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. 2017 Jul 17;7(1):5570.
doi: 10.1038/s41598-017-05766-3.

Experimental Evidence Reveals the UCP1 Genotype Changes the Oxygen Consumption Attributed to Non-Shivering Thermogenesis in Humans

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Free PMC article

Experimental Evidence Reveals the UCP1 Genotype Changes the Oxygen Consumption Attributed to Non-Shivering Thermogenesis in Humans

Takayuki Nishimura et al. Sci Rep. .
Free PMC article

Abstract

Humans have spread out all over the world adapting to many different cold environments. Recent worldwide genome analyses and animal experiments have reported dozens of genes associated with cold adaptation. The uncoupling protein 1 (UCP1) gene enhances thermogenesis reaction in a physiological process by blocking ATP (adenosine triphosphate) synthesis on a mitochondrial membrane in brown adipose tissues. To our knowledge, no previous studies have shown an association between variants of the UCP1 gene and physiological phenotypes concerning non-shivering thermogenesis (NST) under the condition of low temperature in humans. We showed that the degree of NST for healthy subjects in an artificial climate chamber is significantly different among UCP1 genotypes. Defining the haplotypes covering the UCP1 region (39.4 kb), we found that the frequency of the haplotype with the highest NST was significantly correlated with latitudes and ambient temperature. Thus, the data in this study provide the first evidence that the UCP1 genotype alters the efficiency of NST in humans, and likely supports the hypothesis that the UCP1 gene has been related to cold adaptation in human evolutionary history.

Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Figure 1
Figure 1
Physiological differences among UCP1 genotypes. (a) The physical positions and LD structure of UCP1 SNPs genotyped in this study. A pairwise r 2 value is shown in each square. Darker gradient color indicates higher r 2 values, and black indicates an r 2 of 1. The haplotype block defined by the Gabriel et al. method is represented by the enclosure of the black line. (b) Time series variations of VO2 (+/− s.e.m.) in each SNP and that genotype. The solid and dashed lines show the changes under 16 and 28 degrees Celsius, respectively. The colors of the lines represent each genotype (blue: a homozygote of an ancestral allele; magenta: a homozygote of a derived allele; green: heterozygote of ancestral/derived alleles). (c) Time series variations of VO2 (+/− s.e.m.) between haplotypes. The solid and dashed lines show the changes under 16 and 28 degrees Celsius, respectively. The colors of the lines represent each genotype (red: a homozygote of GnGTAn haplotype; blue: a homozygote and heterozygote of other haplotypes). The asterisks indicate a significant increase compared with other genotypes (*P < 0.05; **P < 0.01).
Figure 2
Figure 2
Correlation between the haplotype showing the highest efficiency thermogenesis and the latitudes (a) and mean annual temperatures (b) of global human populations deposited in the 1000 Genomes Project database. Blue line and grey band represent a regression line and its 95% confidence interval. Each color of triangle indicates the geographical region of populations. Dashed line represents a regression line, and orange triangle indicates the frequency and latitude of our subjects. The abbreviations used are the following: African (AFR): ESN (Esan in Nigeria), GWD (Gambian in Western Divisions in the Gambia), LWK (Luhya in Webuye, Kenya), MSL (Mende in Sierra Leone), YRI (Yoruba in Ibadan, Nigeria); European (EUR): FIN (Finnish in Finland), GBR (British in England and Scotland), IBS(Iberian Population in Spain), TSI (Toscani in Italia); East Asian (EAS): CDX (Chinese Dai in Xishuangbanna, China), CHB (Han Chinese in Bejing, China), JPT (Japanese in Tokyo, Japan), NJP (Japanese in this study), KHV (Kinh in Ho Chi Minh City, Vietnam); South Asian (SAS): BEB (Bengali from Bangladesh), PJL (Punjabi from Lahore, Pakistan).

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