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. 2021 Apr 28;22(9):4657.
doi: 10.3390/ijms22094657.

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

Alena A Nikanorova  1 , Nikolay A Barashkov  1 , Vera G Pshennikova  1 , Sergey S Nakhodkin  2 , Nyurgun N Gotovtsev  1 , Georgii P Romanov  1   2 , Aisen V Solovyev  1   2 , Sargylana S Kuzmina  2 , Nikolay N Sazonov  2 , Sardana A Fedorova  2
Affiliations

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

Alena A Nikanorova et al. Int J Mol Sci. .

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.

Keywords: Russia; Siberia; UCP1; Yakut population; adaptation; adipose tissue; cold climate; leptin; nonshivering thermogenesis.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Correlation between serum leptin concentrations and BMI in the Yakut population. (A) Females. (B) Males.
Figure 2
Figure 2
The leptin levels and BMI divided by the rs3811787 (UCP1) and the rs6265 (BDNF) genotypes. (A) Comparison of leptin levels by the rs3811787 (UCP1) and rs6265 (BDNF) genotypes for the group of females with normal BMI (n = 215). (B) Comparison of BMI by the rs3811787 (UCP1) and rs6265 (BDNF) genotypes for the group of females with normal BMI (n = 215). The data shown are mean ± SE. * p ≤ 0.05.
Figure 3
Figure 3
The search for indicators of natural selection for cold climate adaptation. (A) T-allele, rs3811787 (UCP1). (B) G-allele, rs6265 (BDNF). The allele prevalence gradients are indicated on the color scale. CZ—climatic zone; “North Asia”: N.YAK—northern Yakuts, V.YAK—Vilyuy Yakuts, C.YAK—central Yakuts; “South Asia”: CHB—Han Chinese, JPT—Japanese, CHS—southern Han Chinese, CDX—Chinese Dai, KHV—Vietnamese.
Figure 4
Figure 4
Possible mechanism of leptin-dependent neuro-fatty regulation of nonshivering thermogenesis. Note: WAT—white adipose tissue, LEPR—leptin receptor, BDNFPVH—BDNF neuron, AgRP—agouti-related peptide neuron, NPY—neuropeptide Y, POMC—proopiomelanocortin, HP—the hypothalamus, SNS—sympathetic nervous system, BW—browning, BeAT—beige adipose tissue, BAT—brown adipose tissue, NT—nonshivering thermogenesis, red up-arrows—increased levels of leptin or UCP1.
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