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 AE 1.6 y; height 1.83 AE 0.02 m; weight 77.3 AE 3.0 kg; percentage body fat 19 AE 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 AE 1.0 vs 7.7 AE 1.5 amol=mg RNA, P ¼ 0.07), UCP3L (2.0 AE 0.5 vs 3.5 AE 0.9 amol=mg RNA, P ¼ 0.1) and UCP3S (2.6 AE 0.6 vs 4.2 AE 0.7 amol=mg RNA, P ¼ 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 ¼ 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.

Individual Thermogenic Responses to Mild Cold and Overfeeding Are Closely Related

“…Another potential mechanism in humans is uncoupling by UCP-3, a UCP-1 homolog that is present in skeletal muscle tissue. However, it has been shown that the UCP-3 protein content and mRNA expression have not been increased after mild cold exposure (41). On the other hand, FFA are known to stimulate UCP-3 activity (42).…”

Minimal changes in environmental temperature result in a significant increase in energy expenditure and changes in the hormonal homeostasis in healthy adults

“…While no changes were observed in the BAT-specific transcripts in the subcutaneous adipose tissue, it is possible that longer duration of exposure to 19 °C could stimulate transcription of BAT-specific genes (35, 36). However, the actual contribution of BAT to the maintenance of energy balance in humans has not been empirically demonstrated, and it is possible that other tissues such as skeletal muscle may play a major role in adaptive thermogenesis in adult humans (37). …”

Uncoupling protein 3 and physical activity: the role of uncoupling protein 3 in energy metabolism revisited

“…However, UCP3 mRNA expression is down regulated, suggesting that prolonged cold exposure also decreases UCP3 protein content. Thus, this result indicates that, although basal UCP3 protein content is related to energy metabolism, the function of UCP3 is not in the adaptation to cold (Schrauwen et al 2002c). Recently, de Lange et al (2001) reported evidence of a role for UCP3 in thyroid hormone-induced thermogenesis.…”