High-calorie foods-;high in fat, oil, and sugar-;can taste good but often cause overeating, resulting in obesity and major health problems. But what stimulates the brain to cause overeating?

Recently, it has change into clear that a gene called CREB-Regulated Transcription Coactivator 1 (CRTC1) is related to obesity in humans. When CRTC1 is deleted in mice, they change into obese, indicating that functioning CRTC1 suppresses obesity. Nevertheless, since CRTC1 is expressed in all neurons within the brain, the precise neurons accountable for suppressing obesity and the mechanism present in those neurons remained unknown.

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 within 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’s blocked to look at the effect that losing CRTC1 in those neurons had on obesity and diabetes.

When fed an ordinary food regimen, the mice without CRTC1 in MC4R-expressing neurons showed no changes in body weight compared to manage mice. Nevertheless, when the CRTC1-deficient mice were raised on a high-fat food regimen, 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 within the brain, and a part of the mechanism that stops us from overeating high-calorie, fatty, and sugary foods,” said Professor Matsumura. “We hope this may result in a greater understanding of what causes people to overeat.”

Source:

Osaka Metropolitan University

Journal reference:

Matsumura, S., et al. (2022) CRTC1 deficiency, specifically in melanocortin-4 receptor-expressing cells, induces hyperphagia, obesity, and insulin resistance. The FASEB Journal. doi.org/10.1096/fj.202200617R.