An evolutionary survival mechanism that helped early humans avoid starvation could be behind the obesity epidemic in society today.

Starvation puts considerable stress on cells. The body responds with a mechanism that blocks fat from burning when the body is starving, injured or cold. This enables energy to be conserved so people can survive longer, potentially long enough to find more food. However, the stresses on cells from overeating are extremely similar to those caused by starvation. The body therefore responds to obesity with the anti-starvation mechanism, which will make it harder for people to lose weight.

Scientists have discovered the receptor key to understanding this process. The receptor for advanced glycation end (RAGE) binds to molecules involved in metabolic stress. RAGE receptors have been found to be present on human fat cells.

Mice that had the gene which coded for RAGE knocked out were able to keep a healthy weight, despite being fed a high-fat diet which made normal mice obese. Translating fat from mice that had RAGE knocked out into normal mice also prevented the normal mice from gaining weight. The scientists concluded that molecules binding to RAGE on fat cells prevent the breakdown of fat after metabolic stress.

Obesity is a major public health concern and a risk factor for a significant number of other diseases. Even after successful weight loss diets, patients sometimes struggle to maintain their healthy weight. A target drug for the RAGE receptor may therefore have clinical benefit as a treatment for weight loss.

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