UCP1 genetic polymorphism (-3826A/G) diminishes resting energy expenditure and thermoregulatory sympathetic nervous system activity in young females

Background: Recent findings regarding the existence of functional brown adipose tissue (BAT) in adult humans suggest a physiological role of BAT and uncoupling protein 1 (UCP1)-linked thermogenesis in energy balance. Objective: To investigate whether UCP1 polymorphism was associated with resting energy expenditure (REE) and thermoregulatory sympathetic nervous system (SNS) activity in humans. Methods: A total of 82 healthy females (20-22 years) were genotyped for the -3826 A/G polymorphism of the UCP1 gene using a fluorescent allele-specific DNA primer assay system. REE was measured by indirect calorimetry. The thermoregulatory SNS activity was assessed by heart rate variability power spectral analysis according to our previously reported method. Each subject was studied in the morning, after an overnight fast. Nutritional values were calculated on the basis of 2-day food records. Results: The frequencies of A/A, A/G and G/ G genotypes were 0.27, 0.45 and 0.28, respectively. No significant difference was found in anthropometric indexes among the three groups. However, in the G/ G group, the percentage of energy consumed as fat was lower (A/A: 30.7 +/- 1.1%, A/G: 31.3 +/- 1.0%, G/G: 26.0 +/- 1.2%, P<0.01), and energy intake tended to be lower (A/A: 7209 +/- 310 kJ d(-1), A/G: 7075 +/- 280 kJ d(-1), G/G: 6414 +/- 264 kJ d(-1), P = 0.16). With regard to metabolic parameters, group differences were observed in REE (A/A: 5599 +/- 170 kJ d(-1), A/G: 5054 +/- 115 kJ d(-1), G/G: 4919 +/- 182 kJ d(-1), P<0.01) and in thermoregulatory SNS activity (A/A: 313 +/- 47 ms(2), A/G: 333 +/- 42 ms(2), G/G: 185 +/- 23 ms(2), P<0.05). Conclusion: Diminished REE in G-allele carriers as well as reduced thermoregulatory SNS activity for the G/ G genotype, suggest that attenuated UCP1-linked thermogenesis has an adverse effect on the regulation of energy balance. International Journal of Obesity (2011) 35, 1050-1055; doi:10.1038/ijo.2010.261; published online 28 December 2010