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

Abstract

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.

NGS Sequencing Reveals New UCP1 Gene Variants Potentially Associated with MetS and/or T2DM Risk in the Polish Population—A Preliminary Study

“…In a subsequent study in Korean women, Cha et al found an association between rs3811787 and rs1800592 and body fat accumulation and obesity [ 30 ]. Moreover, Nikaranova’s study [ 32 ] showed the influence of rs3811787 on the leptin-mediated thermoregulation mechanism. In this study, the prevalence gradient of the rs3811787T allele of UCP1 increased from the south to the north across Eurasia, along the shore of the Arctic Ocean.…”

“…In this study, the prevalence gradient of the rs3811787T allele of UCP1 increased from the south to the north across Eurasia, along the shore of the Arctic Ocean. Thereby, the authors suggest the potential involvement of the UCP1 gene, in particular the rs3811787 T allele, in better activation of the UCP1 gene and higher activity of BAT [ 32 ]. Our very preliminary data also confirmed the decreased risk of T2DM individuals possessing the rs3811787 TT genotype.…”

“… * Cha et al 2008 [ 30 ], Jin et al 2020 [ 31 ], Nikanorova et al 2021 [ 32 ]; ** potentially associated with susceptibility to disorder, + yes; - not associated. …”

Relationships between Uncoupling Protein Genes UCP1, UCP2 and UCP3 and Irisin Levels in Residents of the Coldest Region of Siberia

“…Polymerase chain reaction was performed on a BioRad T100 Thermal Cycler (Bio-Rad Laboratories, Inc., Hercules, CA, USA). The data, including the PCR product size, primer sequence, annealing temperature, and restriction enzymes, are given in Supplementary Table S1 [ 35 ].…”

Environmental determinants of human milk composition in relation to health outcomes

“…Interestingly, two studies compared populations from higher and lower altitude regions of Tibet, reporting that living at higher altitude had no effect on HM macronutrient content, 16 but was related to higher HM adiponectin and lower leptin concentrations; however, this could be in part explained by the higher body mass index (BMI) of mothers from lower altitude, 17 or lower circulating leptin as an adaption to colder climate in mothers from higher altitudes 18 …”