Cold-Activated Brown Adipose Tissue in Healthy Men

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Abstract

Studies in animals indicate that brown adipose tissue is important in the regulation of body weight, and it is possible that individual variation in adaptive thermogenesis can be attributed to variations in the amount or activity of brown adipose tissue. Until recently, the presence of brown adipose tissue was thought to be relevant only in small mammals and infants, with negligible physiologic relevance in adult humans. We performed a systematic examination of the presence, distribution, and activity of brown adipose tissue in lean and obese men during exposure to cold temperature. Brown-adipose-tissue activity was studied in relation to body composition and energy metabolism. We studied 24 healthy men--10 who were lean (body-mass index [BMI] [the weight in kilograms divided by the square of the height in meters], < 25) and 14 who were overweight or obese (BMI, > or = 25)--under thermoneutral conditions (22 degrees C) and during mild cold exposure (16 degrees C). Putative brown-adipose-tissue activity was determined with the use of integrated (18)F-fluorodeoxyglucose positron-emission tomography and computed tomography. Body composition and energy expenditure were measured with the use of dual-energy x-ray absorptiometry and indirect calorimetry. Brown-adipose-tissue activity was observed in 23 of the 24 subjects (96%) during cold exposure but not under thermoneutral conditions. The activity was significantly lower in the overweight or obese subjects than in the lean subjects (P=0.007). BMI and percentage of body fat both had significant negative correlations with brown adipose tissue, whereas resting metabolic rate had a significant positive correlation. 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. 2009 Massachusetts Medical Society

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Transcriptional control of brown fat determination by PRDM16.

Patrick Seale, Shingo Kajimura, Wenli Yang … (2007)

Brown fat cells are specialized to dissipate energy and can counteract obesity; however, the transcriptional basis of their determination is largely unknown. We show here that the zinc-finger protein PRDM16 is highly enriched in brown fat cells compared to white fat cells. When expressed in white fat cell progenitors, PRDM16 activates a robust brown fat phenotype including induction of PGC-1alpha, UCP1, and type 2 deiodinase (Dio2) expression and a remarkable increase in uncoupled respiration. Transgenic expression of PRDM16 at physiological levels in white fat depots stimulates the formation of brown fat cells. Depletion of PRDM16 through shRNA expression in brown fat cells causes a near total loss of the brown characteristics. PRDM16 activates brown fat cell identity at least in part by simultaneously activating PGC-1alpha and PGC-1beta through direct protein binding. These data indicate that PRDM16 can control the determination of brown fat fate.

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Seasonal changes in metabolic and temperature responses to cold air in humans.

W D van Marken Lichtenbelt, M. Dam, K Westerterp … (2004)

The metabolic and temperature response to mild cold were investigated in summer and winter in a moderate oceanic climate. Subjects were 10 women and 10 men, aged 19-36 years and BMI 17-32 kg/m2. Metabolic rate (MR) and body temperatures were measured continuously in a climate chamber with an ambient temperature of 22 degrees C for 1 h and subsequently 3 h of 15 degrees C. The average metabolic response during cold exposure, measured as the increase in kJ/min over time, was significantly higher in winter (11.5%) compared to summer (7.0%, P < .05). The temperature response was comparable in both seasons. The metabolic response in winter was significantly related to the response in summer (r2 = .47, P < .001). Total heat production during cold exposure was inversely related to the temperature response in both seasons (summer, r2 = .39, P < .01; winter r2 = .32, P < .05). In conclusion, the observed higher metabolic response in winter compared to summer indicates cold adaptation. The magnitude of the cold response varies, but the relative contribution of metabolic and temperature response was subject specific and consistent throughout the seasons, which can have implications for energy balance and body composition.