Involvement of POMC neurons in LEAP2 regulation of food intake and body weight
Liver-expressed antimicrobial peptide 2 (LEAP2) is a newly discovered antagonist of the growth hormone secretagogue receptor (GHSR) and is considered the first endogenous peptide that can antagonize the metabolic actions of ghrelin. The effects of ghrelin administration on feeding behavior, body wei...
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| Format: | Article |
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Frontiers Media S.A.
2022-10-01
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| Series: | Frontiers in Endocrinology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fendo.2022.932761/full |
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| author | Guangpin Chu Hualing Peng Nana Yu Yuejin Zhang Xueling Lin Yisheng Lu Yisheng Lu Yisheng Lu |
| author_facet | Guangpin Chu Hualing Peng Nana Yu Yuejin Zhang Xueling Lin Yisheng Lu Yisheng Lu Yisheng Lu |
| author_sort | Guangpin Chu |
| collection | DOAJ |
| description | Liver-expressed antimicrobial peptide 2 (LEAP2) is a newly discovered antagonist of the growth hormone secretagogue receptor (GHSR) and is considered the first endogenous peptide that can antagonize the metabolic actions of ghrelin. The effects of ghrelin administration on feeding behavior, body weight, and energy metabolism involve the activation of orexigenic neurons in the arcuate nucleus (ARC) of the hypothalamus. It is unclear, however, if LEAP2 applied directly to the ARC of the hypothalamus affects these metabolic processes. Here, we show that overexpression of LEAP2 in the ARC through adeno-associated virus (AAV) reduced food intake and body weight in wild-type (WT) mice fed chow and a high-fat diet (HFD) and improved metabolic disorders. LEAP2 overexpression in the ARC overrides both central and peripheral ghrelin action on a chow diet. Interestingly, this AAV-LEAP2 treatment increased proopiomelanocortin (POMC) expression while agouti-related peptide (AGRP)/neuropeptide Y (NPY) and GHSR levels remained unchanged in the hypothalamus. Additionally, intracerebroventricular (i.c.v.) administration of LEAP2 decreased food intake, increased POMC neuronal activity, and repeated LEAP2 administration to mice induced body weight loss. Using chemogenetic manipulations, we found that inhibition of POMC neurons abolished the anorexigenic effect of LEAP2. These results demonstrate that central delivery of LEAP2 leads to appetite-suppressing and body weight reduction, which might require activation of POMC neurons in the ARC. |
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| format | Article |
| id | doaj.art-148fa947d81f4e1bab43fcbb52ad92e1 |
| institution | Directory Open Access Journal |
| issn | 1664-2392 |
| language | English |
| last_indexed | 2024-04-12T18:00:00Z |
| publishDate | 2022-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Endocrinology |
| spelling | doaj.art-148fa947d81f4e1bab43fcbb52ad92e12022-12-22T03:22:11ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922022-10-011310.3389/fendo.2022.932761932761Involvement of POMC neurons in LEAP2 regulation of food intake and body weightGuangpin Chu0Hualing Peng1Nana Yu2Yuejin Zhang3Xueling Lin4Yisheng Lu5Yisheng Lu6Yisheng Lu7Department of Physiology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Physiology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Physiology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Physiology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Physiology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Physiology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaInstitute of Brain Research, Collaborative Innovation Center for Brain Science, Huazhong University of Science and Technology, Wuhan, ChinaHubei Key Laboratory of Drug Target Research and Pharmacodynamic Evaluation, Huazhong University of Science and Technology, Wuhan, ChinaLiver-expressed antimicrobial peptide 2 (LEAP2) is a newly discovered antagonist of the growth hormone secretagogue receptor (GHSR) and is considered the first endogenous peptide that can antagonize the metabolic actions of ghrelin. The effects of ghrelin administration on feeding behavior, body weight, and energy metabolism involve the activation of orexigenic neurons in the arcuate nucleus (ARC) of the hypothalamus. It is unclear, however, if LEAP2 applied directly to the ARC of the hypothalamus affects these metabolic processes. Here, we show that overexpression of LEAP2 in the ARC through adeno-associated virus (AAV) reduced food intake and body weight in wild-type (WT) mice fed chow and a high-fat diet (HFD) and improved metabolic disorders. LEAP2 overexpression in the ARC overrides both central and peripheral ghrelin action on a chow diet. Interestingly, this AAV-LEAP2 treatment increased proopiomelanocortin (POMC) expression while agouti-related peptide (AGRP)/neuropeptide Y (NPY) and GHSR levels remained unchanged in the hypothalamus. Additionally, intracerebroventricular (i.c.v.) administration of LEAP2 decreased food intake, increased POMC neuronal activity, and repeated LEAP2 administration to mice induced body weight loss. Using chemogenetic manipulations, we found that inhibition of POMC neurons abolished the anorexigenic effect of LEAP2. These results demonstrate that central delivery of LEAP2 leads to appetite-suppressing and body weight reduction, which might require activation of POMC neurons in the ARC.https://www.frontiersin.org/articles/10.3389/fendo.2022.932761/fullliver-expressed antimicrobial peptide 2 (LEAP2)arcuate nucleus (ARC)food intakeenergy metabolismproopiomelanocortin (POMC) |
| spellingShingle | Guangpin Chu Hualing Peng Nana Yu Yuejin Zhang Xueling Lin Yisheng Lu Yisheng Lu Yisheng Lu Involvement of POMC neurons in LEAP2 regulation of food intake and body weight Frontiers in Endocrinology liver-expressed antimicrobial peptide 2 (LEAP2) arcuate nucleus (ARC) food intake energy metabolism proopiomelanocortin (POMC) |
| title | Involvement of POMC neurons in LEAP2 regulation of food intake and body weight |
| title_full | Involvement of POMC neurons in LEAP2 regulation of food intake and body weight |
| title_fullStr | Involvement of POMC neurons in LEAP2 regulation of food intake and body weight |
| title_full_unstemmed | Involvement of POMC neurons in LEAP2 regulation of food intake and body weight |
| title_short | Involvement of POMC neurons in LEAP2 regulation of food intake and body weight |
| title_sort | involvement of pomc neurons in leap2 regulation of food intake and body weight |
| topic | liver-expressed antimicrobial peptide 2 (LEAP2) arcuate nucleus (ARC) food intake energy metabolism proopiomelanocortin (POMC) |
| url | https://www.frontiersin.org/articles/10.3389/fendo.2022.932761/full |
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