The “skinny” about the “fatso” gene FTO

Several studies have shown that variations in the FTO gene are associated with increased fatness and obesity in humans as well as, of course, mice and rats.  The gene is an ancient one.  “The FTO gene is well conserved and found in a single copy in vertebrate species including fish and chicken, suggesting that the ancestor of this gene was present 450 million years ago(ref).”  “Three independent studies have shown that variation in the fat mass and obesity-associated (FTO) gene associates with BMI and obesity(ref).”  In particular, the FTO rs9939609 gene polymorphism seems to be correlated with obesity, general morbidity and with type 2 diabetes(ref)(ref)(ref)(ref).  In a study “of a population of 362,200 Danish young men, examined for military service between 1943 and 1977, all obese (BMI>or=31.0 kg/m(2)) and a random 1% sample of the others were identified.  In 1992-94, at an average age of 46 years” – “In total 205 men died. Mortality was 42% lower (p = 0.001) with the TT genotype than in A-allele  (the FTO rs9939609 gene polymorphism) carriers. This phenomenon was observed in both the obese and the randomly sampled cohort when analyzed separately(ref).”  

Here are some things being discovered about FTO gene: The gene’s relationship to obesity apparently has more to do with food intake than metabolism.  “The accumulated data across seven independent studies therefore clearly implicates the FTO gene in humans as having a direct impact on food intake but no effect on energy expenditure(ref)”.   Low physical activity accentuates the effect of the FTO rs9939609 polymorphism on body fat accumulation.  “The association between FTO SNP rs9939609 and obesity risk may decline at older age(ref).” “The association of the examined FTO SNP to general fatness throughout the range of fatness was confirmed, and this association explains the relation between the SNP and body fat distribution and decreased insulin sensitivity and HDL-cholesterol(ref).” “Our results show: (1) A strong association between rs9939609 SNP of the FTO gene variant and obesity in Spanish morbidly obese adult patients (ref).” “Independent of fatness, the A-allele of the FTO SNP appears to increase mortality of a magnitude similar to smoking, but without a particular underlying disease pattern barring an increase in the risk of diseases of the nervous system(ref). A number of other interesting tidbits of information on the FTO gene can be found in the Wikipedia article on it.

Mouse weight-loss clinic

Because of the intron nature of the obesity-associated SNPs, it has been “unclear whether changes in FTO expression or splicing are the cause of obesity or if regulatory elements within intron 1 influence upstream or downstream genes(ref).”  An August 2009 mouse-model study report points to the FTO gene itself.  “We show that a dominant point mutation in the mouse FTO gene results in reduced fat mass, increased energy expenditure, and unchanged physical activity. Exposure to a high-fat diet enhances lean mass and lowers fat mass relative to control mice. Biochemical studies suggest the mutation occurs in a structurally novel domain and modifies FTO function, possibly by altering its dimerisation state. Gene expression profiling revealed increased expression of some fat and carbohydrate metabolism genes and an improved inflammatory profile in white adipose tissue of mutant mice. These data provide direct functional evidence that FTO is a causal gene underlying obesity(ref).”   

Sounds like mutating FTO could possibly turn out to be weight-loss approach for humans.  It worked for the mice with no reported effects except that they were skinnier and lighter.  Clearly human research is needed before this approach hits the weight-loss clinics, even the ones in Romania.

About Vince Giuliano

Being a follower, connoisseur, and interpreter of longevity research is my latest career. I have been at this part-time for well over a decade, and in 2007 this became my mainline activity. In earlier reincarnations of my career. I was founding dean of a graduate school and a university professor at the State University of New York, a senior consultant working in a variety of fields at Arthur D. Little, Inc., Chief Scientist and C00 of Mirror Systems, a software company, and an international Internet consultant. I got off the ground with one of the earliest PhD's from Harvard in a field later to become known as computer science. Because there was no academic field of computer science at the time, to get through I had to qualify myself in hard sciences, so my studies focused heavily on quantum physics. In various ways I contributed to the Computer Revolution starting in the 1950s and the Internet Revolution starting in the late 1980s. I am now engaged in doing the same for The Longevity Revolution. I have published something like 200 books and papers as well as over 430 substantive.entries in this blog, and have enjoyed various periods of notoriety. If you do a Google search on Vincent E. Giuliano, most if not all of the entries on the first few pages that come up will be ones relating to me. I have a general writings site at and an extensive site of my art at Please note that I have recently changed my mailbox to
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