

Brown adipose tissue does not seem to mediate metabolic adaptation to overfeeding in men: Brown Fat and Metabolic Adaptation

Article

Jan 2017
OBESITY

Objective: Brown adipose tissue (BAT) generates heat in response to cold, and low BAT activity has been linked to obesity. However, recent studies were inconclusive as to whether BAT is involved in diet-induced thermogenesis and mitigates weight gain from prolonged overeating. Therefore, this study investigated whether BAT activity is related to metabolic adaptation arising from 8 weeks of overfeeding in humans. Methods: Fourteen men (aged 24 ± 3 years, BMI 24.5 ± 1.6 kg/m(2) ) were overfed by 40% for 8 weeks. Before and after, energy expenditure and metabolic adaptation were measured by whole-room respiratory calorimetry. A marker of BAT activity was measured using infrared imaging of the supraclavicular BAT depot. Results: At the end of 8 weeks of overfeeding, metabolic adaptation-defined as the percent increase in sleeping energy expenditure beyond that expected from weight gain-rose from -0.9 ± 3.9% to 4.7 ± 5.6% (P = 0.001). However, BAT thermal activity was unchanged (P = 0.81). Moreover, BAT thermal activity did not correlate with the degree of metabolic adaptation (P = 0.32) or with the change in body weight (P = 0.51). Conclusions: BAT thermal activity does not change in response to overfeeding, nor does it correlate with adaptive thermogenesis. Our data suggest that BAT does not mediate metabolic adaptation to overeating in humans.

Immune Modulation of Brown(ing) Adipose Tissue in Obesity

Article

Nov 2016
ENDOCR REV

Obesity is associated with a variety of medical conditions such as type 2 diabetes and cardiovascular diseases and is therefore responsible for high morbidity and mortality rates. Increasing energy expenditure by brown adipose tissue (BAT) is a current novel strategy to reduce the excessive energy stores in obesity. Brown adipocytes burn energy to generate heat and are mainly activated upon cold exposure. As prolonged cold exposure is not a realistic therapy, researchers worldwide are searching for novel ways to activate BAT and/or induce beiging of WAT. Recently the contribution of immune cells in the regulation of brown adipocyte activity and beiging of WAT has gained increased attention, with a prominent role for eosinophils and alternatively activated macrophages. This review will discuss the re-discovery of BAT, present an overview of modes of activation and differentiation of beige and brown adipocytes and describe the recently discovered immunological pathways that are key in mediating brown/beige adipocyte development and function. Interventions in immunological pathways harbour the potential to provide novel strategies to increase beige and brown adipose tissue activity as therapeutic target for obesity.

Sympathetic Innervation of Cold-Activated Brown and White Fat in Lean Young Adults

Article

May 2017

Objective: Recent work in rodents has demonstrated that basal activity of local sympathetic nervous system is critical for maintaining brown adipocyte phenotypes in classic brown (BAT) and white adipose tissue (WAT). Accordingly, we sought to assess the relationship between sympathetic innervation and cold-induced activation of BAT and WAT, and its relation to local and whole body daily energy expenditure (DEE, kcal/d) in lean young adults. Methods: Twenty adult lean normal subjects (10F/10M, 23.3 + 3.8 years, BMI = 23.7 + 2.5) underwent (11)C-meta-hydroxyephedrin (HED) and (15)O-water PET imaging at rest and following exposure to mild cold (16oC) temperature. In addition, (18)F-fluorodeoxyglucose (FDG) images were obtained during the cold stress condition to assess cold-activated BAT mass. Subjects were divided into two groups (High-BAT, Low-BAT) based on the presence of FDG tracer uptake (SUV > 2) in supraclavicular BAT (-150 < HU < -50). Blood flow and HED retention index (RI, an indirect measure of sympathetic innervation) were calculated from dynamic PET scans at the location of BAT, WAT, muscle and visceral WAT. Whole body DEE during rest and cold stress was measured by indirect calorimetry. Tissue level oxygen consumption (MRO2) in BAT was determined and used to calculate the contribution of cold-activated BAT and WAT to daily DEE. Results: FDG uptake identified subjects with high and low levels of cold-activated BAT mass (High-BAT, 96 + 37g; Low-BAT 16 + 4g). HED RI under thermoneutral conditions significantly predicted FDG uptake during cold stress (R2 = 0.68, p<0.01). The HED RI during cold stress was also highly correlated with FDG uptake (R2 = 0.73, p<0.01). In contrast to the significant increase of HED RI during cold in BAT (3.43+0.93 vs. 2.42+0.85, P = 0.02), cold exposure decreased the HED RI in WAT (0.44+0.22 vs. 0.41+0.18) as a consequence of decreased perfusion (1.22+0.20 vs. 1.12+0.16 ml/100g/min). Overall, blood flow, HED RI and SUV in BAT and WAT were highly correlated (R2~0.8), demonstrating a tight coupling between perfusion, sympathetic innervation and glucose uptake. The contribution of WAT to whole body DEE was ~150 kcal/day at rest (149+52 kcal/day) which decreased to ~100 kcal/day during cold (102+47 kcal/day). Conclusion: The level of sympathetic innervation, as determined by HED RI, can predict levels of functional BAT, as determined by FDG uptake. Overall, blood flow is the best independent predictor of HED RI and FDG uptake across thermoneutral and cold conditions. In contrast to BAT, cold stress reduces blood flow and FDG uptake in subcutaneous WAT, indicating that the physiological response is to reduce heat loss rather than to generate heat.

