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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°minimum −71.2 °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.

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