Mitochondria-derived peptide SHLP2 regulates energy homeostasis through the activation of hypothalamic neurons
Abstract Small humanin-like peptide 2 (SHLP2) is a mitochondrial-derived peptide implicated in several biological processes such as aging and oxidative stress. However, its functional role in the regulation of energy homeostasis remains unclear, and its corresponding receptor is not identified. Here...
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| Format: | Article |
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Nature Portfolio
2023-07-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-023-40082-7 |
| _version_ | 1797557885681532928 |
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| author | Seul Ki Kim Le Trung Tran Cherl NamKoong Hyung Jin Choi Hye Jin Chun Yong-ho Lee MyungHyun Cheon ChiHye Chung Junmo Hwang Hyun-Ho Lim Dong Min Shin Yun-Hee Choi Ki Woo Kim |
| author_facet | Seul Ki Kim Le Trung Tran Cherl NamKoong Hyung Jin Choi Hye Jin Chun Yong-ho Lee MyungHyun Cheon ChiHye Chung Junmo Hwang Hyun-Ho Lim Dong Min Shin Yun-Hee Choi Ki Woo Kim |
| author_sort | Seul Ki Kim |
| collection | DOAJ |
| description | Abstract Small humanin-like peptide 2 (SHLP2) is a mitochondrial-derived peptide implicated in several biological processes such as aging and oxidative stress. However, its functional role in the regulation of energy homeostasis remains unclear, and its corresponding receptor is not identified. Hereby, we demonstrate that both systemic and intracerebroventricular (ICV) administrations of SHLP2 protected the male mice from high-fat diet (HFD)-induced obesity and improved insulin sensitivity. In addition, the activation of pro-opiomelanocortin (POMC) neurons by SHLP2 in the arcuate nucleus of the hypothalamus (ARC) is involved in the suppression of food intake and the promotion of thermogenesis. Through high-throughput structural complementation screening, we discovered that SHLP2 binds to and activates chemokine receptor 7 (CXCR7). Taken together, our study not only reveals the therapeutic potential of SHLP2 in metabolic disorders but also provides important mechanistic insights into how it exerts its effects on energy homeostasis. |
| first_indexed | 2024-03-10T17:22:39Z |
| format | Article |
| id | doaj.art-9d47fe4c749a4b879e4405811fb86035 |
| institution | Directory Open Access Journal |
| issn | 2041-1723 |
| language | English |
| last_indexed | 2024-03-10T17:22:39Z |
| publishDate | 2023-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj.art-9d47fe4c749a4b879e4405811fb860352023-11-20T10:18:08ZengNature PortfolioNature Communications2041-17232023-07-0114111410.1038/s41467-023-40082-7Mitochondria-derived peptide SHLP2 regulates energy homeostasis through the activation of hypothalamic neuronsSeul Ki Kim0Le Trung Tran1Cherl NamKoong2Hyung Jin Choi3Hye Jin Chun4Yong-ho Lee5MyungHyun Cheon6ChiHye Chung7Junmo Hwang8Hyun-Ho Lim9Dong Min Shin10Yun-Hee Choi11Ki Woo Kim12Division of Physiology, Department of Oral Biology, Yonsei University College of DentistryDivision of Physiology, Department of Oral Biology, Yonsei University College of DentistryNeuroscience Research Institute, Seoul National University College of MedicineNeuroscience Research Institute, Seoul National University College of MedicineDepartment of Internal Medicine, Yonsei University College of MedicineDepartment of Internal Medicine, Yonsei University College of MedicineDepartment of Biological Sciences, Konkuk UniversityDepartment of Biological Sciences, Konkuk UniversityNeurovascular Unit Research Group, Korea Brain Research Institute (KBRI)Neurovascular Unit Research Group, Korea Brain Research Institute (KBRI)Division of Physiology, Department of Oral Biology, Yonsei University College of DentistryDivision of Physiology, Department of Oral Biology, Yonsei University College of DentistryDivision of Physiology, Department of Oral Biology, Yonsei University College of DentistryAbstract Small humanin-like peptide 2 (SHLP2) is a mitochondrial-derived peptide implicated in several biological processes such as aging and oxidative stress. However, its functional role in the regulation of energy homeostasis remains unclear, and its corresponding receptor is not identified. Hereby, we demonstrate that both systemic and intracerebroventricular (ICV) administrations of SHLP2 protected the male mice from high-fat diet (HFD)-induced obesity and improved insulin sensitivity. In addition, the activation of pro-opiomelanocortin (POMC) neurons by SHLP2 in the arcuate nucleus of the hypothalamus (ARC) is involved in the suppression of food intake and the promotion of thermogenesis. Through high-throughput structural complementation screening, we discovered that SHLP2 binds to and activates chemokine receptor 7 (CXCR7). Taken together, our study not only reveals the therapeutic potential of SHLP2 in metabolic disorders but also provides important mechanistic insights into how it exerts its effects on energy homeostasis.https://doi.org/10.1038/s41467-023-40082-7 |
| spellingShingle | Seul Ki Kim Le Trung Tran Cherl NamKoong Hyung Jin Choi Hye Jin Chun Yong-ho Lee MyungHyun Cheon ChiHye Chung Junmo Hwang Hyun-Ho Lim Dong Min Shin Yun-Hee Choi Ki Woo Kim Mitochondria-derived peptide SHLP2 regulates energy homeostasis through the activation of hypothalamic neurons Nature Communications |
| title | Mitochondria-derived peptide SHLP2 regulates energy homeostasis through the activation of hypothalamic neurons |
| title_full | Mitochondria-derived peptide SHLP2 regulates energy homeostasis through the activation of hypothalamic neurons |
| title_fullStr | Mitochondria-derived peptide SHLP2 regulates energy homeostasis through the activation of hypothalamic neurons |
| title_full_unstemmed | Mitochondria-derived peptide SHLP2 regulates energy homeostasis through the activation of hypothalamic neurons |
| title_short | Mitochondria-derived peptide SHLP2 regulates energy homeostasis through the activation of hypothalamic neurons |
| title_sort | mitochondria derived peptide shlp2 regulates energy homeostasis through the activation of hypothalamic neurons |
| url | https://doi.org/10.1038/s41467-023-40082-7 |
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