Genetic mechanism associated with high-calorie food-fueled obesity revealed

Gene identified to explain 'one-chip, unstoppable' phenomenon

Researchers at Tokyo Metropolitan University found that the transcriptional cofactor gene CRTC1 mediates the anti-obesity effects of the melanocortin-4 receptor (MC4R) by regulating appetite for fat, high-fat diet metabolism, and blood sugar. clarified. credit: FASEB Journal (2022). DOI: 10.1096/fj.202200617R

High-calorie foods high in fat, oil, and sugar may taste great, but they often lead to overeating, leading to obesity and other serious health problems. But what stimulates the brain to cause overeating?

Recently, a gene called CREB-Regulated Transcription Coactivator 1 (CRTC1) was found to be associated with obesity in humans. Deletion of CRTC1 in mice leads to obesity, showing that functional CRTC1 suppresses obesity. However, since CRTC1 is expressed in all neurons in the brain, the specific neurons that suppress obesity and the mechanisms underlying these neurons remained unclear.

To elucidate the mechanism by which CRTC1 suppresses obesity, a research group led by Associate Professor Shigenobu Matsumura of the Graduate School of Life Sciences, Tokyo Metropolitan University focused on neurons that express melanocortin-4 receptors (MC4R).

They hypothesized that CRTC1 expression in MC4R-expressing neurons suppressed obesity, as mutations in the MC4R gene are known to cause obesity. As a result, they created a strain of mice that normally expressed CRTC1, but in these neurons, unless CRTC1 was blocked in these neurons, and he found that loss of CRTC1 had an effect on obesity and diabetes. I checked.

Mice lacking CRTC1 in MC4R-expressing neurons showed no change in body weight compared with control mice when fed a standard diet. However, when CRTC1-deficient mice were fed a high-fat diet, they overeat, became significantly more obese than control mice, and developed diabetes.

“This study sheds light on the role the CRTC1 gene plays in the brain and some of the mechanisms that prevent overeating of foods high in calories, fat and sugar,” said Matsumura. “I hope this leads to a better understanding of what causes people to overeat.”

Research results published in a journal FASEB Journal.

For more information:
Shigenobu Matsumura et al. CRTC1 deficiency, especially in melanocortin-4 receptor-expressing cells, induces hyperphagia, obesity, and insulin resistance. FASEB Journal (2022). DOI: 10.1096/fj.202200617R

Provided by Tokyo Metropolitan University

Quote: Genetic Mechanisms Associated with High-Calorie Food-Fueled Obesity Revealed (December 23, 2022) obesity.html

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