Knowing that you will be fat and want to eat, the team of Zhou Yudong/Shen Yi of Zhejiang University reveals the neuroinflammatory mechanism of compulsive eating

Why you can't control the urge to eat even though you know that eating too many high-calorie foods will make you fat? Maybe your brain is "inflamed"
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Recently, Zhou Yudong/Shen Yi's research group from Zhejiang University published a research paper entitled: Diet-induced Inflammation in the Anterior Paraventricular Thalamus Induces Compulsive Sucrose-seeking in the journal Nature Neuroscience
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This study revealed the neuroinflammatory mechanism of high-fat diet (HFD)-induced compulsive eating, and found that high-fat food increased the proliferation of microglia in the anterior paraventricular nucleus of the thalamus (aPVT), resulting in abnormal function of aPVT excitatory neurons, and then compulsive eating behavior
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Obsessive-compulsive eating behaviors are typically characterized by choosing to obtain food despite knowing the risk
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In order to evaluate the compulsive-like behavior of mice on a high-fat diet, the researchers first conducted operant conditioning training in the mice, that is, in a Skinner box, to establish operant conditioning for mice to press a lever once to receive a small spoonful of sugar water as a reward , and then add the classic conditioned reflex of fear on this basis, that is, when mice see the light flashing in the box, they will associate the fear of foot shock
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During the test, there is a 50% probability that the mouse's rod-pressing behavior will flash the light, which means that the mouse may be shocked by the rod-pressing behavior
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When the lure of sugar water and the fear of foot shock coexist, what choice will mice make? The researchers found that normal mice suffered a sharp drop in rod-pressing behavior due to fear of being electrocuted, while mice on a high-fat diet continued to press the rod for the sugar-water reward
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Why does a high-fat diet lead to compulsive eating behavior? The researchers used c-fos staining to screen for abnormal activation of CaMKIIα neurons in the anterior paraventricular nucleus of the thalamus (aPVT) in HFD mice
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PVT acts as a "signal processor" in the brain
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Using the method of in vivo calcium imaging, the changes of calcium signal in aPVT neurons of mice were recorded during the forced rod pressing
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The results showed that the calcium signal of this group of aPVT neurons was significantly enhanced when and only when the light flashed in the pressure-bar situation, suggesting that aPVT neurons are crucial in processing danger signals
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Next, the research team regulated the activity of aPVT neurons by means of optogenetics and pharmacogenetics, and found that activating aPVT neurons can cause compulsive eating behavior in normal mice, while inhibiting aPVT neurons can effectively reduce the high-fat diet.
Emergence of compulsive-like behavior in mice
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These results show that high-fat food can induce compulsive-like eating by affecting the activity of aPVT neurons
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At the same time, the research team also found that the expression of the microglia marker Iba-1 in the aPVT brain region of the high-fat diet mice increased, indicating that high-fat intake caused an inflammatory response in the aPVT brain region
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So is the abnormal function of aPVT neurons related to microglial activation? Does inhibiting the activation of microglia induced by a high-fat diet reduce the appearance of compulsive-like behaviors?
To this end, the research team used two methods, one is to add the colony-stimulating factor 1 receptor (CSF1R) inhibitor PLX3397 to food, and the other is to inject anti-CSF1 antibody to aPVT to inhibit the growth of microglia.
It was found that both methods can effectively reduce compulsive-like behavior, indicating that high-fat food induces compulsive-like behavior by activating microglia in the aPVT brain region, suggesting that a certain degree of anti-inflammatory may reduce the desire to eat and eat.
impulsive
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In short, the study shows that a high-fat diet causes microglia activation and neuronal dysfunction in the paraventricular nucleus of the anterior thalamus, leading to compulsive-like eating behavior, which increases high-fat food intake, This creates a vicious circle that eventually leads to obesity
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Of course, there are still some issues that have not yet been elucidated, such as the neural circuits involved in compulsive eating behavior, how microglia activation affects the activity of thalamic neurons, and the role of fatty acids on thalamic neurons
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In an era of scarcity of food, life can be maintained only by ingesting and storing calories in a timely manner.
As a result, the corresponding brain has also evolved to control the body's eating behavior, making the body prefer high-calorie foods
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Nowadays, high-calorie foods are everywhere and easily available.
The original brain has not yet fully adapted to the current food environment, and still instructs our body to continuously consume high-calorie foods
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Excessive intake of high-calorie foods puts the brain in a state of chronic inflammation, and neuronal dysfunction related to food intake and reward leads to compulsive eating, which is one of the important reasons for the increase in obesity rates today
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Doctoral students Cheng Jingjing, Ma Xiaolin and postdoctoral fellow Li Chunlu of Zhejiang University School of Medicine are the co-first authors of the paper, and Professor Zhou Yudong and Associate Professor Shen Yi are the co-corresponding authors
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This project is funded by the National Key Research and Development Program of the Ministry of Science and Technology "Developmental Programming and Its Metabolic Regulation" and the National Natural Science Foundation of China
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