Research
Hormonal
Knocking down IRX3 or IRX5 in adipocytes from individuals with the FTO risk allele restores mitochondrial thermogenesis by a factor of 7, effectively reversing the obesity-associated phenotype.
This finding suggests that future drugs targeting IRX3 or IRX5 could help people with the FTO obesity gene burn more fat. It is not a current lifestyle intervention but a promising area for pharmaceutical development.
StrongSupportsVERY_HIGH confidence
Knockdown of IRX3 or IRX5 in primary adipocytes from participants with the risk allele restored thermogenesis, increasing it by a factor of 7, and overexpression of these genes had the opposite effect in adipocytes from nonrisk-allele carriers.
Why this rating
Validated by CRISPR editing and knockdown in human primary cells and mouse models.
Source
<i>FTO</i> Obesity Variant Circuitry and Adipocyte Browning in Humans
Melina Claussnitzer et al. · New England Journal of Medicine · 2015
DOI 10.1056/nejmoa1502214
mechanism_only · n=112Cited 1,389×
Read the paper DOI resolved against Crossref · corpus check 2026-06-10
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