Agência FAPESP – Um gene ligado à obesidade, presente em quase metade dos europeus ocidentais, pode estar também associado com a degeneração cerebral. A conclusão é de um estudo que será publicado esta semana no site e em breve na edição impressa da revista Proceedings of the National Academy of Sciences.
Para fazer a pesquisa, Paul Thompson, da Escola de Medicina da Universidade da Califórnia, em Los Angeles, e colegas produziram mapas em três dimensões dos cérebros de 206 caucasianos idosos e saudáveis.
Estudo encontra relação entre a presença de um gene específico ligado à obesidade e degeneração do cérebro. Gene é comum em metade dos europeus ocidentais (divulgação)
Segundo os autores do estudo, as diferenças com relação aos demais voluntários não são atribuídas a outros fatores ligados à obesidade, como nível de colesterol, diabetes e pressão alta.
Trabalhos anteriores observaram que o alelo, que está associado com circunferência abdominal e altura maiores do que a média, está presente em 46% dos europeus ocidentais e centrais e em 16% dos asiáticos.
Os autores destacam que a obesidade é um fator conhecido para o declínio cognitivo e que o novo estudo não identificou o mecanismo por trás da atrofia cerebral nos portadores do alelo.
Segundo eles, até o momento não foi possível determinar se a influência genética dessa sequência está entre os fatores determinantes da obesidade. Os pesquisadores apontam que essa variante genética pode contribuir com a degeneração cerebral independentemente (ou além) da influência sobre a massa corporal dos portadores.
O artigo A commonly carried allele of the obesity-related FTO gene is associated with reduced brain volume in healthy elderly (doi: 10.1073/pnas.0910878107), de Paul Thompson e outros, poderá ser lido em breve por assinantes daPnas em www.pnas.org.
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A commonly carried allele of the obesity-related FTO gene is associated with reduced brain volume in the healthy elderly
April J. Ho a,1, Jason L. Stein a,1, Xue Hua a, Suh Lee a, Derrek P. Hibar a, Alex D. Leow a,b, Ivo D. Dinov a, Arthur W. Toga a, Andrew J. Saykin c, Li Shen c, Tatiana Foroud d, Nathan Pankratz d, Matthew J. Huentelman e, David W. Craig e, Jill D. Gerber e, April N. Allen e, Jason J. Corneveaux e, Dietrich A. Stephan f, Charles S. DeCarli g, Bryan M. DeChairo h, Steven G. Potkin i, Clifford R. Jack Jr. j, Michael W. Weiner k,l, Cyrus A. Raji m, Oscar L. Lopez n, James T. Becker o,p,q, Owen T. Carmichael r, Paul M. Thompson a,2, and the Alzheimer's Disease Neuroimaging Initiative†
+Author Affiliations
aLaboratory of Neuroimaging, Department of Neurology, University of California School of Medicine, Los Angeles, CA 90095;
bResnick Neuropsychiatric Hospital at University of California, Los Angeles, CA 90095;
cCenter for Neuroimaging, Department of Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, IN 46202;
dDepartment of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN 46202;
e Translational Genomics Research Institute, Phoenix, AZ 85004;
f Ignite Institute for Individualized Health, Fairfax, VA 22042;
gCenter for Neuroscience, University of California, Davis, CA 95616;
hNeuroscience and Molecular Medicine, Pfizer Global Research and Development, New London, CT 06320;
iDepartment of Psychiatry and Human Behavior, University of California, Irvine, CA 92697;
j Mayo Clinic, Rochester, MN 55905;
kDepartments of Radiology, Medicine, and Psychiatry, University of California, San Francisco, CA 94143;
l Department of Veterans Affairs Medical Center, San Francisco, CA 94121;
Departments of mRadiology,
nEpidemiology,
oPsychiatry,
pPsychology,
qNeurology, University of Pittsburgh, Pittsburgh, PA 15213; and
rDepartment of Neurology and Computer Science, University of California, Davis, CA 95616
Edited* by Marcus E. Raichle, Washington University, St. Louis, MO, and approved March 9, 2010 (received for review September 22, 2009)
Abstract
A recently identified variant within the fat mass and obesity-associated (FTO) gene is carried by 46% of Western Europeans and is associated with an ~1.2 kg higher weight, on average, in adults and an ~1 cm greater waist circumference. With >1 billion overweight and 300 million obese persons worldwide, it is crucial to understand the implications of carrying this very common allele for the health of our aging population. FTO is highly expressed in the brain and elevated body mass index (BMI) is associated with brain atrophy, but it is unknown how the obesity-associated risk allele affects human brain structure. We therefore generated 3D maps of regional brain volume differences in 206 healthy elderly subjects scanned with MRI and genotyped as part of the Alzheimer's Disease Neuroimaging Initiative. We found a pattern of systematic brain volume deficits in carriers of the obesity-associated risk allele versus noncarriers. Relative to structure volumes in the mean template, FTO risk allele carriers versus noncarriers had an average brain volume difference of ~8% in the frontal lobes and 12% in the occipital lobes—these regions also showed significant volume deficits in subjects with higher BMI. These brain differences were not attributable to differences in cholesterol levels, hypertension, or the volume of white matter hyperintensities; which were not detectably higher in FTO risk allele carriers versus noncarriers. These brain maps reveal that a commonly carried susceptibility allele for obesity is associated with structural brain atrophy, with implications for the health of the elderly.
Alzheimer's Disease Neuroimaging Initiative
body mass index
brain structure
tensor-based morphometry
obesity
Footnotes
2To whom correspondence should be addressed. E-mail:thompson@loni.ucla.edu.
Author contributions: A.J.H., J.L.S., P.M.T., and the ADNI designed research; A.J.H., J.L.S., S.L., D.P.H., C.A.R., P.M.T., and the ADNI performed research; A.D.L., I.D.D., A.W.T., A.J.S., L.S., T.F., N.P., M.J.H., D.C., J.D.G., A.N.A., J.C., D.A.S., C.D., B.M.D., S.G.P., C.R.J., M.W.W., O.L.L., J.T.B., O.T.C., and P.M.T. contributed new reagents/analytic tools; A.J.H., J.L.S., X.H., and P.M.T. analyzed data; and A.J.H., J.L.S., and P.M.T. wrote the paper.
↵1 A.J.H. and J.L.S. contributed equally to this work.
The authors declare no conflict of interest.
↵*This Direct Submission article had a prearranged editor.
↵ †Data used in the preparation of this article were obtained from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database (www.loni.ucla.edu/ADNI). As such, the investigators within the ADNI contributed to the design and implementation of ADNI and/or provided data but did not participate in analysis or writing of this report. A complete listing of ADNI investigators is available at http://www.loni.ucla.edu/ADNI/Collaboration/ADNI_Manuscript_Citations.pdf.
This article contains supporting information online at www.pnas.org/cgi/content/full/0910878107/DCSupplemental.
Freely available online through the PNAS open access option.
