An international team of researchers has identified a new gene that plays an important role in obesity and insulin resistance, a condition that increases the risk of developing type 2 diabetes and heart disease. They suggest their findings point to a potential gene therapy approach to tackle these conditions.

The researchers write about their work in a paper published online on 6 January in Nature Medicine.

In their background information the researchers explain that:

“Obesity develops as a result of altered energy homeostasis favoring fat storage.”

In other words, obesity is what happens when the finely tuned processes that regulate food absorption and energy production go awry, and the balance (homeostasis) moves in the wrong direction: towards excessive storage of fat.

Insulin resistance is a risk factor for type 2 diabetes and other health problems. It develops when the body uses insulin, which is needed to control the amount of sugar in the body, less effectively than normal. The result is raised levels of blood sugar and fats.

Specific genes make people more likely to develop insulin resistance and diabetes. Excess weight and lack of exercise also contribute to insulin resistance.

In this study, the team discovered that knocking out the gene TRIP-Br2 in mice stopped them becoming obese and developing insulin resistance. TRIP-Br2 regulates the storage of fat (adiposity) and energy use.

When the team examined the fat storage cells (adipocytes) in the knockout mice, they discovered higher levels of “lipolysis” and energy expenditure. Liopolysis is a cellular process that converts fats into lipids to supply the body with energy.

Other studies have already shown that TRIP-Br2 is more highly expressed in the visceral fat of humans, so together with the results from the knockout mice, the researchers conclude that TRIP-Br2 could be a gene therapy target for treating obesity and related conditions.

Co-author Cristina Mallol, a researcher at the Universitat Autònoma de Barcelona in Spain, summarizes their conclusion in a statement to the press:

“The protection of mice with no expression of the gene TRIP-Br2, and its selective elevation in the visceral fat of humans point the way to a future gene therapy to counteract obesity, insulin resistance and excess lipids in the blood”.

The study follows a number of discoveries of genes linked to obesity. Perhaps the most well-known of these is the FTO gene. And there have also been some surprising revelations of how this gene is linked to other conditions too.

For instance, in 2010, researchers in the US reported how they found a common variant of the FTO gene carried by more than one third of Americans that causes them to gain weight and puts them at risk for obesity, also leads to loss of brain tissue, thereby increasing their risk of developing neurodegenerative diseases like Alzheimer’s later in life.

More recently in 2011, researchers from King’s College London and the University of Oxford, reported in Nature Genetics, how they found a “master regulator gene” that controls the behavior of distant genes that exist inside fat cells. They suggest the gene, called KLF14, causes obesity and is also linked to diabetes and cholesterol.

Written by Catharine Paddock PhD