Sex differences in age-related changes on peripheral warm and cold innocuous thermal sensitivity

Article

May 2016
PHYSIOL BEHAV

Cutaneous thermal sensitivity to a warm and cold stimulus was compared amongst 12 older (OF, 65.2 ± 1.0 year) and 29 younger (YF, 21.6 ± 0.2 years) female participants, and 17 older (OM, 66.2 ± 1.5 years) and 13 younger (YM, 21.2 ± 0.4 years) male participants to examine the effects of ageing and sex. In a neutral condition (27.5 °C, 50% RH) during rest, warm and cold thermal sensitivity was measured on eight body regions (forehead, chest, back, forearm, hand, thigh, calf, and foot). Using the method of limits, a thermal stimulator was applied to the skin at an adapting temperature and either increased or decreased at a constant rate (0.3 °C/s) until the participants detected the temperature with a push button. Thermal sensitivity declined with ageing to both a cold (older: 1468.6 ± 744.7 W/m2, younger: 869.8 ± 654.7 W/m2, p < 0.001) and warm (older: 2127.0 ± 1208.3 W/m2, younger: 1301.7 ± 1055.2 W/m2, p < 0.001) innocuous stimulus. YF and OF were more sensitive than YM and OM to both a warm and cold stimulus (p < 0.05). There was no interaction between age and sex suggesting that whilst thermal sensitivity decreases with age the decrease is similar between the sexes (p > 0.05). There was an interaction between temperatures, age and location and it seemed that cold thermal sensitivity was more homogenous for young and older participants however warm thermal sensitivity was more heterogeneous especially in the younger participants (p < 0.05). Although the pattern was not similar between ages or sexes it was evident that the forehead was the most sensitive region to a warm and cold stimulus. Interestingly the decline in sensitivity observed with ageing occurred for all locations but was attenuated at the forehead in both males and females (p > 0.05).

Seasonal influence on stimulated BAT activity in prospective trials - A retrospective analysis of BAT visualized on 18F-FDG PET-CTs and 123I-mIBG SPECT

