Published on May 4, 2010 in Proc Natl Acad Sci USA volume 107(18).

PubMed ID: 20404173

DOI: 0910878107

Abstract:

A recently identified variant within the fat mass and obesity-associated (FTO) geneis carried by 46% of Western Europeans and is associated with an approximately 1.2kg higher weight, on average, in adults and an approximately 1 cm greater waistcircumference. With >1 billion overweight and 300 million obese persons worldwide,it is crucial to understand the implications of carrying this very common allele forthe health of our aging population. FTO is highly expressed in the brain andelevated body mass index (BMI) is associated with brain atrophy, but it is unknownhow the obesity-associated risk allele affects human brain structure. We thereforegenerated 3D maps of regional brain volume differences in 206 healthy elderlysubjects scanned with MRI and genotyped as part of the Alzheimer's DiseaseNeuroimaging Initiative. We found a pattern of systematic brain volume deficits incarriers of the obesity-associated risk allele versus noncarriers. Relative tostructure volumes in the mean template, FTO risk allele carriers versus noncarriershad an average brain volume difference of approximately 8% in the frontal lobes and12% in the occipital lobes-these regions also showed significant volume deficits insubjects with higher BMI. These brain differences were not attributable todifferences in cholesterol levels, hypertension, or the volume of white matterhyperintensities; which were not detectably higher in FTO risk allele carriersversus noncarriers. These brain maps reveal that a commonly carried susceptibilityallele for obesity is associated with structural brain atrophy, with implicationsfor the health of the elderly.