Tuesday, April 20, 2010

Obesity Gene Tied to Brain Volume Deficits in Healthy Elderly

About 46% of Western Europeans and 15% each of Asians, Hispanics, and Africans carry a gene variant (FTO) that is associated with increased fat mass (about 2-3 lbs on average) and waist size (less than an inch on average). Despite the modest numbers, this gene has been thought of as an obesity gene. In my opinion, this is nonsense. These numbers can easily be overcome with a healthy diet and reasonable exercise.

However, newer research on people with this gene variant have been found to have decreased brain mass in old age, despite generally good overall health. If this is true and is verified, then there might be reason to worry about having this gene.

Here is the relevant info from the abstract:
TO 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.
The full article is Open Access:
Ho, April J. et al. (2010). A commonly carried allele of the obesity-related FTO gene is associated with reduced brain volume in the healthy elderly. Proceedings of the National Academy of Sciences. www.pnas.org/cgi/doi/10.1073/pnas.0910878107.

Edited by Marcus E. Raichle, Washington University, St. Louis, MO.
These comments come from the end of the paper, in the discussion, and importantly, suggest that these findings can be mitigated with proper nutrition and exercise, since the correlation is partly associated with BMI:
BMI had an independent effect on the brain, over and above what is explainable by FTO, because its effect was seen in separate groups of people with the same genotype (Fig. S5; see Table S1 for subject demographics). Perhaps surprisingly, a strong effect of BMI was seen in carriers (with one or more FTO risk alleles), but it was not detected in noncarriers of the FTO allele (Fig. S5, unthresholded maps), even though the sample size for the noncarriers was larger (n = 78) than the homozygous at-risk group (n = 33) where BMI effects were still seen. Although the lack of a detectable effect of BMI in FTO noncarriers does not imply that it would not be present in a large sample, it cannot be ruled out that FTO status may influence the effect of BMI on the brain, which should be investigated when larger samples are available.

* * *

Recent studies have shown that physical activity and diet may provide promising outcomes for individuals who carry the obesity associated risk allele (39). A study of middle-aged individuals showed that a high-fat diet and low leisure-time physical activity might increase susceptibility for higher BMI in those carrying the FTO allele (39). In another study of 704 healthy adults, weight increase attributable to the presence of the risk allele was numerically less, although not significantly less, in subjects who were physically active (40). Another study showed that physical activity attenuated the genetic effect of carrying the obesity-associated risk allele on BMI and waist circumference (41). Even in individuals who are genetically susceptible to obesity, physical activity can play a major role in controlling obesity and waist circumference.

The present finding has important implications for obesity research and for combating the progression of neurodegeneration.
Another good reason to eat well and maintain a healthy weight throughout the lifespan.


Flux Poetica said...

I think you mean that the deleterious effects of obesity "can easily be overcome with a healthy diet and reasonable exercise."

Because you can't overcome the numbers, as you state. Meaning, you can't overcome the percentage of occurrence of given gene/s or the expression thereof.

I encourage you to become familiar with the correlation between obesity and fitness, as many studies have shown. The data from the President's Council on Physical Fitness and Sports supports the following data from the Harvard Health Policy Review: "[A] fit man carrying 50 pounds of body fat had a death rate less than one-half that of an unfit man with only 25 pounds of body fat." (2003)


william harryman said...

I was actually referring to the 2-3 pounds and the 1 inch of waist size - those numbers can be overcome or eliminated with healthy diet and exercise. I am very familiar with the numbers on obesity and fitness - I am a personal trainer and a science writer on health and fitness topics.

The numbers you quote on fit and fat vs. unfit and less fat are true but partial.

Carrying 50 lbs of body fat is terribly unhealthy for a number of reasons, not least of which is that fat cells generate a lot of estrogen, the hormone most closely linked with many forms of cancer. Besides cancer, that much body fat (a high BMI) is associated with decreases in brain mass and eventual cognitive decline, high blood pressure, higher risk for CVD, and so on.