Scientists reveal genetic mechanism linked with high-calorie food-fueled obesity

03 Jan 2023 --- High-calorie foods, such as those high in fat, oil and sugar, can taste good but often cause overeating, leading to obesity and major health problems. Now researchers from the Osaka Metropolitan University in Japan have investigated what stimulates the brain to cause overeating and discovered a genetic mechanism associated with high-calorie, food-fueled obesity.

The research results have been published in the FASEB Journal. 

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

When CRTC1 is deleted in mice, they become obese, indicating that functioning CRTC1 suppresses obesity. However, since CRTC1 is expressed in all neurons in the brain, the specific neurons responsible for stopping obesity and the mechanism present in those neurons remains unknown.

To explain 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). 

The researchers 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 typically except in MC4R-expressing neurons where it is blocked to examine the effect that losing CRTC1 in those neurons had on obesity and diabetes.High-calorie foods, such as those high in fat, oil and sugar, can taste good but often cause overeating, leading to obesity.

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, 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,” says Professor Matsumura. 

“We hope this will lead to a better understanding of what causes people to overeat.”

Research into obesity
Ultra-processed foods continue to be in the spotlight for several health reasons. In November, a total of 57,000 premature deaths in Brazil were attributed to the consumption of ultra-processed foods in 2019, according to research published in the American Journal of Preventive Medicine.

Meanwhile, last month, new research delved into the benefits of almonds regarding weight management and addressed the multifaceted challenge of being overweight and obesity. 

In other developments, amid concerns the UK government will scrap recently-introduced health and nutrition policies, researchers are increasingly worried the country is losing its focus on dietary advice and how vital it is to stem obesity.

Edited by Elizabeth Green

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