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The effect of mild cold exposure on UCP3 mRNA expression and UCP3 protein content in humans

Abstract

OBJECTIVE: In rodents, adaptive thermogenesis in response to cold exposure and high-fat feeding is accomplished by the activation of the brown adipose tissue specific mitochondrial uncoupling protein, UCP1. The recently discovered human uncoupling protein 3 is a possible candidate for adaptive thermogenesis in humans. In the present study we examined the effect of mild cold exposure on the mRNA and protein expression of UCP3.

SUBJECTS: Ten healthy male volunteers (age 24.4±1.6 y; height 1.83±0.02 m; weight 77.3±3.0 kg; percentage body fat 19±2)

DESIGN: Subjects stayed twice in the respiration chamber for 60 h (20.00–8.00 h); once at 22°C (72°F), and once at 16°C (61°F). After leaving the respiration chamber, muscle biopsies were taken and RT-competitive-PCR and Western blotting was used to measure UCP3 mRNA and protein expression respectively.

RESULTS: Twenty-four-hour energy expenditure was significantly increased at 16°C compared to 22°C (P<0.05). At 16°C, UCP3T (4.6±1.0 vs 7.7±1.5 amol/µg RNA, P=0.07), UCP3L (2.0±0.5 vs 3.5±0.9 amol/µg RNA, P=0.1) and UCP3S (2.6±0.6 vs 4.2±0.7 amol/µg RNA, P=0.07) mRNA expression tended to be lower compared with at 22°C, whereas UCP3 protein content was, on average, not different. However, the individual differences in UCP3 protein content (16–22°C) correlated positively with the differences in 24 h energy expenditure (r=0.86, P<0.05).

CONCLUSION: The present study suggests that UCP3 protein content is related to energy metabolism in humans and might help in the metabolic adaptation to cold exposure. However, the down-regulation of UCP3 mRNA with mild cold exposure suggests that prolonged cold exposure will lead to lower UCP3 protein content. What the function of such down-regulation of UCP3 could be is presently unknown.

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Acknowledgements

Dr Schrauwen is supported by a grant from The Netherlands Organization for Scientific Research (NWO). We thank Eli Lilly and Company for providing us with the UCP3 antibody. Dr H Vidal is kindly thanked for providing us with the UCP cDNA competitors.

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Schrauwen, P., Westerterp-Plantenga, M., Kornips, E. et al. The effect of mild cold exposure on UCP3 mRNA expression and UCP3 protein content in humans. Int J Obes 26, 450–457 (2002). https://doi.org/10.1038/sj.ijo.0801943

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