Continuing a high-calorie diet can create barriers to weight loss

Continuing a high-calorie diet can create barriers to weight loss

If you can’t keep your mouth shut when losing weight, it may be because your brain cells are “accustomed” to getting fat. On November 2, the international academic journal “Science Advances” published a study by Professor Wang Hao’s team from the School of Brain Science and Brain Medicine at Zhejiang University and found that under the condition of continuous high-calorie diet, the neurons that suppress appetite – the central aqueduct gray matter area (PAG) GABAergic neurons will “strike”.

“High-calorie foods not only affect weight and metabolism, but may also cause changes in the central nervous system.” Wang Hao said that to a certain extent, the brain will adapt to the body’s obesity state and prevent it from returning to the pre-obesity body shape.

Lack of self-discipline in weight loss may be affected by brain cells

The operation of life generally follows the principles of balance and moderation. In 2019, Wang Hao’s team discovered that GABAergic neurons, a nucleus in the central aqueductal gray area (PAG) of the brain, have the function of suppressing appetite. Brain cells mainly include neurons and glial cells. When people eat, brain cells containing GABAergic neurons will remind “don’t eat too much.”

The hypothalamus is the center of human feeding behavior. AgRP-positive neurons in the lateral hypothalamus and arcuate nucleus can sense “hungry” and thus trigger foraging behavior. Wang Hao said that the GABAergic neurons in the central aqueduct gray matter are the downstream nuclei of the hypothalamus. When the upstream hypothalamus feels “hungry”, this group of neurons responds and performs “responsibility” for supervision.

In modern society, high-calorie foods are becoming increasingly abundant, and the incidence of obesity is increasing year by year. Although some studies have shown that weight can be controlled by changing diet and lifestyle habits, there is a chance that weight will rebound. In response to this phenomenon, the team tried to find the basis for the changes that high-calorie foods have on the brain.

In this study, researchers divided a group of standard-weight mice into two groups. One group was fed regular food, and the other group was fed high-calorie food with twice the calories of regular food. After 6-8 weeks, the weight of the mice in the high fever group increased by 25%. To their surprise, GABAergic neurons in the central aqueductal gray matter (PAG) of mice were strongly inhibited after being fed high-calorie food for about 1 week.

Wang Hao explained that before the weight of the mouse changed, its brain had already changed, and the neurons responsible for suppressing appetite “strike.” This phenomenon occurs, on the one hand, because the upstream brain areas increase the inhibition of this group of brain cells, and on the other hand, because the intrinsic excitability of these neurons themselves also decreases. Without the “supervision” of this group of brain cells, the mice became addicted to food and could not extricate themselves.

Potential target discovered to treat refractory obesity

Can mice fed a high-calorie diet still hope to lose weight successfully?

Another set of research by Wang Hao’s team provided important clues: using single-cell nuclear transcriptome sequencing technology, it was found that compared with ordinary mice, the expression of the CACNA2D1 gene in GABAergic neurons in the “eating inhibitory” nucleus of obese mice was significantly higher lower.

Using transgenic adenovirus technology, researchers increased the expression of the CACNA2D1 gene on GABAergic neurons of obese mice and found that even when faced with the same high-calorie food as usual, the obese mice’s food intake decreased, and their body weight and body fat levels were reduced. All decreased, and slowly lost weight again.

“It should be pointed out that the changes in the brain caused by high-calorie diet are acquired and caused by high-calorie diet for a specific period of time.” Wang Hao said that the increase in CACNA2D1 gene expression on the one hand reduced the food intake of mice, and on the other hand On the one hand, it also improves its metabolic level. This makes CACNA2D1 a potential target for treating refractory obesity. “If we can discover molecules that can effectively activate this gene, it may be possible to screen potential weight loss drugs.” (Hong Hengfei, Zhou Wei, our reporter Jiang Yun)

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