The Regulatory Role of the Central and Peripheral Serotonin Network on Feeding Signals in Metabolic Diseases
Central and peripheral serotonin (5-hydroxytryptamine, 5-HT) regulate feeding signals for energy metabolism. Disruption of central 5-HT signaling via 5-HT2C receptors (5-HT2CRs) induces leptin-independent hyperphagia in mice, leading to late-onset obesity, insulin resistance, and impaired glucose to...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-01-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/3/1600 |
| _version_ | 1797487282879463424 |
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| author | Katsunori Nonogaki |
| author_facet | Katsunori Nonogaki |
| author_sort | Katsunori Nonogaki |
| collection | DOAJ |
| description | Central and peripheral serotonin (5-hydroxytryptamine, 5-HT) regulate feeding signals for energy metabolism. Disruption of central 5-HT signaling via 5-HT2C receptors (5-HT2CRs) induces leptin-independent hyperphagia in mice, leading to late-onset obesity, insulin resistance, and impaired glucose tolerance. 5-HT2CR mutant mice are more responsive than wild-type mice to a high-fat diet, exhibiting earlier-onset obesity and type 2 diabetes. High-fat and high-carbohydrate diets increase plasma 5-HT and fibroblast growth factor-21 (FGF21) levels. Plasma 5-HT and FGF21 levels are increased in rodents and humans with obesity, type 2 diabetes, and non-alcohol fatty liver diseases (NAFLD). The increases in plasma FGF21 and hepatic FGF21 expression precede hyperinsulinemia, insulin resistance, hyperglycemia, and weight gain in mice fed a high-fat diet. Nutritional, pharmacologic, or genetic inhibition of peripheral 5-HT synthesis via tryptophan hydroxylase 1 (Tph1) decreases hepatic FGF21 expression and plasma FGF21 levels in mice. Thus, perturbing central 5-HT signaling via 5-HT2CRs alters feeding behavior. Increased energy intake via a high-fat diet and/or high-carbohydrate diet can upregulate gut-derived 5-HT synthesis via Tph1. Peripheral 5-HT upregulates hepatic FGF21 expression and plasma FGF21 levels, leading to metabolic diseases such as obesity, insulin resistance, type 2 diabetes, and NAFLD. The 5-HT network in the brain–gut–liver axis regulates feeding signals and may be involved in the development and/or prevention of metabolic diseases. |
| first_indexed | 2024-03-09T23:45:25Z |
| format | Article |
| id | doaj.art-0f1fe68291c64bffa3a8f8ac6238100f |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T23:45:25Z |
| publishDate | 2022-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-0f1fe68291c64bffa3a8f8ac6238100f2023-11-23T16:43:12ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-01-01233160010.3390/ijms23031600The Regulatory Role of the Central and Peripheral Serotonin Network on Feeding Signals in Metabolic DiseasesKatsunori Nonogaki0Laboratory of Diabetes and Nutrition, New Industry Creation Hatchery Center, Tohoku University, Sendai 980-8579, JapanCentral and peripheral serotonin (5-hydroxytryptamine, 5-HT) regulate feeding signals for energy metabolism. Disruption of central 5-HT signaling via 5-HT2C receptors (5-HT2CRs) induces leptin-independent hyperphagia in mice, leading to late-onset obesity, insulin resistance, and impaired glucose tolerance. 5-HT2CR mutant mice are more responsive than wild-type mice to a high-fat diet, exhibiting earlier-onset obesity and type 2 diabetes. High-fat and high-carbohydrate diets increase plasma 5-HT and fibroblast growth factor-21 (FGF21) levels. Plasma 5-HT and FGF21 levels are increased in rodents and humans with obesity, type 2 diabetes, and non-alcohol fatty liver diseases (NAFLD). The increases in plasma FGF21 and hepatic FGF21 expression precede hyperinsulinemia, insulin resistance, hyperglycemia, and weight gain in mice fed a high-fat diet. Nutritional, pharmacologic, or genetic inhibition of peripheral 5-HT synthesis via tryptophan hydroxylase 1 (Tph1) decreases hepatic FGF21 expression and plasma FGF21 levels in mice. Thus, perturbing central 5-HT signaling via 5-HT2CRs alters feeding behavior. Increased energy intake via a high-fat diet and/or high-carbohydrate diet can upregulate gut-derived 5-HT synthesis via Tph1. Peripheral 5-HT upregulates hepatic FGF21 expression and plasma FGF21 levels, leading to metabolic diseases such as obesity, insulin resistance, type 2 diabetes, and NAFLD. The 5-HT network in the brain–gut–liver axis regulates feeding signals and may be involved in the development and/or prevention of metabolic diseases.https://www.mdpi.com/1422-0067/23/3/1600serotoninfeeding signalsenergy metabolism5-HT2CRsFGF21obesity |
| spellingShingle | Katsunori Nonogaki The Regulatory Role of the Central and Peripheral Serotonin Network on Feeding Signals in Metabolic Diseases International Journal of Molecular Sciences serotonin feeding signals energy metabolism 5-HT2CRs FGF21 obesity |
| title | The Regulatory Role of the Central and Peripheral Serotonin Network on Feeding Signals in Metabolic Diseases |
| title_full | The Regulatory Role of the Central and Peripheral Serotonin Network on Feeding Signals in Metabolic Diseases |
| title_fullStr | The Regulatory Role of the Central and Peripheral Serotonin Network on Feeding Signals in Metabolic Diseases |
| title_full_unstemmed | The Regulatory Role of the Central and Peripheral Serotonin Network on Feeding Signals in Metabolic Diseases |
| title_short | The Regulatory Role of the Central and Peripheral Serotonin Network on Feeding Signals in Metabolic Diseases |
| title_sort | regulatory role of the central and peripheral serotonin network on feeding signals in metabolic diseases |
| topic | serotonin feeding signals energy metabolism 5-HT2CRs FGF21 obesity |
| url | https://www.mdpi.com/1422-0067/23/3/1600 |
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