We all know that long-term stress can lead to a series of physical and mental health problems, such as anxiety, depression and other negative emotions, as well as appetite disorders, weight disorders and other metabolic problems. Many people in the face of stress, will show emotional eating (emotional eating), that is, by eating too much to relieve the negative emotions caused by stress. Emotional eating is often accompanied by excess calories, which is one of the risk factors for obesity. So, what is the mechanism through which stress causes appetite disorders? What is the relationship between tryptophan metabolism and stress-induced emotional eating? To solve these problems, researchers have carried out a series of detailed explorations.

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Tryptophan is one of the essential amino acids in the human body and the precursor of the neurotransmitter 5-hydroxytryptophan (5-HT, also known as serotonin) in the brain. A large number of studies have shown that tryptophan metabolism disorders are closely related to a variety of mental diseases, such as depression, anxiety, schizophrenia and so on. At the same time, tryptophan and its metabolite 5-HT are also involved in the regulation of appetite and energy balance. So, under chronic stress conditions, does tryptophan metabolism change? Is this change related to abnormal stress-induced eating behavior? With these questions in mind, the researchers conducted a series of detailed experiments.

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First, the researchers used mice to develop a chronic stress-induced emotional eating model (CMS). They subjected the mice to a variety of mildly unpredictable stresses, such as confinement stress, shaking cages, and cold water baths, for 21 consecutive days to simulate persistent, diverse stressors in real life. The results showed that after 21 days of chronic stress, the mice exhibited significant anxiety and depression-like behavior. In the open field experiment (OFT), the time of CMS group mice staying in the central area of open field was significantly shortened, indicating that their anxiety level was increased. In the tail hanging experiment (TST), the struggle time of mice in the CMS group was significantly shortened, suggesting an increased sense of hopelessness. At the same time, the food intake of mice in CMS group increased significantly, but the weight decreased significantly, suggesting that their appetite and metabolism were disturbed.

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Subsequently, the researchers performed a targeted metabolomic analysis of the tryptophan metabolic pathway in mouse serum. The results showed that the serum tryptophan content of CMS group mice was significantly decreased, while the downstream metabolites 5-hydroxytryptamine (5-HT) and kynurenine contents were significantly increased. Further analysis showed that the mRNA expression of tph1, a key enzyme in the synthesis of 5-hydroxytryptamine, was significantly down-regulated in the colon tissue of mice in CMS group, and the content of 5-HT in colon also showed a downward trend. This suggests that chronic stress disrupts the homeostasis of the tryptophane-5-HT metabolic pathway in the intestinal tract of mice, resulting in an imbalance of peripheral 5-HT levels.

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Although tryptophan cannot directly pass the blood-brain barrier, its metabolite 5-HT plays an important role as a neurotransmitter in the central nervous system and is involved in regulating many physiological processes such as mood, cognition and eating. The researchers further analyzed changes in the expression of several neuropeptides and 5-HT receptors involved in appetite regulation in the hypothalamus. The results showed that chronic stress significantly upregulated the expression of appetitepromoting neuropeptides such as AgRP and OX1R, while downregulated the expression of appetiteinhibiting factors such as LEPR, MC4R and 5-HT1B. This suggests that the disturbance of tryptophane-5-HT pathway may lead to abnormal feeding behavior by affecting the hypothalamic neural circuit.

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So, can supplementation with tryptophan relieve chronic stress-induced mood and eating behavior abnormalities? Two doses of tryptophan (100mg/kg and 300mg/kg) were administered to CMS mice by daily gavage for 21 days. The results showed that after 21 days of intervention with a high dose of tryptophan (300mg/kg), the anxiety and depression-like behavior of mice in open field experiment and tail suspension experiment was significantly improved, and abnormal increased food intake and weight loss were corrected. Further studies have shown that high-dose tryptophan intervention can inhibit the up-regulation of appetite promoting factors such as AgRP and OX1R in hypothalamus induced by chronic stress, while restoring the expression of appetite inhibiting factors such as LEPR, MC4R, 5-HT1B and 5-HT2C. It is worth noting that although the low dose of tryptophan (100mg/kg) group did not show significant improvement in behavioral indicators, there was a trend of changes in hypothalamic appetite related gene expression at the molecular level.

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Further molecular mechanism studies have shown that 5-HT, by binding 5-HT1B and 5-HT2C receptors on hypothalamic POMC, AgRP and other neurons, inhibits the AgRP/NPY neurons that promote appetite, activates POMC neurons that inhibit appetite and promote energy consumption, and then plays a role in regulating appetite and weight. This provides important molecular mechanism support for the improvement of emotional feeding by tryptophan-5-HT pathway.

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The researchers also used the mouse hypothalamic neuron cell line GT1-7 to further verify the regulatory effect of 5-HT on appetite related neuropeptides. They treated GT1-7 cells with 10μM of corticosterone (CORT) for 24 hours to simulate chronic stress conditions. The results showed that the expression of appetite promoting genes such as AgRP and OX1R was significantly up-regulated by CORT treatment, while the expression of appetite inhibiting genes such as MC4R, 5-HT1B and 5-HT2C was down-regulated. After pretreatment with 0.1μM 5-HT for 2 hours, the abnormal expression of CORt-induced AgRP and other genes could be significantly reversed, and the expression of MC4R, 5-HT1B and 5-HT2C could be restored. This further confirmed the direct regulatory effect of 5-HT on hypothalamic neurons.

