ArticleJournal of physiological anthropology2024
Association between thermogenic brown fat and genes under positive natural selection in circumpolar populations.
Article in Journal of physiological anthropology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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5 citing papers in PubMed.
- The Genomic Basis of the Svalbard Reindeer's Adaptation to an Extreme Arctic Environment.Genome biology and evolution · 2025Article
- Brown fat thermogenesis and cold adaptation in humans.Journal of physiological anthropology · 2025Review
- Infrared thermography unveiled the variation of brown adipose tissue thermogenesis among East Asian adults.Physiological reports · 2025Article
- Recent updates on cold adaptation in population and laboratory studies, including cross-adaptation with nonthermal factors.Journal of physiological anthropology · 2025Review
- Human dispersal into East Eurasia: ancient genome insights and the need for research on physiological adaptations.Journal of physiological anthropology · 2025Review
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Abstract
backgroundAdaptation to cold was essential for human migration across Eurasia. Non-shivering thermogenesis through brown adipose tissue (BAT) participates in cold adaptation because some genes involved in the differentiation and function of BAT exhibit signatures of positive natural selection in populations at high latitudes. Whether these genes are associated with the inter-individual variability in BAT thermogenesis remains unclear. In this study, we evaluated the potential associations between BAT activity and single nucleotide polymorphisms (SNPs) in candidate gene regions in East Asian populations.
methodsBAT activity induced by mild cold exposure was measured in 399 healthy Japanese men and women using fluorodeoxyglucose-positron emission tomography and computed tomography (FDG-PET/CT). The capacity for cold-induced thermogenesis and fat oxidation was measured in 56 men. Association analyses with physiological traits were performed for 11 SNPs at six loci (LEPR, ANGPTL8, PLA2G2A, PLIN1, TBX15-WARS2, and FADS1) reported to be under positive natural selection. Associations found in the FDG-PET/CT population were further validated in 84 healthy East Asian men and women, in whom BAT activity was measured using infrared thermography. Associations between the SNP genotypes and BAT activity or other related traits were tested using multiple logistic and linear regression models.
resultsOf the 11 putative adaptive alleles of the six genes, two intronic SNPs in LEPR (rs1022981 and rs12405556) tended to be associated with higher BAT activity. However, these did not survive multiple test comparisons. Associations with lower body fat percentage, plasma triglyceride, insulin, and HOMA-IR levels were observed in the FDG-PET/CT population (P < 0.05). Other loci, including TBX15-WARS2, which is speculated to mediate cold adaptation in Greenland Inuits, did not show significant differences in BAT thermogenesis.
conclusionsOur results suggest a marginal but significant association between LEPR SNPs. However, robust supporting evidence was not established for the involvement of other loci under positive natural selection in cold adaptation through BAT thermogenesis in East Asian adults. Given the pleiotropic function of these genes, factors other than cold adaptation through BAT thermogenesis, such as diet adaptation, may contribute to positive natural selection at these loci.
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