A signaling pathway:
I am making an effort to present the evidence and other issues in an orderly way. Ultimately the effort is doomed, since the evidence must come first, being the most important material. But evidence will continue to emerge, simply because my basic point is the truth even though ultimately it will require constant revision like any other scientific theory. So in the future I shall have to come back to scientific issues from time to time as I am doing now.
An article has been published (E. Stice, S. Spoor, C. Bohon, and D. M. Small. Relation between obesity and blunted striatal response to food is moderated by TaqlA A1 allele SCIENCE 322 no 5900 449 October 17 2008) that is of interest. In the posting on this site of “Metabolic syndrome July 22, 2008,” I suggested that too much genetic diversity or “mixing genes, broadly speaking, might contribute to obesity and some other ills. What I proposed was that the mechanism that has proved so fruitful in accounting for so much data, (which mechanism includes the existence of chromosomes, the existence of recessive lethal mutations and the existence of mutations in genes or control systems fine tuned to each other) could also account at least in part for the current world epidemic of obesity. The present study does support my theory, but it does show that there is genetic variation in signaling pathways that are subtle. I suspect that what they have found is not quite subtle enough, but at least part of the principle is established.
The mechanism as described in the article is not the same, but it is still useful. It is more or less as follows.
The brain consists of the cerebrum, the cerebellum and the brain stem. Generally speaking it is the cerebrum that permits our brains to function in a way distinct from other animals. However, in the bottom of the cerebrum there is a structure called the corpus striatum, which is composed of layers of brain tissue and looks striped when it is sliced through at dissection. The lower part of the corpus striatum has a function that is related to the expectation of food and will not concern us further. The dorsal part of the corpus striatum is concerned with the satisfaction that comes with a meal. When one eats a meal, dopamine is released, which produces a pleasant sensation and encourages us to eat again some time. The mechanism is so important that simply giving dopamine or a chemical that acts like dopamine can produce weight loss. So far as I know, this is not now an approved regimen for obesity.
What has been found is that if the striatum receptors for dopamine are reduced in number, a person will continue to eat in order to gain the usual pleasant reward for taking nutrition, will overeat, and will tend to become overweight. Amazingly, they have even found the very gene or segment of DNA, the TaqlA in the title of the article, that is involved in responding to the dopamine signal. Furthermore, they know that this gene comes in more than one form. A2 is the standard normal form. If two copies are present, then the system functions normally. But if there is a copy or there are two copies of the A1 form, then there are thirty to forty percent fewer of the receptors, which are named D2. The team was able to do specialized brain scans on people and watch evidence for activity in the striatum in response to food and how that response varied with different genetic compositions.
The fact that there are two genes and that their presence had not been noticed until recently suggests that the effect is not terribly strong. Furthermore, obesity itself will reduce the effectiveness of the receptors, sort of a fatigue effect.
In order for the A1 and A2 forms to match my model, one would have to demonstrate somehow that there was a genetic variation in the amount of dopamine released for a given cue, and then to demonstrate that there was a correlation in the distribution of at least 2 of the forms that varied in their release and in the distribution of A1 and A2 in different populations. That is asking a lot. Also, the fact that it does not particularly make a difference whether there are 2 copies of A1 or just one, so far as I can tell, suggests that this is not a fine tuning event on a pathway, but A2 is just not a desirable gene to have. Also as I indicated earlier, the effect is probably not as subtle as the model needs.
But at least it’s a little step.
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