Auto-Antibodies Promote Obesity

This post is NOT about people who have antibodies to cars.

It is about the intriguing new finding that some people with obesity may have circulating antibodies that neutralize important brain receptors involved in energy regulation, thereby blocking key signaling mechanisms involved in eating behaviours such as satiety.

This at least is the jist of a paper by Jean-Christophe Peter and colleagues from the University of Basel, Switzerland, published in the latest issue of the Journal of Clinical Endocrinology & Metabolism.

The researchers screened blood samples from 216 probands and found auto-antibodies directed against the melanocortin-4 receptor (MC4R) in around 4% of the obese participants but in none of the normal-weight subjects.

Readers of these pages may recall that the MC4R is a key receptor in mediating satiety signals and that mutations of this receptor are the most common cause of monogenic obesity in the population (about 5-6% of patients with severe obesity have an MC4R mutation).

The auto-antibodies not only bind to the MC4R but also block its function. When these receptors were isolated from human blood samples, purified and injected into rats, they dramatically increased food intake.

These observations suggest that in some patients with excess weight, inhibitory anti-MC4R auto-antibodies might contribute to the development of obesity.

Not only do these studies again point to the importance of the MC4 pathway for energy homeostasis but suggest a novel mechanism for obesity that may go beyond genetic mutations in this system.

AMS
Edmonton, Alberta