The Role of Nonshivering Thermogenesis Genes on Leptin Levels Regulation in Residents of the Coldest Region of Siberia

Leptin plays an important role in thermoregulation and is possibly associated with the microevolutionary processes of human adaptation to a cold climate. In this study, based on the Yakut population (n = 281 individuals) living in the coldest region of Siberia (t degrees minimum -71.2 degrees C), we analyze the serum leptin levels and data of 14 single nucleotide polymorphisms (SNPs) of 10 genes (UCP1, UCP2, UCP3, FNDC5, PPARGC1A, CIDEA, PTGS2, TRPV1, LEPR, BDNF) that are possibly involved in nonshivering thermogenesis processes. Our results demonstrate that from 14 studied SNPs of 10 genes, 2 SNPs (the TT rs3811787 genotype of the UCP1 gene and the GG rs6265 genotype of the BDNF gene) were associated with the elevated leptin levels in Yakut females (p < 0.05). Furthermore, of these two SNPs, the rs3811787 of the UCP1 gene demonstrated more indications of natural selection for cold climate adaptation. The prevalence gradient of the T-allele (rs3811787) of UCP1 increased from the south to the north across Eurasia, along the shore of the Arctic Ocean. Thereby, our study suggests the potential involvement of the UCP1 gene in the leptin-mediated thermoregulation mechanism, while the distribution of its allelic variants is probably related to human adaptation to a cold climate.

Automated summary

Analysis of data from the Yakut population suggests that specific genotypes of the UCP1 and BDNF genes are associated with elevated levels of leptin in females, with UCP1's rs3811787 showing more signs of natural selection possibly related to cold climate adaptation. The distribution of the T-allele (rs3811787) of UCP1 increases from south to north across Eurasia, along the Arctic Ocean shore, indicating a potential role of the UCP1 gene in leptin-mediated thermoregulation mechanism and its allelic variants in human adaptation to cold climate.