What is the function of the FTO (fat mass and obesity) gene?

Updated: Feb 10, 2016
  • Author: Ali Torkamani, PhD; Chief Editor: Keith K Vaux, MD  more...
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When FTO was first associated with obesity, its function was unknown; its mechanistic relationship with obesity still remains to be discovered. Bioinformatic analysis indicates that FTO is part of a family of enzymes involved in deoxyribonucleic acid (DNA) repair, fatty acid metabolism, and posttranslational modifications, and functional studies suggest that FTO is involved in nucleic acid demethylation. [11] However, it is unclear if and how nucleic acid demethylation is related to obesity.

Animal studies have demonstrated strong FTO expression in the hypothalamus, especially in the arcuate, paraventricular, dorsomedial, and ventromedial nuclei, all of which are key brain regions for the control of appetite. [11, 12] FTO -deficient mice display postnatal growth retardation, significant reduction in adipose tissue, and increased energy expenditure. [13] Conversely, mice who over-express FTO display increased adiposity and increased food intake, with no change in energy expenditure. [14]

In several human studies, individuals with at least 1 of the FTO obesity risk alleles reported increased food intake, especially of high-energy foods, as well as impaired satiety, [15, 16, 17, 18, 19, 20, 21] but changes in energy expenditure appear to be driven by changes in body mass. [22] Thus, while the exact biologic process linking FTO and obesity is unknown, it is clear that FTO variants mediate obesity by increasing energy input.

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