ArticleNature metabolism2023
The rs1421085 variant within FTO promotes brown fat thermogenesis.
Article in Nature metabolism, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 33 citations in OpenAlex.
- Shared and distinct genetic architectures of eating disorders and obesity: From monogenic causes to polygenic risk.Reviews in endocrine & metabolic disorders · 2026Review
- ALKBH5 activates creatine-driven thermogenesis by stabilizing CKB mRNA in response to cold.Nature metabolism · 2026Article
- Jomon genomics reveal cold adaptation in Upper Paleolithic hunter-gatherers of eastern Eurasia.Science advances · 2026Article
- N6-methyladenosine (m6A) methylation in adipose tissue: role, regulation, and therapeutic potential.Cellular and molecular life sciences : CMLS · 2026Review
- NBiomolecules · 2026Review
- Hepatogenomics of MAFLD in Asian Population: Genetic Polymorphisms and Pathway-Based Insights.Diabetes, metabolic syndrome and obesity : targets and therapy · 2026Review
- Transcriptional control of brown adipocyte differentiation and function by NFIA: recent perspectives on deciphering metabolic diseases.Journal of biochemistry · 2025Review
- FTO promotes weight gain via altering Kif1a splicing and axonal vesicle trafficking in AgRP neurons.The EMBO journal · 2025Article
- Alcohol use disorder and body mass index show genetic pleiotropy and shared neural associations.Nature human behaviour · 2025Article
- Low-Carbohydrate (Ketogenic) Diet in Children with Obesity: Part 1-Diet Impact on Anthropometric Indicators and Indicators of Metabolic Syndrome and Insulin Resistance.Diseases (Basel, Switzerland) · 2025Article
- Elucidating shared genetic association between female body mass index and preeclampsia.Communications biology · 2025Article
- Human embryo editing against disease is unsafe and unproven - despite rosy predictions.Nature · 2025Article
- TheLife metabolism · 2024Article
- Genetic-by-age interaction analyses on complex traits in UK Biobank and their potential to identify effects on longitudinal trait change.Genome biology · 2024Article
- Integrative 3D genomics with multi-omics analysis and functional validation of genetic regulatory mechanisms of abdominal fat deposition in chickens.Nature communications · 2024Article
- Annonaceous acetogenins mimic AA005 targets mitochondrial trifunctional enzyme alpha subunit to treat obesity in male mice.Nature communications · 2024Article
- Variant-to-function analysis of the childhood obesity chr12q13 locus implicates rs7132908 as a causal variant within the 3' UTR of FAIM2.Cell genomics · 2024Article
- Variant-to-function analysis of the childhood obesity chr12q13 locus implicates rs7132908 as a causal variant within the 3' UTR ofbioRxiv : the preprint server for biology · 2023Article
- Switching off the lights to illuminate a photosynthetic brake in cyanobacteria.Nature metabolism · 2023Article
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Authors and funding
19 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
One lead genetic risk signal of obesity-the rs1421085 T>C variant within the FTO gene-is reported to be functional in vitro but lacks evidence at an organism level. Here we recapitulate the homologous human variant in mice with global and brown adipocyte-specific variant knock-in and reveal that mice carrying the C-allele show increased brown fat thermogenic capacity and resistance to high-fat diet-induced adiposity, whereas the obesity-related phenotypic changes are blunted at thermoneutrality. Both in vivo and in vitro data reveal that the C-allele in brown adipocytes enhances the transcription of the Fto gene, which is associated with stronger chromatin looping linking the enhancer region and Fto promoter. Moreover, FTO knockdown or inhibition effectively eliminates the increased thermogenic ability of brown adipocytes carrying the C-allele. Taken together, these findings identify rs1421085 T>C as a functional variant promoting brown fat thermogenesis.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.