Genes to resist obesity

Research using genetically modified mice has revealed that some gene variants help prevent obesity. Two independent research teams will publish these findings in the journal Genes and Development on 15 August. The genes could be targeted with drugs to treat obesity in humans.

A team from Academia Sinica in Taiwan focused their research on a gene called C/EBP alpha. The team looked at mice in which the C/EBP alpha gene had been replaced by a similar gene C/EBP beta. Dr Ying-Hue Lee, who led the Taiwanese team, said, 'no doubt, C/EBP alpha is very important for life as indicated by many excellent studies related to its physiological function. Still, we wondered whether its cousin, C/EBP beta, might do the job well if given a chance'.

The researchers found that the mice with the C/EBP beta gene instead of C/EBP alpha lived an average of five months longer and were leaner, despite eating more and being no more active. The reason behind this, the researchers found, was that white adipose tissue (fat tissue), which normally stores fat, was instead burning fat. This function is normally carried out by brown adipose tissue and may be the result of another gene called Galphas.

To see the effect on obesity of replacing C/EBP alpha with C/EBP beta, the researchers induced this variation into two obese strains of mice. One of these strains has a slow metabolism, whilst the other overeats. Both had significantly reduced weight gain when alpha was replaced with beta.

The second discovery comes from the work of a team from the Howard Hughes Medical Institute in the US. The team deleted a gene from some mice, which then put on 40 per cent less weight than other mice when fed a high calorie diet. The gene, called JIP1, is involved with the effects of insulin on cells. The mice with the gene deletion had greater sensitivity to insulin and so were less likely to develop type II diabetes.

Dr Roger Davies of the US team said, 'drugs that target JIP1 may be useful for the treatment of obesity and insulin resistance. An exciting future possibility is the application of this strategy to the treatment of human obesity'.