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- W3193389306 abstract "Summary Disease-associated GWAS loci are predominantly scattered among noncoding regions of the human genome, which impedes causality estimation. One lead risk signal of obesity–rs1421085 T>C within the FTO gene–is reported to functional in vitro but lack of organismal evidence. Here, we established global and the brown-adipocyte specific locus-knock-in mice to recapitulate this homologous variant in humans, and discovered the minor allele (C-allele) as one candidate thermogenic locus. Mice carrying the C-alleles showed increased thermogenic capacity and a resistance to high-fat diet-induced adiposity. In terms of mechanism, the knock-in models showed enhanced FTO expression, while FTO knockdown or inhibition effectively eliminated the increased thermogenic ability of brown adipocytes. In humans, the C-allele was associated with lower birthweight, and its allele frequency increases following the environmental temperature decreases. Cumulatively, these findings demonstrated rs1421085 T>C as a functional variant regulating whole-body thermogenesis, and this variation was possibly related to early human migration from hot to cold environments." @default.
- W3193389306 created "2021-08-30" @default.
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- W3193389306 date "2021-08-15" @default.
- W3193389306 modified "2023-10-16" @default.
- W3193389306 title "The rs1421085 variant within <i>FTO</i> promotes but not inhibits thermogenesis and is potentially associated with human migration" @default.
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- W3193389306 doi "https://doi.org/10.1101/2021.08.13.456245" @default.
- W3193389306 hasPublicationYear "2021" @default.
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