A University of Ottawa Heart Institute (UOHI) research team has unlocked the mechanism that turns on a weight-loss gene in muscle. A new UOHI study shows that the mechanism – a DNA sequence variant identified as rs2419621 – increases the activity levels of ACSL5, among the first genes associated with weight loss, and enables rapid weight loss in people who are dieting.

Heart Institute scientists working with The Ottawa Hospital Weight Management Clinic had previously identified the ACSL5 gene, which influences how quickly overweight people lose weight in response to diet. Unlocking the mechanism to activate this gene represents a major step forward in developing new treatments for chronic illnesses such as cardiovascular diseases and diabetes, which are increased as a consequence of obesity. Diet and exercise are both important in weight loss. But individual response to diet and exercise vary dramatically – something that has long perplexed medical professionals.

“Weight loss, especially among people who are dieting, is affected by several factors and we’ve long suspected that personal genetic makeup is a real influence. We are learning that genes which make you fat are not the same as the genes that help you lose weight. And now we can put our finger on just how the weight-loss gene is activated,” said Alexandre Stewart, PhD, principal investigator of the Ruddy Canadian Cardiovascular Genetics Research Centre, UOHI.

The UOHI research is expected to lead to the development of therapies to fuel ACLS5 activity in people. Further, medical professionals will be able to identify people who won’t respond to diet and target drug treatment to help them lose weight more quickly.

Details of the latest UOHI discovery were published online in the Journal of the Federation of American Societies for Experimental Biology (http://www.fasebj.org/cgi/content/abstract/fj.08-120998v) The research was undertaken by molecular biologists at UOHI’s Ruddy Canadian Cardiovascular Genetics Centre, led by Alexandre Stewart, PhD, and Frederique Tesson, PhD.

UOHI scientists found that the people who carry the ACSL5 DNA variant are able to lose weight faster when following a low calorie diet than those who do not. About 33% Caucasians carry this genetic variant, as do 50% of Blacks, and 29% of Orientals.

Obesity and weight-related illness have been the focus of major scientific projects at UOHI and is part of a global drive to fight obesity. One UOHI research team led by Dr. Ruth McPherson has been investigating the genetics behind obesity – considered a serious risk factor for coronary artery disease. They are searching for patterns among obese people to help explain why one obese person suffers from heart disease or diabetes when an equally heavy person does not.

“We know that controlling obesity is hugely important in managing serious chronic disease such as heart disease and diabetes. But clearly we also know the problem is much more complex than just teaching people how to eat better and get more exercise. We need to understand the genetics and biology of obesity in order to individualize treatment,” said Dr. McPherson, Director of the Lipid Clinic, UOHI.

Source: Ottawa Heart Institute, University of Ottawa




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