Genetic variations linked to body fat

A recent study has linked a so-called 'lean gene' to an increased likelihood of developing heart disease and type II diabetes.

Researchers from the Medical Research Council Epidemiology Unit in Cambridge, UK, combined data from 15 previous studies of over 75,000 people to see whether they could associate changes in DNA with a greater or lower fat mass. Their work identified the FTO gene, which already had an established link to increased body fat, as well as another gene, IRS1, which they found to be associated with an overall decrease in body fat.

However, this analysis goes further than previous work to compare differences in DNA that can influence body-mass index (BMI), by distinguishing lean mass from fat mass. They found that men with an IRS1 variant had proportionally less fat under the skin (subcutaneous fat) than visceral fat, which is the more dangerous type of fat, found around organs such as the heart and liver. This was unexpected in lean individuals, and is linked to an increased risk of type 2 diabetes and heart disease.

Lead researcher Dr Ruth Loos said: 'What we've discovered is that certain genetic variants keep you lean by reducing how much fat you store under your skin. We don't know for sure, but we can speculate that these individuals are then more predisposed to store fat elsewhere, such as in the liver and in muscle'.

Dr Loos suggested that the effects may be less significant in women as they are more likely to deposit fat subcutaneously rather than viscerally. This may offset the adverse effects of the IRS1 variant.

Professor Jeremy Pearson of the British Heart Foundation said: 'These results reinforce the idea that it is not just how fat you are, but where you lay down fat that’s particularly important for heart risk. Fat stored internally is worse for you than fat stored under the skin'.

Dr Iain Frame, director of research at the charity Diabetes UK, said the study could 'shed light on why 20 percent of people with type 2 diabetes have the condition despite being a healthy weight. It is also a clear message that people who appear slim shouldn't be complacent about their health'.

While this study points to the influence of genetic factors in the risk of developing these conditions, the effects are small, and lifestyle factors like eating healthily, regular exercise and not smoking play a vital role in reducing the risk. Dr Loos reiterated that the results do not change the general message for the majority: 'People who are lean are generally healthier than people who are overweight or obese'.

The study was published in Nature Genetics.