Article

Apr 2016
J APPL PHYSIOL

Retrospective studies have shown that outdoor temperature influences the prevalence of detectable brown adipose tissue (BAT). Prospective studies use acute cold exposure to activate BAT. In prospective studies, BAT might be preconditioned in winter months leading to an increased BAT response to various stimuli. Therefore, the aim of this study was to assess whether outdoor temperatures and other weather characteristics, modulate the response of BAT to acute cold. Methods To assess respectively metabolic BAT activity and sympathetic outflow to BAT, 64(18F)-fluorodeoxyglucose positron emission tomography CTsand 56 additional(123)I-meta-iodobenzylguanidine single photon emission computed tomography CTs of subjects participating in previously executed trials were retrospectively included. BAT activity was measured in subjects after an overnight fast, following two hours of cold exposure (~17 °C). The average daytime outdoor temperatures and other weather characteristics were obtained from the Dutch Royal Weather Institute. Results Forty-nine subjects were BAT positive. One week prior to the scan, outdoor temperature was significantly lower in the BAT positive group compared to the BAT negative group. Higher outdoor temperatures on preceding days, resulted in lower stimulated metabolic BAT activity and volume(all p<0.01). Outdoor temperatures did not correlate with sympathetic outflow to BAT. Conclusion Outdoor temperatures influences metabolic BAT activity and volume, but not sympathetic outflow to BAT, in subjects exposed to acute cold. To improve the consistency of the findings of future BAT studies in humans and to excluded bias introduced by outdoor temperatures these studies should be planned in periods of similar outdoor temperatures.

Brown adipose tissue is involved in the seasonal variation of cold-induced thermogenesis in humans

Article

Mar 2016

Infrared thermography: A non-invasive window into thermal physiology

Article

Mar 2016

Glenn J Tattersall

Infrared thermography is a non-invasive technique that measures mid to long-wave infrared radiation emanating from all objects and converts this to temperature. As an imaging technique, the value of modern infrared thermography is its ability to produce a digitized image or high speed video rendering a thermal map of the scene in false colour. Since temperature is an important environmental parameter influencing animal physiology and metabolic heat production an energetically expensive process, measuring temperature and energy exchange in animals is critical to understanding physiology, especially under field conditions. As a non-contact approach, infrared thermography provides a non-invasive complement to physiological data gathering. One caveat, however, is that only surface temperatures are measured, which guides much research to those thermal events occurring at the skin and insulating regions of the body. As an imaging technique, infrared thermal imaging is also subject to certain uncertainties that require physical modelling, which is typically done via built-in software approaches. Infrared thermal imaging has enabled different insights into the comparative physiology of phenomena ranging from thermogenesis, peripheral blood flow adjustments, evaporative cooling, and to respiratory physiology. In this review, I provide background and guidelines for the use of thermal imaging, primarily aimed at field physiologists and biologists interested in thermal biology. I also discuss some of the better known approaches and discoveries revealed from using thermal imaging with the objective of encouraging more quantitative assessment.

Practical applications of infrared thermal sensing and imaging equipment

Article

Jan 2007

H. Kaplan

The second edition of this text was published in 1999, and since that time many improvements have taken place in instrumentation performance and versatility. This third edition reviews these many changes and how they impact the way thermographers operate, deploy, calibrate, and test the new instruments. In addition, the instruments that have been made essentially obsolete are reviewed as part of the historical evolution of the technology. The purposes of this text are to: - Familiarize potential users of commercial IR sensing and imaging instruments with IR measurement and analysis basics - Provide the practical information needed for users to select the instrument most appropriate for their application - Describe how to perform valid and successful measurements in a variety of applications - Serve as a reference to help thermographers examine the validity of new applications.

Short-term Cold Acclimation Recruits Brown Adipose Tissue in Obese Humans

Article

Dec 2015

Recruitment of brown adipose tissue (BAT) has emerged as a potential tool to combat obesity and associated metabolic complications. Short-term cold acclimation has been shown not only to enhance the presence and activity of BAT in lean humans but also to improve the metabolic profile of skeletal muscle to benefit glucose uptake in patients with type 2 diabetes. Here we examined whether short-term cold acclimation also induced such adaptations in 10 metabolically healthy obese male subjects. A 10-day cold acclimation period resulted in increased coldinduced glucose uptake in BAT, as assessed by [18F]fluorodeoxyglucose positron emission tomography/computed tomography. BAT activity was negatively related to age, with a similar trend for body fat percentage. In addition, cold-induced glucose uptake in BAT was positively related to glucose uptake in visceral white adipose tissue, although glucose uptake in visceral and subcutaneous white adipose tissue depots was unchanged upon cold acclimation. Cold-induced skeletal muscle glucose uptake tended to increase upon cold acclimation, which was paralleled by increased basal GLUT4 localization in the sarcolemma, as assessed through muscle biopsies. Proximal skin temperature was increased and subjective responses to cold were slightly improved at the end of the acclimation period. These metabolic adaptations to prolonged exposure to mild cold may lead to improved glucose metabolism or prevent the development of obesity-associated insulin resistance and hyperglycemia.