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Data summary:

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Effects of chronic stress on tryptophan metabolism homeostasis in mice: Chronic stress caused serum tryptophan levels to decrease (P<0.05), while 5-HT and kynuuric acid levels to increase (P<0.01). ELISA results showed that the level of 5-HT in the colon of mice with chronic stress decreased (P<0.01), suggesting that chronic stress disrupted the tryptophan /5-HT metabolic pathway in mice.

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Effect of tryptophan on appetite and depression-like behavior induced by chronic stress: High-dose tryptophan supplementation restored abnormal eating behavior and weight loss induced by chronic stress (P<0.01) and improved anxiety and depression-like behavior in mice (P<0.05). In the open field test, the desire to explore was significantly increased in the high-dose tryptophan supplement group (P<0.05), and the desperate behavior was significantly decreased in the tail suspension test (P<0.05).

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Effects of tryptophan supplementation on hypothalamic feeding neurons and appetite regulators in chronic stress mice: Immunohistochemical staining showed that the expression of c-fos and AgRP in ARC region of hypothalamus in chronic stress group was significantly increased, while the expression of LEPR was significantly decreased (P<0.01). After high-dose tryptophan supplementation, AgRP expression decreased (P<0.05), LEPR expression increased (P<0.05). The qPCR results showed that tryptophan supplementation significantly decreased the mRNA expression levels of AgRP and OX1R in the hypothalamus of chronic stress mice (P<0.01), and increased the mRNA expression levels of MC4R and LEPR in the hypothalamus of chronic stress mice (P<0.01).

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Effects of tryptophan on 5-HT metabolic pathway in hypothalamus of chronic stress mice: Serum tryptophan and 5-HT levels were significantly increased after tryptophan supplementation (P<0.05), but there was no significant difference in 5-HT content in colon and cerebral cortex. The results of RT-qPCR showed that tryptophan supplementation significantly increased the mRNA expression level of tph1 in colon (P<0.05), tph2 in hypothalamus (P<0.01), and 5-HT1B and 5-HT2C receptor expression levels (P<0.01).

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Overall, this study reveals that chronic stress causes disruption of the hypothalamic appetite regulatory network by disrupting the tryptophane-5-HT metabolic pathway, which in turn triggers emotional eating. Supplementation of exogenous tryptophan, especially in high doses (300mg/kg), restores central 5-HT levels, activates hypothalamic 5-HT1B and 5-HT2C receptors, inhibits AgRP/NPY neurons, activates POMC neurons, and improves stress-related mood disorders and abnormal eating behaviors.

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This research result has important practical significance. In today's fast-paced, high-stress life, many people are faced with stress-induced emotional issues and weight disorders. Studies have shown that long-term stress causes the body's tryptophan level to decline, 5-hydroxytryptamine synthesis to decrease, and then lead to a series of neuroendocrine disorders, leading to depression, anxiety and other negative emotions, as well as hyperappetite, obesity and other metabolic problems. This study reveals the central role of tryptophan and its metabolite 5-hydroxytryptophan in the stress-emotion-appetite regulation axis, providing new ideas and methods for relieving stress and improving mood disorders and weight disorders.

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Based on the findings, the researchers offer some dietary recommendations to help people cope better with stress. First of all, the proper supplement of tryptophan rich foods in the daily diet, such as eggs, cheese, nuts, bananas, oats, etc., can help improve the level of tryptophan in the body, promote the synthesis of 5-hydroxytryptophan, thereby improving the emotional state and inhibiting stress eating. However, it should be noted that tryptophan in food is not 100% absorbed and utilized. At the same time, long-term large dose supplementation of tryptophan (such as more than 500mg/kg) may cause kidney damage. Therefore, in the daily diet balance, moderate supplement of tryptophan can be, do not advocate excessive use of tryptophan supplements.

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In addition, moderate exercise such as jogging, swimming, yoga, etc., can also help increase the level of tryptophan and serotonin synthesis in the body, relieve stress and improve mood. Getting enough sleep, developing a positive and optimistic attitude, and learning to express emotions reasonably are all effective ways to cope with stress. When facing serious emotional problems such as depression and anxiety, it is necessary to seek professional psychological treatment in time.

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In conclusion, this study reveals the mechanism of emotional eating induced by chronic stress from the perspective of tryptophan metabolism, and provides a new perspective for relieving stress, improving mood disorders and weight disorders. Although further population studies are needed to optimize the dosage and duration of tryptophan supplementation in the diet, the results of this study have provided us with new ideas for promoting physical and mental health through dietary regulation. We believe that through a balanced diet, moderate exercise, good sleep and positive emotional coping, we can more calmly face the pressure of life and embrace a better future.