GPSM1 in POMC neurons impairs brown adipose tissue thermogenesis and provokes diet-induced obesity
Objective: G-protein-signaling modulator 1 (GPSM1) has been proved the potential role in brain tissues, however, whether GPSM1 in hypothalamic nuclei, especially in POMC neurons is essential for the proper regulation of whole-body energy balance remains unknown. The aim of our current study was to e...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2024-01-01
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| Series: | Molecular Metabolism |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2212877823001734 |
| _version_ | 1797342266662060032 |
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| author | Mengyang Tang Yi Zhang Rong Zhang Yuemei Zhang Jiangfei Zheng Daixi Wang Xinyu Wang Jing Yan Cheng Hu |
| author_facet | Mengyang Tang Yi Zhang Rong Zhang Yuemei Zhang Jiangfei Zheng Daixi Wang Xinyu Wang Jing Yan Cheng Hu |
| author_sort | Mengyang Tang |
| collection | DOAJ |
| description | Objective: G-protein-signaling modulator 1 (GPSM1) has been proved the potential role in brain tissues, however, whether GPSM1 in hypothalamic nuclei, especially in POMC neurons is essential for the proper regulation of whole-body energy balance remains unknown. The aim of our current study was to explore the role of GPSM1 in POMC neurons in metabolic homeostasis. Methods: We generated POMC neuron specific GPSM1 deficiency mice and subjected them to a High Fat Diet to monitor metabolic phenotypes in vivo. By using various molecular, biochemical, immunofluorescent, immunohistochemical analyses, and cell culture studies to reveal the pathophysiological role of GPSM1 in POMC neurons and elucidate the underlying mechanisms of GPSM1 regulating POMC neurons activity. Results: We demonstrated that mice lacking GPSM1 in POMC neurons were protected against diet-induced obesity, glucose dysregulation, insulin resistance, and hepatic steatosis. Mechanistically, GPSM1 deficiency in POMC neurons induced enhanced autophagy and improved leptin sensitivity through PI3K/AKT/mTOR signaling, thereby increasing POMC expression and α-MSH production, and concurrently enhancing sympathetic innervation and activity, thus resulting in decreased food intake and increased brown adipose tissue thermogenesis. Conclusions: Our findings identify a novel function of GPSM1 expressed in POMC neurons in the regulation of whole-body energy balance and metabolic homeostasis by regulating autophagy and leptin sensitivity, which suggests that GPSM1 in the POMC neurons could be a promising therapeutic target to combat obesity and obesity-related metabolic disorders. |
| first_indexed | 2024-03-08T10:30:49Z |
| format | Article |
| id | doaj.art-d06c803feb644c8ea6c7269eab0bcdcc |
| institution | Directory Open Access Journal |
| issn | 2212-8778 |
| language | English |
| last_indexed | 2024-03-08T10:30:49Z |
| publishDate | 2024-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Molecular Metabolism |
| spelling | doaj.art-d06c803feb644c8ea6c7269eab0bcdcc2024-01-27T06:54:34ZengElsevierMolecular Metabolism2212-87782024-01-0179101839GPSM1 in POMC neurons impairs brown adipose tissue thermogenesis and provokes diet-induced obesityMengyang Tang0Yi Zhang1Rong Zhang2Yuemei Zhang3Jiangfei Zheng4Daixi Wang5Xinyu Wang6Jing Yan7Cheng Hu8The Third School of Clinical Medicine, Southern Medical University, Guangzhou, China; Department of Endocrinology and Metabolism, Fengxian Central Hospital Affiliated to Southern Medical University, Shanghai, ChinaShanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Clinical Center for Diabetes, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaShanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Clinical Center for Diabetes, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaShanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Clinical Center for Diabetes, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaShanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Clinical Center for Diabetes, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaShanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Clinical Center for Diabetes, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaSchool of Life Science and Technology of ShanghaiTech University, Shanghai, ChinaShanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Clinical Center for Diabetes, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China; Corresponding author.The Third School of Clinical Medicine, Southern Medical University, Guangzhou, China; Department of Endocrinology and Metabolism, Fengxian Central Hospital Affiliated to Southern Medical University, Shanghai, China; Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Clinical Center for Diabetes, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China; Corresponding author.The Third School of Clinical Medicine, Southern Medical University, Guangzhou, China.Objective: G-protein-signaling modulator 1 (GPSM1) has been proved the potential role in brain tissues, however, whether GPSM1 in hypothalamic nuclei, especially in POMC neurons is essential for the proper regulation of whole-body energy balance remains unknown. The aim of our current study was to explore the role of GPSM1 in POMC neurons in metabolic homeostasis. Methods: We generated POMC neuron specific GPSM1 deficiency mice and subjected them to a High Fat Diet to monitor metabolic phenotypes in vivo. By using various molecular, biochemical, immunofluorescent, immunohistochemical analyses, and cell culture studies to reveal the pathophysiological role of GPSM1 in POMC neurons and elucidate the underlying mechanisms of GPSM1 regulating POMC neurons activity. Results: We demonstrated that mice lacking GPSM1 in POMC neurons were protected against diet-induced obesity, glucose dysregulation, insulin resistance, and hepatic steatosis. Mechanistically, GPSM1 deficiency in POMC neurons induced enhanced autophagy and improved leptin sensitivity through PI3K/AKT/mTOR signaling, thereby increasing POMC expression and α-MSH production, and concurrently enhancing sympathetic innervation and activity, thus resulting in decreased food intake and increased brown adipose tissue thermogenesis. Conclusions: Our findings identify a novel function of GPSM1 expressed in POMC neurons in the regulation of whole-body energy balance and metabolic homeostasis by regulating autophagy and leptin sensitivity, which suggests that GPSM1 in the POMC neurons could be a promising therapeutic target to combat obesity and obesity-related metabolic disorders.http://www.sciencedirect.com/science/article/pii/S2212877823001734ObesityThermogenesisAutophagyLeptin sensitivityGPSM1 |
| spellingShingle | Mengyang Tang Yi Zhang Rong Zhang Yuemei Zhang Jiangfei Zheng Daixi Wang Xinyu Wang Jing Yan Cheng Hu GPSM1 in POMC neurons impairs brown adipose tissue thermogenesis and provokes diet-induced obesity Molecular Metabolism Obesity Thermogenesis Autophagy Leptin sensitivity GPSM1 |
| title | GPSM1 in POMC neurons impairs brown adipose tissue thermogenesis and provokes diet-induced obesity |
| title_full | GPSM1 in POMC neurons impairs brown adipose tissue thermogenesis and provokes diet-induced obesity |
| title_fullStr | GPSM1 in POMC neurons impairs brown adipose tissue thermogenesis and provokes diet-induced obesity |
| title_full_unstemmed | GPSM1 in POMC neurons impairs brown adipose tissue thermogenesis and provokes diet-induced obesity |
| title_short | GPSM1 in POMC neurons impairs brown adipose tissue thermogenesis and provokes diet-induced obesity |
| title_sort | gpsm1 in pomc neurons impairs brown adipose tissue thermogenesis and provokes diet induced obesity |
| topic | Obesity Thermogenesis Autophagy Leptin sensitivity GPSM1 |
| url | http://www.sciencedirect.com/science/article/pii/S2212877823001734 |
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