FTO obesity variant mechanism (Homo sapiens)
From WikiPathways
Description
Mechanism underlying the association of FTO locus variants and obesity. The wild type T allele at rs1421085 in the FTO locus comprises a protein-DNA binding motif for ARID5B that represses the transcription of IRX3 and IRX5, which in turn de-represses a set of thermogenic genes, leading to mitochondrial thermogenesis and a browning adipocyte program. The C risk allele, on the other hand, disrupts the binding motif for ARID5B and activates a mesenchymal superenhancer and its targets, IRX3 and IRX5, which represses thermogenesis and leads to a shift to lipid storage, white adipocytes and, thus, increased risk of obesity.
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Ontology Terms
Saving...Bibliography
- Rosen CJ, Ingelfinger JR; ''Unraveling the Function of FTO Variants.''; N Engl J Med, 2015 PubMed Europe PMC Scholia
- Claussnitzer M, Dankel SN, Kim KH, Quon G, Meuleman W, Haugen C, Glunk V, Sousa IS, Beaudry JL, Puviindran V, Abdennur NA, Liu J, Svensson PA, Hsu YH, Drucker DJ, Mellgren G, Hui CC, Hauner H, Kellis M; ''FTO Obesity Variant Circuitry and Adipocyte Browning in Humans.''; N Engl J Med, 2015 PubMed Europe PMC Scholia
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External references
DataNodes
| View all... |
| Name | Type | Database reference | Comment |
|---|---|---|---|
| ARID5B | GeneProduct | ENSG00000150347 (Ensembl)  | |
| FTO rs1421085 C risk allele | GeneProduct | ||
| FTO rs1421085 T allele | GeneProduct | ||
| Fatty Acid Oxidation | Pathway | WP368 (WikiPathways) | |
| IRX3 | GeneProduct | ENSG00000177508 (Ensembl) | |
| IRX5 | GeneProduct | ENSG00000176842 (Ensembl) | |
| PPARGC1A | GeneProduct | ENSG00000109819 (Ensembl) | |
| PRDM16 | GeneProduct | ENSG00000142611 (Ensembl) | |
| TBX1 | GeneProduct | ENSG00000184058 (Ensembl) | |
| UCP1 | GeneProduct | ENSG00000109424 (Ensembl) |
Annotated Interactions
No annotated interactions
