eLife (Nov 2020)
Lipocalin-2 is an anorexigenic signal in primates
- 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
Affiliations
- Peristera-Ioanna Petropoulou
- ORCiD
- Department of Physiology and Cellular Biophysics, Columbia University Medical Center, New York, United States
- Ioanna Mosialou
- ORCiD
- Department of Physiology and Cellular Biophysics, Columbia University Medical Center, New York, United States
- Steven Shikhel
- Department of Physiology and Cellular Biophysics, Columbia University Medical Center, New York, United States
- Lihong Hao
- ORCiD
- Department of Nutritional Sciences, Rutgers University, New Brunswick, United States
- Konstantinos Panitsas
- Department of Physiology and Cellular Biophysics, Columbia University Medical Center, New York, United States
- Brygida Bisikirska
- Department of Physiology and Cellular Biophysics, Columbia University Medical Center, New York, United States
- Na Luo
- Department of Physiology and Cellular Biophysics, Columbia University Medical Center, New York, United States
- Fabiana Bahna
- Department of Biochemistry and Molecular Biophysics, Columbia University, New York, United States
- Jongho Kim
- Department of Radiology, Columbia University Medical Center, New York, United States
- Patrick Carberry
- Department of Radiology, Columbia University Medical Center, New York, United States
- Francesca Zanderigo
- Department of Psychiatry, Columbia University Medical Center, New York, United States; Molecular Imaging and Neuropathology Area, New York State Psychiatric Institute, New York, United States
- Norman Simpson
- Department of Psychiatry, Columbia University Medical Center, New York, United States
- Mihran Bakalian
- ORCiD
- Department of Psychiatry, Columbia University Medical Center, New York, United States
- Suham Kassir
- Department of Psychiatry, Columbia University Medical Center, New York, United States; Molecular Imaging and Neuropathology Area, New York State Psychiatric Institute, New York, United States
- Lawrence Shapiro
- ORCiD
- Department of Biochemistry and Molecular Biophysics, Columbia University, New York, United States
- Mark D Underwood
- Department of Psychiatry, Columbia University Medical Center, New York, United States; Molecular Imaging and Neuropathology Area, New York State Psychiatric Institute, New York, United States
- Christina M May
- Department of Pathology, Section on Comparative Medicine, Wake Forest School of Medicine, Winston-Salem, United States
- Kiran Kumar Soligapuram Sai
- Department of Radiology, Wake Forest School of Medicine, Winston-Salem, United States
- Matthew J Jorgensen
- ORCiD
- Department of Pathology, Section on Comparative Medicine, Wake Forest School of Medicine, Winston-Salem, United States
- Cyrille B Confavreux
- INSERM UMR1033-Université de Lyon-Hospices Civils de Lyon, Lyon, France
- Sue Shapses
- Department of Nutritional Sciences, Rutgers University, New Brunswick, United States; Department of Medicine, Rutgers - RWJ Medical School, Rutgers University, New Brunswick, United States
- Blandine Laferrère
- New 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 States
- Akiva Mintz
- Department of Radiology, Columbia University Medical Center, New York, United States
- J John Mann
- Department 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 States
- Mishaela Rubin
- New York Obesity Nutrition Research Center, Columbia University, New York, United States
- Stavroula Kousteni
- ORCiD
- Department of Physiology and Cellular Biophysics, Columbia University Medical Center, New York, United States
- DOI
- https://doi.org/10.7554/eLife.58949
- Journal volume & issue
-
Vol. 9
Abstract
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.
Keywords
