Study finds how CRTC1 gene is associated with obesity in humans

OSAKA: High-calorie, high-fat, high-sugar foods can taste nice but can contribute to overeating, obesity, and other serious health issues. But what triggers overeating in the brain?

It has recently become evident that the human gene CREB-Regulated Transcription Coactivator 1 (CRTC1) is linked to obesity. Mice lacking CRTC1 develop obesity, which suggests that CRTC1 in normal operation prevents obesity.

The precise neurons that reduce obesity and the mechanism they contain are yet unclear, though, because CRTC1 is found in all brain neurons.

To elucidate the mechanism by which CRTC1 suppresses obesity, a research group led by Associate Professor Shigenobu Matsumura from the Graduate School of Human Life and Ecology at Osaka Metropolitan University focused on neurons expressing the melanocortin-4 receptor (MC4R).

They hypothesized that CRTC1 expression in MC4R-expressing neurons suppressed obesity because mutations in the MC4R gene are known to cause obesity.

Consequently, they created a strain of mice that expresses CRTC1 normally except in MC4R-expressing neurons where it is blocked to examine the effect that losing CRTC1 in those neurons had on obesity and diabetes. When fed a standard diet, the mice without CRTC1 in MC4R-expressing neurons showed no changes in body weight compared to control mice.

However, when the CRTC1-deficient mice were raised on a high-fat diet, they overate, then became significantly more obese than the control mice and developed diabetes.

"This study has revealed the role that the CRTC1 gene plays in the brain, and part of the mechanism that stops us from overeating high-calorie, fatty, and sugary foods," said Professor Matsumura. "We hope this will lead to a better understanding of what causes people to overeat."