Differences in Sympathetic Nervous Stimulation of Brown Adipose Tissue Between the Young and Old, and the Lean and Obese

Article

Nov 2015

Methods: This was a prospective observational study. We included 10 young obese, 11 old lean and 14 young lean healthy males. All subjects underwent a (18)F-Fluorodeoxyglucose ((18)F-FDG) PET-CT and a (123)I-meta-iodobenzylguanidine ((123)I-mIBG) SPECT-CT after an overnight fast and two hours of cold exposure. Metabolic BAT activity was expressed as volume and as maximal standardised uptake value (SUVmax) of (18)F-FDG. BAT SNS activity was expressed as volume and as the ratio between (123)I-mIBG uptake in BAT and a reference region (SQUVmax of (123)I-mIBG). Results: SUVmax, BAT volume and SQUVmax were significantly different between young and old (SUVmax 7.9[4.2-17.3] vs. 2.9[0.0-4.0], volume 124.8[10.9-338.8] vs 3.4 [0.0-10.9] and SQUVmax 2.7[1.9-4.7] vs 0.0[0.0-2.2] all p<0.01) but not between lean and obese (SUVmax 7.9[4.2-17.3] vs 4.0[0.0-13.5] P = 0.69; volume 124.8[10.9-338.8] vs 11.8 [0.0-190.2] P = 0.64 and SQUVmax 2.7[1.9-4.7]vs 1.7[0-3.5] P = 0.69). We found a strong positive correlation between BAT activity measured with (18)F-FDG and (123)I-mIBG in the whole group of BAT positive subjects (ρ=0.82, p<0.01). Conclusion: We conclude that both sympathetic drive and BAT activity are lower in older but not in obese males.

Evidence Analysis Library Review of Best Practices for Performing Indirect Calorimetry in Healthy and Non–Critically Ill Individuals

Article

May 2015

When measurement of resting metabolic rate (RMR) by indirect calorimetry is necessary, following evidence-based protocols will ensure the individual has achieved a resting state. The purpose of this project was to update the best practices for measuring RMR by indirect calorimetry in healthy and non-critically ill adults and children found the Evidence Analysis Library of the Academy of Nutrition and Dietetics. The Evidence Analysis process described by the Academy of Nutrition and Dietetics was followed. The Ovid database was searched for papers published between 2003 and 2012 using key words identified by the work group and research consultants, studies used in the previous project were also considered (1980 to 2003), and references were hand searched. The work group worked in pairs to assign papers to specific questions; however, the work group developed evidence summaries, conclusion statements, and recommendations as a group. Only 43 papers were included to answer 21 questions about the best practices to ensure an individual is at rest when measuring RMR in the non-critically ill population. In summary, subjects should be fasted for at least 7 hours and rest for 30 minutes in a thermoneutral, quiet, and dimly lit room in the supine position before the test, without doing any activities, including fidgeting, reading, or listening to music. RMR can be measured at any time of the day as long as resting conditions are met. The duration of the effects of nicotine and caffeine and other stimulants is unknown, but lasts longer than 140 minutes and 240 minutes, respectively. The duration of the effects of various types of exercise on RMR is unknown. Recommendations for achieving steady state, preferred gas-collection devices, and use of respiratory quotient to detect measurement errors are also given. Of the 21 conclusions statements developed in this systemic review, only 5 received a grade I or II. One limitation is the low number of studies available to address the questions and most of the included studies had small sample sizes and were conducted in healthy adults. More research on how to conduct an indirect calorimetry measurement in healthy adults and children and in sick, but not critically ill, individuals is needed. Copyright © 2015 Academy of Nutrition and Dietetics. Published by Elsevier Inc. All rights reserved.

