Two studies identify genetic influences underlying obesity

Researchers at Imperial College London have identified a genetic link to obesity. Comparing the DNA of over 13,000 obese individuals to the DNA of non-obese control subjects, they identified three SNPs (single nucleotide polymorphisms) in the PCSK1 gene that were associated with obesity. The SNPs - single 'letter' mutations in the DNA code of the PCSK1 gene - were more common in individuals who were obese than in the normal weight controls. The three SNPs identified in the study were also associated with childhood obesity, as well as less extreme weight gain.

The PCSK1 gene is an enzyme that converts inactive appetite-controlling hormones into their active form. PCSK1 also controls the hormones insulin and glucagon, which regulate the metabolism of sugars and carbohydrates in the body. Professor Philippe Froguel, who led the study, suggested that the SNPs may be responsible for altering the PCSK1 gene to a more active form, which could alter appetite levels in the body.

Most genes associated with obesity have been linked to rare genetic conditions that lead to extreme weight gain, and these genetic mutations are not common in the general population. 'This is the first time that we have found a strong link between common mutations and common obesity in the PCSK1 gene', said Professor Froguel. 'We all react differently to an environment that is becoming more and more similar, and the reason we react differently is in part genetic in origin'.

In another study, US researchers at Baylor College of Medicine in Houston, Texas, showed that the environment in the womb during the development of the fetus may increase its risk of obesity in adulthood, and that this effect can be curtailed through diet. In the International Journal of Obesity, Dr Robert Waterland and his team reported that mice with a genetic predisposition to overeating and obesity generate increasingly obese offspring with each successive generation. They suggested that the mother's diet during pregnancy was influencing the genes regulating metabolism and appetite in her offspring through epigenetic mechanisms.

Epigenetics refers to changes that affect gene activity in the body, without altering the DNA sequence of genes. One such mechanism is DNA methylation, which, through the addition a methyl group genetic tag to a gene, can switch gene activity 'off'.

To test whether epigenetic mechanisms were influencing the tendency for increasing obesity in successive generations, the research team fed the pregnant mice either a normal diet, or a diet rich in vitamins and folic acid, which is known to promote DNA methylation. The offspring from mothers who were fed a vitamin-enriched diet remained the same weight as the previous generations, whereas the offspring from mothers on a normal diet continued the trans-generational amplification of body weight. The researchers speculated that this could be because the folic acid and vitamins were promoting DNA methylation in the hypothalamus - a brain region associated with appetite and hunger - which was silencing appetite genes in the offspring. 'Why is everyone getting heavier and heavier? Maternal obesity could be promoting obesity in the next generation', Dr Waterland said.