Have scientists found the gene that keeps you thin? - study

Recently, it has become clear that a gene called CREB-Regulated Transcription Coactivator 1 (CRTC1) is associated with obesity in humans.

By JUDY SIEGEL-ITZKOVICH, Jerusalem Post, DECEMBER 23, 2022

https://www.jpost.com/health-and-wellness/nutrition/article-725654

Most people who like salty and sweet snacks find it’s almost impossible to eat just one potato chip or peanut and only one fancy donut on Hanukkah and then call it quits.

It’s not just a lack of self-control that causes this behavior; it’s also a gene. Recently, it has become clear that a gene called CREB-Regulated Transcription Coactivator 1 (CRTC1) is associated with obesity in humans.

Scientists say they may have found a skinny gene

When CRTC1 is deleted in mice, they become obese, indicating that functioning CRTC1 suppresses obesity – but since CRTC1 is expressed in all neurons in the brain, the specific nerves responsible 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 Prof. Shigenobu Matsumura from the Graduate School of Human Life and Ecology at Osaka Metropolitan University focused on neurons expressing the melanocortin-4 receptor (MC4R).

MC4R is a critical regulator of appetite and energy expenditure in rodents and humans and a deficiency causes hyperphagia (an extreme, unsatisfied drive to consume food), reduced energy expenditure, and impaired glucose metabolism, they wrote.

“CRTC1 expression in MC4R cells is required for metabolic adaptation to a high-fat diet with respect to appetite regulation. Our results revealed an important protective role of CRTC1 in MC4R cells against dietary adaptation.”

The study was published in the FASEB (Federation of American Societies for Experimental Biology) Journal under the title “CRTC1 deficiency, specifically in melanocortin-4 receptor-expressing cells, induces hyperphagia, obesity, and insulin resistance.”

CRTC1 expression in mice

The team hypothesized that CRTC1 expression in MC4R-expressing neurons suppressed obesity because mutations in the MC4R gene are known to cause obesity. 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, but when the CRTC1-deficient mice were raised on a high-fat diet, they ate too much, 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 Matsumura. “We hope this will lead to a better understanding of what causes people to overeat.”

“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,”
Associate Prof. Shigenobu Matsumura

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