The Ontogeny of Brown Adipose Tissue

Article

May 2015
ANNU REV NUTR

There are three different types of adipose tissue (AT), brown, white and beige, that differ with stage of development, species and anatomical location. Of these, brown AT (BAT) is the least abundant but has the greatest potential impact on energy balance. BAT is capable of rapidly producing large amounts of heat through activation of the unique uncoupling protein (UCP)1 located within the inner mitochondrial membrane. White AT is an endocrine organ and site of lipid storage, whilst beige AT is primarily white but contains some cells that possess UCP1. BAT first appears in the fetus around mid-gestation and is then gradually lost through childhood, adolescence and adulthood depending We focus on the inter-relationships between adipocyte classification, anatomical location and impact of diet in early life together with the extent to which this process differs between the major species examined. Ultimately this may enable novel dietary interventions designed to reactivate BAT.

Activation of Human Brown Adipose Tissue by a β3-Adrenergic Receptor Agonist

Article

Jan 2015
CELL METAB

Increasing energy expenditure through activation of endogenous brown adipose tissue (BAT) is a potential approach to treat obesity and diabetes. The class of β3-adrenergic receptor (AR) agonists stimulates rodent BAT, but this activity has never been demonstrated in humans. Here we determined the ability of 200 mg oral mirabegron (Myrbetriq, Astellas Pharma, Inc.), a β3-AR agonist currently approved to treat overactive bladder, to stimulate BAT as compared to placebo. Mirabegron led to higher BAT metabolic activity as measured via (18)F-fluorodeoxyglucose ((18)F-FDG) using positron emission tomography (PET) combined with computed tomography (CT) in all twelve healthy male subjects (p = 0.001), and it increased resting metabolic rate (RMR) by 203 ± 40 kcal/day (+13%; p = 0.001). BAT metabolic activity was also a significant predictor of the changes in RMR (p = 0.006). Therefore, a β3-AR agonist can stimulate human BAT thermogenesis and may be a promising treatment for metabolic disease. Copyright © 2015 Elsevier Inc. All rights reserved.

The “Skinny” on brown fat, obesity, and bone

Article

Feb 2015
AM J PHYS ANTHROPOL

Maureen J Devlin

The discovery that metabolically active brown fat is present in humans throughout ontogeny raises new questions about the interactions between thermoregulatory, metabolic, and skeletal homeostasis. Brown adipose tissue (BAT) is distinct from white adipose tissue (WAT) for its ability to burn, rather than store, energy. BAT uniquely expresses uncoupling protein-1 (abbreviated as UCP1), which diverts the energy produced by cellular respiration to generate heat. While BAT is found in small mammals, hibernators, and newborns, this depot was thought to regress in humans during early postnatal life. Recent studies revealed that human BAT remains metabolically active throughout childhood and even in adulthood, particularly in response to cold exposure. In addition to the constitutive BAT depots present at birth, BAT cells can be induced within WAT depots under specific metabolic and climatic conditions. These cells, called inducible brown fat, "brite," or beige fat, are currently the focus of intense investigation as a possible treatment for obesity. Inducible brown fat is associated with higher bone mineral density, suggesting that brown fat interacts with bone growth in previously unrecognized ways. Finally, BAT may have contributed to climatic adaptation in hominins. Here, I review current findings on the role of BAT in thermoregulation, bone growth, and metabolism, describe the potential role of BAT in moderating the obesity epidemic, and outline possible functions of BAT across hominin evolutionary history. Yrbk Phys Anthropol, 2014. © 2014 Wiley Periodicals, Inc.

18 F-fluorodeoxyglucose uptake in brown adipose tissue during insulin-induced hypoglycemia and mild cold exposure in non-diabetic adults

