Summary Brown fat defends against hypothermia and obesity through thermogenesis mediated by mitochondrial UCP1. Recent data suggest that there are two distinct types of brown fat: classical brown fat derived from a myf-5 cellular lineage and UCP1-positive cells that emerge in white fat from a non-myf-5 lineage. Here we report the cloning of “beige” cells from murine white fat depots. Beige cells resemble white fat cells in having extremely low basal expression of UCP1, but like classical brown fat, they respond to cyclic AMP stimulation with high UCP1 expression and respiration rates. Beige cells have a gene expression pattern distinct from either white or brown fat and are preferentially sensitive to the polypeptide hormone irisin. Finally, we show that deposits of brown fat previously observed in adult humans are composed of beige adipose cells. These data illustrate a new cell type with therapeutic potential in mouse and human.

The percentage of young men with brown adipose tissue is high, but its activity is reduced in men who are overweight or obese. Brown adipose tissue may be metabolically important in men, and the fact that it is reduced yet present in most overweight or obese subjects may make it a target for the treatment of obesity.

An update of practical aspects of the use of labeled water for the measurement of total body water (TBW) and energy expenditure (EE) is presented as applied in Maastricht, The Netherlands. We use a 10-hour equilibration period. The isotopes for the measurement of TBW and EE are routinely administered, after collecting a background urine sample, as a last consumption before the night. Our data show an underestimate of TBW measured with isotope dilution after 4 hours {in the morning), a discrepancy which increases with the size of TBW. No such relation and no significant differences were found after 10-hour (overnight) equilibration. The ratio between the dilution space for deuterium and oxygen-18 is higher than the earlier figure of 1.03, especially in adult subjects with a high body fat content. For an observation period of EE over two weeks, samples from the second and the last voiding on the first, mid, and last day of the observation period are collected. Differences in EE calculated from morning and evening samples within the first and second week allow detection of sampling errors and if so, samples are excluded from the final calculation. Differences of EE between weeks 1 and 2 allow a check for the consistency of the subjects' physical activity level and usually fall within 10% of the average EE over the total observation interval. Key words: isotope background, total body water, isotope dilution space, energy balance Introduction Water labeled with deuterium has been used for the measurement of total body water since the early thirties (7). Our own research using the doubly labeled water (DL W) technique started with studies in small animals (2,19). Schoeller (13) was the frrst to apply the DLW method in man, soon followed by others including ourselves (3,18).The DL W method was thoroughly discussed by the main users in 1988 (10). Here, an update of practical aspects of the use of DL W for the measurement of body composition and energy expenditure is presented, as applied in our laboratory in Maastricht. Methods for measuring body composition and energy expenditure are described separately. These are preceded by a presentation on label treatment and calculation and of the observed variation in background isotope levels. The validity of the isotope techniques is evaluated by comparing measurements with results from alternative techniques, and by analysis of the reproducibility within subjects and within observations.

Measurements of skin temperatures are often complicated because of the use of wired sensors. This is so in field studies, but also holds for many laboratory conditions. This article describes a wireless temperature system for human skin temperature measurements, i.e. the Thermochron iButton DS1291H. The study deals with validation of the iButton and its application on the human skin, and describes clinical and field measurements. The validation study shows that iButtons have a mean accuracy of -0.09 degrees C (-0.4 degrees C at most) with a precision of 0.05 degrees C (0.09 degrees C at most). These properties can be improved by using calibration. Due to the size of the device the response time is longer than that of conventional sensors, with a tau in water of 19 s. On the human skin under transient conditions the response time is significantly longer, revealing momentary deviations with a magnitude of 1 degrees C. The use of iButtons has been described in studies on circadian rhythms, sleep and cardiac surgery. With respect to circadian rhythm and sleep research, skin temperature assessment by iButtons is of significant value in laboratory, clinical and home situations. We demonstrate that differences in laboratory and field measurements add to our understanding of thermophysiology under natural living conditions. The advantage of iButtons in surgery research is that they are easy to sterilize and wireless so that they do not hinder the surgical procedure. In conclusion, the application of iButtons is advantageous for measuring skin temperatures in those situations in which wired instruments are unpractical and fast responses are not required.

The incidence of the metabolic syndrome has reached epidemic levels in the Western world. With respect to the energy balance, most attention has been given to reducing energy (food) intake. Increasing energy expenditure is an important alternative strategy. Facultative thermogenesis, which is the increase in energy expenditure in response to cold or diet, may be an effective way to affect the energy balance. The recent identification of functional brown adipose tissue (BAT) in adult humans promoted a renewed interest in nonshivering thermogenesis (NST). The purpose of this review is to highlight the recent insight in NST, general aspects of its regulation, the major tissues involved, and its metabolic consequences. Sustainable NST in adult humans amounts to 15% of the average daily energy expenditure. Calculations based on the limited available literature show that BAT thermogenesis can amount to 5% of the basal metabolic rate. It is likely that at least a substantial part of NST can be attributed to BAT, but it is possible that other tissues contribute to NST. Several studies on mitochondrial uncoupling indicate that skeletal muscle is another potential contributor to facultative thermogenesis in humans. The general and synergistic role of the sympathetic nervous system and the thyroid axis in relation to NST is discussed. Finally, perspectives on BAT and skeletal muscle NST are given.

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 cold-induced 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.

These results indicate that chronic endurance exercise is not associated with brown and beige adipocyte recruitment; in fact endurance training appears to be linked to lower the metabolic activity of BAT in humans.

Brown adipose tissue (BAT) is currently considered as a target to combat obesity and diabetes in humans. BAT is densely innervated by the sympathetic nervous system (SNS) and can be stimulated by β-adrenergic agonists, at least in animals. However, the exact role of the β-adrenergic part of the SNS in BAT activation in humans is not known yet. In this study, we measured BAT activity by 2-deoxy-2-[18F]fluoro-d-glucose ([18F]FDG) positron emission tomography/computed tomography imaging in 10 lean men during systemic infusion of the nonselective β-agonist isoprenaline (ISO) and compared this with cold-activated BAT activity. ISO successfully mimicked sympathetic stimulation as shown by increased cardiovascular and metabolic activity. Energy expenditure increased to similar levels as during cold exposure. Surprisingly, BAT was not activated during β-adrenergic stimulation. We next examined whether the high plasma free fatty acid (FFA) levels induced by ISO competed with glucose ([18F]FDG) uptake in BAT locations by blocking lipolysis with acipimox (ACI). ACI successfully lowered plasma FFA, but did not increase [18F]FDG-uptake in BAT. We therefore conclude that systemic nonselective β-adrenergic stimulation by ISO at concentrations that increase energy expenditure to the same extent as cold exposure does not activate BAT in humans, indicating that other tissues are responsible for the increased β-adrenergic thermogenesis.