Obesity and Genes Again

On an almost daily basis one can find another study attempting to link obesity, especially morbid obesity, eg BMI > 30, with a purely genetic cause. The latest is an EU study by its agency CORDIS that states:

Around 7 in every 1000 morbidly obese people are missing a section of their DNA (deoxyribonucleic acid) that contains around 30 genes, say the results of an EU-funded project published in the journal Nature. The authors of the study, from Imperial College London in the UK and 10 other European research centres, suggest that the missing DNA may have a dramatic effect on the weight of the affected people.

Previous research studies have already shown several genetic variations, mostly single mutations in DNA, which can change the function of a gene, but the new research is the first to demonstrate that obesity can be caused by a rare genetic variation. The role of the missing genes is not yet known, but past studies suggest that they may be associated with delayed development, schizophrenia and autism. 

 It was a year ago when we wrote the monograph on Obesity and Type 2 Diabetes and its conclusions were correct then and even more so now. Namely as a result of the laws of nature, input less output equal net accumulation. Simply eat more than you burn and you get fat, genes not withstanding.

The discussion continues:

The researchers speculate that there may be other genetic deletions or mutations that increase the chance of obesity in certain people. Their aim is to use the latest research to develop tests to find the best way to treat morbidly obese people with mutated or missing DNA.

Commenting on the findings, Imperial College London's Professor Philippe Froguel said: 'Although the recent rise in obesity in the developed world is down to an unhealthy environment, with an abundance of unhealthy food and many people taking very little exercise, the difference in the way people respond to this environment is often genetic. 

How  is it genetic for people to willing eat more than they should. If it were illegal to have a BMI over 25 and one would be jailed than would that solve the problem? Why were the average BMI seventy years ago below 20! It is food, and lack of will power and not genes. The gene pool has not changed, much if at all. What has changed is that food in most western and advanced countries is cheap relative to incomes and it becomes a simple alternative to other "pleasures".

The writers end with:

The researchers now hope that that the results of the study may be used to identify genetic influences on other diseases such as type 2 diabetes.

Well as we had written before, there is a causality between the two. Obesity is a major causative agent of Type 2 Diabetes. Yes there are a few who have a Type 2 Diabetes and who are not obese, those are the ones we should be focusing our attention on, for that is a disease not a life style choice.

Eureka also presents some recent research on the same topic:

Researchers at the University of California, San Diego School of Medicine and Rady Children’s Hospital-San Diego say an evolutionary gene mutation that occurred in humans millions of years ago and our subsequent inability to produce a specific kind of sialic acid molecule appears to make people more vulnerable to developing type 2 diabetes, especially if they’re overweight...The findings are published in the Feb. 24 online edition of The FASEB Journal, a publication of the Federation of American Societies of Experimental Biology...Corresponding study author, Jane J. Kim, an assistant professor in the UCSD Department of Pediatrics, a member of the Pediatric Diabetes Research Center and Rady Children’s Hospital-San Diego, said the findings represent the first documented evidence linking the non-human sialic acid production to insulin and glucose metabolism problems associated with diabetes. 

 But we have argued in our monograph that based upon a plethora of prior research the obesity sets up an inflammatory response that appears to send out molecules binding to ligands that give rise to insulin suppression.

The authors continue:

Sialic acids are molecules found on the surfaces of all animal cells, where they act as vital contact points for interaction with other cells and with their surrounding environment. All mammals studied to date produce two types: N-acetylneuraminic acid (Neu5Ac) and N-glycolylneuraminic acid (Neu5Gc)...Humans are an exception. For reasons lost in the mists of evolution, a mutation in a gene called CMAH occurred about 2 to 3 million years ago, inactivating an enzyme in humans that catalyzes production of Neu5Gc by adding a single oxygen atom to Neu5Ac. ...They then developed a mouse model with a human-like defect in the CMAH gene...Kim’s group compared mice with a functional CMAH gene to mice with a human-like mutation in CMAH. Both groups of mice were fed a high-fat diet. Mice in both groups became obese and developed insulin resistance. However, only mice with the CMAH gene mutation experienced pancreatic beta cell failure. Pancreatic beta cells normally make and release insulin, a hormone that controls blood sugar level...Kim said the findings help refine understanding of why obese humans appear to be particularly vulnerable to type 2 diabetes, and also suggest that current animal models used to study diabetes may not accurately mirror the human condition. In clinical terms, she said further research to determine how sialic acid composition affects pancreatic beta cell function may reveal new strategies to preserve the cells, improve insulin production and prevent diabetes. 

 The key observations in the above are:

1. The mice had to get fat first.

2. Lacking the gene the fat mice got Type 2 Diabetes.

Although not confirmatory it is supporting that there is a causal relationship. Apparently without the gene the mice still had to get fat!