Article

Oct 2014
METABOLISM

Objective Hypoglycemia is associated with increased heat production and, despite of this, hypothermia. Heat production is likely to be mediated by sympathetic innervation. Brown adipose tissue is activated by cold exposure and stimulated by the sympathetic nervous system. We therefore examined the effect of hypoglycemia on uptake of the labeled glucose analogue 18 F-fluorodeoxyglucose in brown adipose tissue using positron emission tomography and computer tomography. Methods In nine healthy adults 18 F-fluorodeoxyglucose uptake as measure of brown adipose tissue activity was assessed in a cold environment (17 °C) during euglycemia (blood glucose 4.5 mmol/L) and hypoglycemia (2.5 mmol/L) using a hyperinsulinemic glucose clamp. Results Brown adipose tissue activity was observed in all participants. No difference was observed in the median (range) maximal standardized uptake values of 18 F-fluorodeoxyglucose in brown adipose tissue between euglycemia and hypoglycemia: 4.2 (1.0-7.7) versus 3.1 (2.2-12.5) g/mL (p = 0.7). Similarly there were no differences in mean standardized 18 F-fluorodeoxyglucose uptake values or total brown adipose tissue volume between euglycemia and hypoglycemia. Body temperature dropped by 0.6 °C from baseline during the hypoglycemic condition and remained unchanged during the euglycemic condition. There was no correlation between the maximal standardized uptake values of 18 F-fluorodeoxyglucose in brown adipose tissue and levels of counterregulatory hormones. Conclusions This study shows that there is a similar amount of 18 F-fluorodeoxyglucose uptake in brown adipose tissue during hypoglycemia when compared to euglycemia, which makes a role for systemic catecholamines in brown adipose tissue activation and a role for brown adipose tissue thermogenesis in hypoglycemia associated hypothermia unlikely. Future studies in humans should determine whether hypoglycemia indeed increases energy expenditure, and if so which alternative source can explain this increase.

Brown adipose tissue volume in healthy lean south Asian adults compared with white Caucasians: A prospective, case-controlled observational study

Article

Mar 2014

Individuals of south Asian origin have a very high risk of developing type 2 diabetes compared with white Caucasians. We aimed to assess volume and activity of brown adipose tissue (BAT), which is thought to have a role in energy metabolism by combusting fatty acids and glucose to produce heat and might contribute to the difference in incidence of type 2 diabetes between ethnic groups. We enrolled Dutch nationals with south Asian ancestry and matched Caucasian participants at The Rijnland Hospital (Leiderdorp, Netherlands). Eligible participants were healthy lean men aged 18-28 years, and we matched groups for BMI. We measured BAT volume and activity with cold-induced (18)F-fluorodeoxyglucose ((18)F-FDG) PET CT scans, and assessed resting energy expenditure, non-shivering thermogenesis, and serum parameters. This study is registered with the Netherlands Trial Register, number 2473. Between March 1, 2013, and June 1, 2013, we enrolled 12 participants in each group; one Caucasian participant developed hyperventilation after (18)F-FDG administration, and was excluded from all cold-induced and BAT measurements. Compared with Caucasian participants, south Asian participants did not differ in age (mean 23·6 years [SD 2·8] for south Asians vs 24·6 years [2·8] for Caucasians) or BMI (21·5 kg/m(2) [2·0] vs 22·0 kg/m(2) [1·6]), but were shorter (1·74 m [0·06] vs 1·85 m [0·04]) and lighter (65·0 kg [8·5] vs 75·1 kg [7·2]). Thermoneutral resting energy expenditure was 1297 kcal per day (SD 123) in south Asian participants compared with 1689 kcal per day (193) in white Caucasian participants (difference -32%, p=0·0008). On cold exposure, shiver temperature of south Asians was 2·0°C higher than Caucasians (p=0·0067) and non-shivering thermogenesis was increased by 20% in white Caucasians (p<0·0001) but was not increased in south Asians. Although the maximum and mean standardised uptake values of (18)F-FDG in BAT did not differ between groups, total BAT volume was lower in south Asians (188 mL [SD 81]) than it was in Caucasians (287 mL [169]; difference -34%, p=0·04). Overall, BAT volume correlated positively with basal resting energy expenditure in all assessable individuals (β=0·44, p=0·04). Lower resting energy expenditure, non-shivering thermogenesis, and BAT volumes in south Asian populations might underlie their high susceptibility to metabolic disturbances, such as obesity and type 2 diabetes. Development of strategies to increase BAT volume and activity might help prevent and treat such disorders, particularly in south Asian individuals. Dutch Heart Foundation (2009T038) and Dutch Diabetes Research Foundation (2012.11.1500).

Field and laboratory methods for quantifying brown adipose tissue thermogenesis

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