Lipocalin-2 is an anorexigenic signal in primates
In the mouse, the osteoblast-derived hormone Lipocalin-2 (LCN2) suppresses food intake and acts as a satiety signal. We show here that meal challenges increase serum LCN2 levels in persons with normal or overweight, but not in individuals with obesity. Postprandial LCN2 serum levels correlate invers...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
eLife Sciences Publications Ltd
2020-11-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/58949 |
| _version_ | 1811181505749188608 |
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| author | Peristera-Ioanna Petropoulou Ioanna Mosialou Steven Shikhel Lihong Hao Konstantinos Panitsas Brygida Bisikirska Na Luo Fabiana Bahna Jongho Kim Patrick Carberry Francesca Zanderigo Norman Simpson Mihran Bakalian Suham Kassir Lawrence Shapiro Mark D Underwood Christina M May Kiran Kumar Soligapuram Sai Matthew J Jorgensen Cyrille B Confavreux Sue Shapses Blandine Laferrère Akiva Mintz J John Mann Mishaela Rubin Stavroula Kousteni |
| author_facet | Peristera-Ioanna Petropoulou Ioanna Mosialou Steven Shikhel Lihong Hao Konstantinos Panitsas Brygida Bisikirska Na Luo Fabiana Bahna Jongho Kim Patrick Carberry Francesca Zanderigo Norman Simpson Mihran Bakalian Suham Kassir Lawrence Shapiro Mark D Underwood Christina M May Kiran Kumar Soligapuram Sai Matthew J Jorgensen Cyrille B Confavreux Sue Shapses Blandine Laferrère Akiva Mintz J John Mann Mishaela Rubin Stavroula Kousteni |
| author_sort | Peristera-Ioanna Petropoulou |
| collection | DOAJ |
| description | In the mouse, the osteoblast-derived hormone Lipocalin-2 (LCN2) suppresses food intake and acts as a satiety signal. We show here that meal challenges increase serum LCN2 levels in persons with normal or overweight, but not in individuals with obesity. Postprandial LCN2 serum levels correlate inversely with hunger sensation in challenged subjects. We further show through brain PET scans of monkeys injected with radiolabeled recombinant human LCN2 (rh-LCN2) and autoradiography in baboon, macaque, and human brain sections, that LCN2 crosses the blood-brain barrier and localizes to the hypothalamus in primates. In addition, daily treatment of lean monkeys with rh-LCN2 decreases food intake by 21%, without overt side effects. These studies demonstrate the biology of LCN2 as a satiety factor and indicator and anorexigenic signal in primates. Failure to stimulate postprandial LCN2 in individuals with obesity may contribute to metabolic dysregulation, suggesting that LCN2 may be a novel target for obesity treatment. |
| first_indexed | 2024-04-11T09:18:24Z |
| format | Article |
| id | doaj.art-b2734d3dbbc54f4eb86187281ddbff78 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-11T09:18:24Z |
| publishDate | 2020-11-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-b2734d3dbbc54f4eb86187281ddbff782022-12-22T04:32:16ZengeLife Sciences Publications LtdeLife2050-084X2020-11-01910.7554/eLife.58949Lipocalin-2 is an anorexigenic signal in primatesPeristera-Ioanna Petropoulou0https://orcid.org/0000-0001-7844-3010Ioanna Mosialou1https://orcid.org/0000-0003-0339-3316Steven Shikhel2Lihong Hao3https://orcid.org/0000-0001-7795-6981Konstantinos Panitsas4Brygida Bisikirska5Na Luo6Fabiana Bahna7Jongho Kim8Patrick Carberry9Francesca Zanderigo10Norman Simpson11Mihran Bakalian12https://orcid.org/0000-0002-1935-5982Suham Kassir13Lawrence Shapiro14https://orcid.org/0000-0001-9943-8819Mark D Underwood15Christina M May16Kiran Kumar Soligapuram Sai17Matthew J Jorgensen18https://orcid.org/0000-0002-0977-6425Cyrille B Confavreux19Sue Shapses20Blandine Laferrère21Akiva Mintz22J John Mann23Mishaela Rubin24Stavroula Kousteni25https://orcid.org/0000-0001-5163-3551Department of Physiology and Cellular Biophysics, Columbia University Medical Center, New York, United StatesDepartment of Physiology and Cellular Biophysics, Columbia University Medical Center, New York, United StatesDepartment of Physiology and Cellular Biophysics, Columbia University Medical Center, New York, United StatesDepartment of Nutritional Sciences, Rutgers University, New Brunswick, United StatesDepartment of Physiology and Cellular Biophysics, Columbia University Medical Center, New York, United StatesDepartment of Physiology and Cellular Biophysics, Columbia University Medical Center, New York, United StatesDepartment of Physiology and Cellular Biophysics, Columbia University Medical Center, New York, United StatesDepartment of Biochemistry and Molecular Biophysics, Columbia University, New York, United StatesDepartment of