Of Mice and Men

Obesity is a growing threat to overall health. It is not just the development of Type 2 Diabetes and its sequellae but the other sequellae that arise directly. Strangely many studies focus on mice and genetic aberrations that lead to obesity. In NEJM they discuss such a case.

They note:

A recent study by Dalgaard and colleagues forces us to rethink aspects of the heritable component of obesity. Dalgaard et al. characterized mice carrying a mutation in the gene encoding tripartite motif–containing 28 (Trim28). Trim28 is a zinc-finger transcription factor that enhances transcriptional repression — in other words, a mutation in one copy of Trim28 causes an unexpected heritable bimodal (on–off) obesity distribution that seems to depend on certain environmental factors to “flip the switch.” The average weight gain (approximately 7 g) in the obese (“on”) mouse with the Trim28 mutation was largely due to an increased mass of adipose tissue distributed uniformly across all adipose depots and a very slight increase in length (1 to 2%), whereas the weight in the “off” phenotype did not differ from that in wild-type animals. The approximate doubling of the adipose-tissue mass in the “on” phenotype was accompanied by a doubling in the number of adipocytes in the tissue.

Well first off, they are mice. Give a mouse food and they will eat it. Some more than others. I look at our bird feeder and there is one squirrel that is just stuffing herself all day. Perhaps she has a gene but also perhaps she is just a deliberate over eater. Perhaps a lot of things. Humans however have scales, they should have will power, they should see the damage caused. We humans do not exercise as much as squirrels. Thus the comparison has many faults.

Regarding humans they note:

Are these findings relevant to obesity in humans? The bimodal obesity phenotype was obvious in the inbred Trim28 mice, and the authors obtained suggestive data that polyphenism is also manifested in human populations. They observed that TRIM28 expression levels in human adipose tissue sorts samples into one of two subsets. Persons with low levels of TRIM28 expression have IGN1 dysregulation and are more likely to be obese than are persons with high levels of TRIM28 expression, a finding that is in line with the observations in mice. In addition, they report that the distributions of body-mass index within a homogeneous pediatric cohort (4000 children of European ancestry) as well as within a heterogeneous cohort (persons of black American, Mexican-American, and Han Chinese ancestries) fit two distinct gaussian distributions rather than a single gaussian distribution. However, we note that there could be other explanations (e.g., skewed social and environmental stratification) for a bimodal distribution. The regulation of TRIM28 expression in humans remains unknown.

 What does all of this mean? Good question. Humans with their will power can refrain from heavy caloric intake. There is a movement to portray obesity as a disease akin to say breast cancer. It is not, it can be controlled at no cost. Thus the search is in my opinion just another way to offset blame to some third party entity.