Researchers Link FTO Gene to Increased Ghrelin Levels

A new study has reportedly detailed how a common gene variant linked
to obesity affects the production and reception of ghrelin, the hormone
responsible for stimulating hunger. Efthimia Karra, et al., “A link between
FTO, ghrelin, and impaired brain food-cue responsivity,” Journal of Clinical
Investigation, July 2013. According to a July 15, 2013, press release, in
the first part of the study, researchers with University College London, the
Medical Research Council and King’s College London Institute of Psychiatry
analyzed ghrelin levels and other indicators of hunger from two groups of
participants—those with the high obesity-risk FTO gene (AA group) and those
with the low obesity-risk version (TT group)—who were perfectly matched for
body weight, fat distribution and social factors such as education level. The
results evidently showed that AA group participants not only reported feeling
hungrier after a meal than their TT group counterparts, but had “much higher
circulating ghrelin levels,” suggesting “that the obesity-risk variant (AA) group
do not suppress ghrelin in a normal way after a meal.”

The second part of the study apparently relied on functional magnetic
resonance imaging (fMRI) “to measure how the brain responds to pictures of
high-calorie and low-calorie food images, and non-food items, before and
after a meal.” In this scenario, those with the FTO gene variant “rated pictures
of high-calorie foods as more appealing after a meal than the low-risk group,”
and the fMRI “revealed that the brains of the two groups responded differently
to food images (before and after a meal) and to circulating levels of ghrelin.”
To explain these differences, researchers over-expressed the FTO gene in
mouse and human cells “and found that this altered the chemical make-up of
ghrelin mRNA (the template for the ghrelin protein) leading to higher levels of
ghrelin itself.”

“What this study shows us is that individuals with two copies of the obesity-risk
FTO variant are biologically programmed to eat more. Not only do these
people have higher ghrelin levels and therefore feel hungrier, their brains
respond differently to ghrelin and to pictures of food—it’s a double hit,”
the lead author was quoted as saying. “At a therapeutic level this arms us
with some important new insights to help in the fight against the obesity
pandemic. For example, we know that ghrelin (and therefore hunger) can be
reduced by exercise like running and cycling, or by eating a high-protein diet.
There are also some drugs in the pipeline that suppress ghrelin, which might
be particularly effective if they are targeted to patients with the obesity-risk
variant of the FTO gene.”