Radiology, Columbia University Medical Center, New York, United StatesDepartment of Radiology, Columbia University Medical Center, New York, United StatesDepartment of Psychiatry, Columbia University Medical Center, New York, United States; Molecular Imaging and Neuropathology Area, New York State Psychiatric Institute, New York, United StatesDepartment of Psychiatry, Columbia University Medical Center, New York, United StatesDepartment of Psychiatry, Columbia University Medical Center, New York, United StatesDepartment of Psychiatry, Columbia University Medical Center, New York, United States; Molecular Imaging and Neuropathology Area, New York State Psychiatric Institute, New York, United StatesDepartment of Biochemistry and Molecular Biophysics, Columbia University, New York, United StatesDepartment of Psychiatry, Columbia University Medical Center, New York, United States; Molecular Imaging and Neuropathology Area, New York State Psychiatric Institute, New York, United StatesDepartment of Pathology, Section on Comparative Medicine, Wake Forest School of Medicine, Winston-Salem, United StatesDepartment of Radiology, Wake Forest School of Medicine, Winston-Salem, United StatesDepartment of Pathology, Section on Comparative Medicine, Wake Forest School of Medicine, Winston-Salem, United StatesINSERM UMR1033-Université de Lyon-Hospices Civils de Lyon, Lyon, FranceDepartment of Nutritional Sciences, Rutgers University, New Brunswick, United States; Department of Medicine, Rutgers - RWJ Medical School, Rutgers University, New Brunswick, United StatesNew York Obesity Nutrition Research Center, Columbia University, New York, United States; Department of Medicine, Division of Endocrinology, Columbia University Irving Medical Center, New York, United StatesDepartment of Radiology, Columbia University Medical Center, New York, United StatesDepartment of Radiology, Columbia University Medical Center, New York, United States; Department of Psychiatry, Columbia University Medical Center, New York, United States; Molecular Imaging and Neuropathology Area, New York State Psychiatric Institute, New York, United StatesNew York Obesity Nutrition Research Center, Columbia University, New York, United StatesDepartment of Physiology and Cellular Biophysics, Columbia University Medical Center, New York, United StatesIn the mouse, the osteoblast-derived hormone Lipocalin-2 (LCN2) suppresses food intake and acts as a satiety signal. We show here that meal challenges increase serum LCN2 levels in persons with normal or overweight, but not in individuals with obesity. Postprandial LCN2 serum levels correlate inversely with hunger sensation in challenged subjects. We further show through brain PET scans of monkeys injected with radiolabeled recombinant human LCN2 (rh-LCN2) and autoradiography in baboon, macaque, and human brain sections, that LCN2 crosses the blood-brain barrier and localizes to the hypothalamus in primates. In addition, daily treatment of lean monkeys with rh-LCN2 decreases food intake by 21%, without overt side effects. These studies demonstrate the biology of LCN2 as a satiety factor and indicator and anorexigenic signal in primates. Failure to stimulate postprandial LCN2 in individuals with obesity may contribute to metabolic dysregulation, suggesting that LCN2 may be a novel target for obesity treatment.https://elifesciences.org/articles/58949LCN2postprandialhungerobesityanorexigenicprimates |
| spellingShingle | Peristera-Ioanna Petropoulou Ioanna Mosialou Steven Shikhel Lihong Hao Konstantinos Panitsas Brygida Bisikirska Na Luo Fabiana Bahna Jongho Kim Patrick Carberry Francesca Zanderigo Norman Simpson Mihran Bakalian Suham Kassir Lawrence Shapiro Mark D Underwood Christina M May Kiran Kumar Soligapuram Sai Matthew J Jorgensen Cyrille B Confavreux Sue Shapses Blandine Laferrère Akiva Mintz J John Mann Mishaela Rubin Stavroula Kousteni Lipocalin-2 is an anorexigenic signal in primates eLife LCN2 postprandial hunger obesity anorexigenic primates |
| title | Lipocalin-2 is an anorexigenic signal in primates |
| title_full | Lipocalin-2 is an anorexigenic signal in primates |
| title_fullStr | Lipocalin-2 is an anorexigenic signal in primates |
| title_full_unstemmed | Lipocalin-2 is an anorexigenic signal in primates |
| title_short | Lipocalin-2 is an anorexigenic signal in primates |
| title_sort | lipocalin 2 is an anorexigenic signal in primates |
| topic | LCN2 postprandial hunger obesity anorexigenic primates |
| url | https://elifesciences.org/articles/58949 |
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