Wu Qi's team at Baylor College of Medicine in the United States reported a novel neural circuit regulation mechanism and targeted combination therapy for the co-occurrence of obesity and anxiety and depression

A large number of clinical studies have shown that obese patients often suffer from mental illnesses such as bioon.
com/tags/%E6%8A%91%E9%83%81%E7%97%87/" target="_blank">depression and anxiety at the same time .
Recently, the Wu Qi team and collaborators of Baylor College of Medicine in the United States published a paper in Molecular Psychiatry, a top neuroscience journal under the Nature Springer Publishing Group, providing new breakthrough insights into this association.
They successfully discovered and explained a new neural circuit mechanism and targeted combination medication regimen for bidirectional regulation of feeding behavior and mental state.

It is reported that approximately 43% of adults with bioon.
com/tags/%E6%8A%91%E9%83%81%E7%97%87/" target="_blank">depression also suffer from obesity, and adults with mental illness are more likely to be obese than adults with mental health.
Similar to human patients, mice that have long-term intake of high-fat foods become not only obese, but also have obvious symptoms of anxiety and depression.
The Wu Qi group proposed for the first time that this highly co-occurring pathological phenomenon is caused by the dysfunction of a specific brain circuit.
Through a series of bioon.
com/course_video/zhong-guo-ren-qun-ying-yang-he-yi-chuan-yin416058.
html">genetic After correcting defects in the function of the loop by the high-fat diet produced chemical or pharmacological methods, the group researchers first found that anxiety and bioon.
com/tags/%E6%8A%91%E9%83%81%E7%97%87/" target="_blank">depression -like disappeared completely, and then surprised to find that the food intake of animals is strongly Inhibition, and eventually lead to obesity symptoms are almost completely eliminated.
More interestingly, the weight loss produced here is not due to loss of appetite, but because the animals actively reduce their preference for high-fat foods.
Similar to humans, rodents, including mice, generally have a high preference for high-fat foods.
However, after intervention in this neural circuit, the food preferences of the mice actively turned to a healthy diet with a lower fat content and rich in protein and carbohydrates.
This discovery explains for the first time the co-occurrence mechanism of obesity and mental illness and reveals the possibility of targeted drug therapy for it.

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In order to explore the neural circuits that can regulate weight gain and depression or anxiety in both directions, the research team provided mice with a high-fat diet, and the mice not only developed the expected symptoms of obesity, but also developed anxiety and depression at the same time.
In a series of studies conducted on this obese mouse model, Professor Wu’s team discovered a new type of neural circuit composed of two groups of neurons located in different brain regions, including the dorsal stria terminalis nucleus (dBNST) Melanocortin receptor 4 (MC4R) neurons and agouti peptide-related protein (AgRP) neurons located in the arcuate nucleus (ARC) of the hypothalamus.

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Conducive to real-time neuroimaging and multi-channel electrophysiology and other technical means, we found that this neural circuit has different degrees of functional disorder in obese and depression mouse models.
Using optical targeting transgene and bioon.
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html">genetic methods like science, we obesity and bioon.
com/tags/%E6%8A%91%E9%83%81%E7%97%87/" target="_blank">depression identified and participate in a group mediating specific gene function deficient mice neural circuit model.

More importantly, we found that after correcting the defects in the neural circuit to a normal state, the anxiety and depression caused by a high-fat diet can be effectively eliminated, and then the food intake and weight can be significantly reduced.
To our surprise, the weight loss was not because the animals completely lost appetite, but by bioon.
com/course_video/zhong-guo-ren-qun-ying-yang-he-yi-chuan-yin416058.
html">genetic adjust the mental state after school or pharmacological methods, effectively correct dietary preferences, that the initiative to change from the original preference for high-fat food Healthier low-fat foods.

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Taking into account the potential and application prospects of this important discovery in clinical medicine, we extensively screened and explored the possibility of combined drug therapy to correct the functional defect of this neural circuit through bioon.
com/course_info/series_11.
html">genomics and pharmacological methods.
We finally found that a targeted combination drug therapy consisting of Zonisamide and Granisetron can completely eliminate the synergistic effect produced by acting on two different signaling pathways in the newly discovered neural circuit.
Symptoms of anxiety and depression in turn made animals tend to eat healthier, low-fat foods, and ultimately significantly corrected the symptoms of obesity and overweight.
The results of these trials reveal the high feasibility of cocktail therapy consisting of Zonisamide and Granisetron or its derivatives in the treatment of obesity and comorbid mental illness, and is a useful tool for further development of pathological pharmacology.
Research and large-scale clinical medical trials provide strong support in molecular and neurophysiological mechanisms and translational medicine.

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The corresponding author of this article is Professor Wu Qi from Baylor College of Medicine and the Child Nutrition Research Center of the United States Department of Agriculture.
He has won honorary titles such as Pew PEW Biomedical Scholar and Kavli Foundation Scholar.
The co-first authors of the paper are postdoctoral researcher Dr.
Xia Guobin and postdoctoral researcher Dr.
Han Yong.