Understanding why you can't stop at eating just one potato chip

Have you ever sat with a bag of chips with theidea of just trying a handful and saving the rest, but ended up licking theentire packet clean? If so, you may soon find out the explanation.

High-calorie foods-high in fat, oil, andsugar-can taste good but often cause overeating, leading to obesity and majorhealth problems. But what stimulates the brain to cause overeating?

Recently, it has become clear that a genecalled CREB-Regulated Transcription Coactivator 1 (CRTC1) is associated withobesity in humans. When CRTC1 is deleted in mice, they become obese, indicatingthat functioning CRTC1 suppresses obesity. However, since CRTC1 is expressed inall neurons in the brain, the specific neurons responsible for suppressingobesity and the mechanism present in those neurons remained unknown.

To elucidate the mechanism by which CRTC1suppresses obesity, a research group led by Associate Professor ShigenobuMatsumura from the Graduate School of Human Life and Ecology at OsakaMetropolitan University focused on neurons expressing the melanocortin-4receptor (MC4R). They hypothesized that CRTC1 expression in MC4R-expressingneurons suppressed obesity because mutations in the MC4R gene are known tocause obesity. Consequently, they created a strain of mice that expresses CRTC1normally except in MC4R-expressing neurons where it is blocked to examine theeffect that losing CRTC1 in those neurons had on obesity and diabetes.

When fed a standard diet, the mice withoutCRTC1 in MC4R-expressing neurons showed no changes in body weight compared tocontrol mice. However, when the CRTC1-deficient mice were raised on a high-fatdiet, they overate, then became significantly more obese than the control miceand developed diabetes.

"This study has revealed the role that the CRTC1gene plays in the brain, and part of the mechanism that stops us fromovereating high-calorie, fatty, and sugary foods," said Professor Matsumura."We hope this will lead to a better understanding of what causes people toovereat."

Reference:

Shigenobu Matsumura et al,CRTC1 deficiency,specifically in melanocortin-4 receptor-expressing cells, induces hyperphagia,obesity, and insulin resistance,The FASEB Journal,DOI: 10.1096/fj.202200617R