New research links metabolism and appetite suppression, opening door to obesity treatments

A team led by a Canadian researcher has discovered a process by which a small protein acts directly within muscles to increase the body's metabolism to burn fat while simultaneously suppressing appetite. These findings suggest that the protein, known as the ciliary neurotrophic factor (CNTF), could play a key role as a weight loss agent.

Until recently, most obesity research has focused on the regulation of appetite by hormones such as leptin. Research led by Dr. Greg Steinberg - a Target Obesity fellow funded by the Heart and Stroke Foundation of Canada, the Canadian Institutes of Health Research, and the Canadian Diabetes Association - demonstrates that CNTF protects against some of the effects of obesity.

It does this by activating an enzyme, skeletal muscle AMP kinase, which increases the ability of the body to metabolize fat and sugar. This work may lead to new strategies to reduce the risk of metabolic abnormalities associated with excess weight.

Dr. Steinberg's research shows how CNTF activates similar pathways to those stimulated by exercise.

"While hormones such as leptin were initially thought to be the cure-all for weight loss, they were later found to be ineffective in obesity due to the presence of proteins which inhibit their ability to stimulate fat metabolism," says Dr. Steinberg, a Canadian researcher at the University of Melbourne, Australia. "Fortunately, CNTF's effects on fat burning are maintained."

Nearly half of all adult Canadians are overweight or obese and 26 per cent of Canadian children and adolescents aged two to 17 are overweight or obese. From 1985 to 2000, 57,000 deaths in Canada were associated with overweight and obesity.

"The incidence of obesity in Canada has more than doubled over the course of the last 20 years and is a major contributor to cardiovascular risk factors including diabetes and elevated blood fats," says Dr. Ruth McPherson, Heart and Stroke Foundation spokesperson and lipid expert. "Physical activity and healthy diet are important lifestyle factors in combating obesity. This study provides new clues on the regulation of skeletal muscle metabolism relevant to the treatment of obesity."

"Dr. Steinberg's finding is significant because this new pathway that overcomes leptin resistance opens the door to a more promising avenue for the development of a therapeutic anti-obesity agent," says Dr. Diane Finegood, scientific director of the Canadian Institutes of Health Research Institute of Nutrition, Metabolism and Diabetes.

"This research is an important step in the unravelling of the complex biological systems controlling body weight, including mechanisms regulating blood sugar levels, food intake, and satiety - a feeling of fullness - which are crucial to tackling the worldwide epidemic of obesity," adds Dr. Finegood.

"Carrying extra weight is a risk factor for type 2 diabetes, and 80% of people with diabetes struggle with excess weight. This study offers early yet encouraging findings for people affected by the condition," says Dr. Paula Dworatzek, Sr. Research Associate, Canadian Diabetes Association.

Obesity is a major contributor to heart disease, type 2 diabetes, hypertension, stroke, and some cancers. Solutions that address the many factors contributing to obesity are needed.

Target Obesity, a research initiative investigating the behavioural, biological, and societal determinants of obesity, is led by the Heart and Stroke Foundation of Canada, in partnership with the Canadian Institutes of Health Research and the Canadian Diabetes Association.

Obesity treatments from neurotrophic (or nerve nourishing) factors such as CNTF are several years away but this research opens the door to further studies.

Dr. Steinberg's study, "CNTF reverses obesity-induced insulin resistance by activating skeletal muscle AMPK," is published by Nature Medicine and the abstract is now available online.