HQ Team
December 26, 2022: Processed foods rich in fat, sugar and oil are difficult to resist as they appeal to the taste buds and fulfil cravings but are often the cause of ill health and obesity.
Research has shown that a particular gene—CREB- CREB-Regulated Transcription Coactivator 1 (CRTC1) is associated with obesity in humans. This gene is the one that controls overeating. However, since CRTC1 is present in all neurons in the brain, the exact way these neurons and genes function for obesity remains unknown.
To find out how CRTC1 works in 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).
MC4R codes for a protein called melanocortin 4 receptor, which is mainly found in the hypothalamus of the brain, an area responsible for controlling appetite and satiety. Human body has many sensors for energy levels. When it senses high energy levels, it sends out “satiety signals” to activate the neurons through the MC4R to alert the body that it’s full. When the body is low in energy, “hunger signals” activate the neurons again through MC4R.
The team premised that CRTC1 expression in neurons with MC4R suppressed obesity because mutations in 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 is blocked to examine the effect that losing CRTC1 in those neurons had on obesity and diabetes.
When fed a standard diet, mice without CRTC1 in MC4R-expressing neurons showed no changes in body weight compared to the 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,” said Professor Matsumura. “We hope this will lead to a better understanding of what causes people to overeat.”
One common variant of the MC4R gene, carried by 22% of the general population, causes reduced MC4R protein levels in the hypothalamus of the brain. Carriers of this variant have both increased appetite and decreased satiety. They tend to eat larger amounts of food, snack more frequently and like to eat fatty foods. Studies have shown that each copy of the variant is responsible for a BMI (Body Mass Index) increase of 0.22 and an obesity risk increase of 8%.
The research results were published in the FASEB Journal.
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