Genetics and the Causes of Obesity

Several countries have unfortunately earned themselves the nickname 'the super-size nation.' America, the UK and parts of western Europe are fat and getting fatter. Waistlines are expanding beyond the limits of the clothes they are contained in. Poor diet, lack of exercise and a couch potato lifestyle are some of the possible contributory reasons. But wait a minute, that's not the full picture.

For some people there is almost certainly a genetic component, and with the many health problems related to obesity, scientists are feverishly working in their labs trying to answer some very big questions. Is there an obesity gene? What are the genetics of obesity? The research on obesity genes is a very active area.

Maria De Luca and colleagues at the University of Alabama in Birmingham have made a valuable contribution to the field with their work on the humble fruit fly, Drosophila melanogaster. Although it's not really a creature known for tipping the scales, there are many similarities in the way human and fruit fly synthesise and regulate fat.

The researchers identified 4 candidate genes in fruit flies and one in particular, Laminin A (Lan A) that is associated with body weight and triglyceride storage (dietary fat is synthesised into triglycerides). This gene is similar to human LAMA5 which sits on chromosome 20.

They looked at 3 different variations of the gene in humans to see if they could spot a correlation between the gene variants and variants in body shapes. In other words, do natural variations in the LAMA5 gene play a key role in determining weight?

228 women took part in the study. So what did the researchers uncover? As reported in the journal BMC Genetics they discovered that two of the gene variants were associated with body shape. One with women of European American descent and the other in women of African American descent.

As De Luca observed. "We found one variant to be associated with weight and lean mass in both ethnic groups. This variant was also associated with height, total fat mass and HDL-cholesterol, but only in European American women. A different variant was associated with triglyceride levels and HDL-cholesterol level in African American women." In fact in one of the variants was associated with higher weight in African American women

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Of course it's not as simple as saying that if you inherit a particular version of the LAMA5 gene that you'll battle with the bulge all your life. Lifestyle and environment will play a role too. But a full understanding of all the biochemical pathways responsible for fat storage and body weight and shape does open a route for possible intervention at some stage.

If researchers find out why a specific variant results in one person storing more fat than others they can possibly do something about it. For example silencing the gene or altering it in some way that doesn't ultimately result in more fat being stored. There's along way to go before we reach that point, but this is such an important step on the road and adds to a vital body of knowledge that's been building up over recent years.

Genetic variation in a member of the laminin gene family affects variation in body composition in Drosophila and humans. Maria De Luca, Michelle Moses Chambers, Krista Casazza, Kerry H Lok, Gary R Hunter, Barbara A Gower and Jose R Fernandez. BMC Genetics 2008, 9:52