Impact of Chronic Cold Exposure in Humans (ICEMAN) Study: Evidence for Brown Adipose Tissue Plasticity Modulating Glucose Metabolism in Humans

Program: Abstracts - Orals, Poster Preview Presentations, and Posters
Session: SUN 0875-0890-Adipocyte Biology-Clinical studies
Sunday, June 22, 2014: 1:00 PM-3:00 PM
Hall F (McCormick Place West Building)

Poster Board SUN-0887

Helmsley Charitable Trust Abstract Awards in Type 1 Diabetes
Paul Lee, M.D., Ph.D1, Sheila Smith, RN1, Joyce D Linderman, RN1, Amber B Courville, Ph.D2, Robert J Brychta, Ph.D1, William Dieckmann3, Charlotte D Werner, B.Sc.1, Kong Chen, Ph.D1 and Francesco S. Celi, M.D., M.H.Sc.4
1Diabetes Endocrinology Obesity Branch, NIDDK, NIH, Bethesda, MD, 2Clinical Center, NIH, Bethesda, MD, 3PET Department, NIH, Bethesda, MD, 4Virginia Commonwealth University, Richmond, VA
In addition to heat production during cold exposure, growing evidence suggests brown adipose tissue (BAT) may contribute to healthy metabolism in humans (1). Even a mild reduction in environmental temperature is sufficient to activate BAT (2) and induce hormonal changes (3). However, the long-term consequences of temperature acclimatization on BAT, and whether it impacts on whole body energy/substrate metabolism in humans, are unclear. 

In this study, we examined the impact of controlled temperature acclimatization on BAT and energy homeostasis in five men (21±2 years old, BMI: 22±1 kg/m2, body fat: 21±2%) over a 4-month period. Volunteers engaged in usual daytime activities but slept in a temperature-adjusted private room: 24°C (month 1) → 19°C (month 2) → 24°C (month 3) → 27°C (month 4). Personal temperature detectors monitored individual exposed temperature continuously for the entire 4-month period. At the end of each testing month, BAT was quantified by Positron Emission Tomography (PET)-CT scanning and energy metabolism by whole room indirect calorimetry, mixed meal test, blood hormonal/substrate profiling and adipose/muscle biopsies ex vivo analyses.

During the 4-month period, mean BAT volume and overall fat metabolic activity increased upon cold acclimatization (19°C) by 42±18% (p<0.05) and 10±11% (p<0.05), respectively; decreased after the thermoneutral month (24°C) to nearly baseline level, and completely muted at the end of one-month warm exposure (27°C). Room (p<0.05) and individually exposed temperatures (p<0.01), but not outdoor temperatures, correlated with BAT changes during study period. BAT-acclimatization was accompanied by diet-induced thermogenesis and post-prandial glucose metabolism enhancement, evident only after cold exposure. Mechanistically, BAT acclimatization was associated with reciprocal changes of circulating adiponectin and leptin levels, mirrored by corresponding transcriptosomal changes in adipose tissue ex vivo.

In summary, sequential monthly acclimatization modulated BAT reversibly, boosting and suppressing its abundance and activity in mild cold and warm conditions, respectively, independent of seasonal fluctuations. The inducibility and suppressibility of human BAT paralleling whole body metabolic changes suggests regulatory links between BAT thermal plasticity and glucose metabolism in humans. We propose BAT enhancement as a promising therapeutic strategy to improve glycemia in humans.

(1) Lee et al., Endocr Rev. 2013; 34:413. (2) Chen et al., J Clin Endocrinol Metab. 2013; 98:E1218. (3) Celi et al., Eur J Endocrinol. 2010; 163:863.

Nothing to Disclose: PL, SS, JDL, ABC, RJB, WD, CDW, KC, FSC

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Sources of Research Support: Paul Lee was supported by an Australian National Health Medical Research Council (NHMRC) Early Career Fellowship, the Diabetes Australia Fellowship and Bushell Travelling Fellowship, and the School of Medicine, University of Queensland. This study was supported by the Intramural Research Program Z01-DK047057-07 of NIDDK and the NIH Clinical Center.