Lipocalin-2 is an anorexigenic signal in primates

eLife

Mishaela Rubin¹  Matthew J Jorgensen²  Mark D Underwood²  Norman Simpson²  Christina M May³  Fabiana Bahna³  J John Mann⁴  Lihong Hao⁴  Cyrille B Confavreux⁵  Blandine Laferrère⁵  Konstantinos Panitsas⁶  Peristera-Ioanna Petropoulou⁶  Steven Shikhel⁶  Ioanna Mosialou⁶  Na Luo⁶  Brygida Bisikirska⁶  Kiran Kumar Soligapuram Sai⁷  Lawrence Shapiro⁷  Francesca Zanderigo⁷  Mihran Bakalian⁷  Suham Kassir⁷  Patrick Carberry⁸  Jongho Kim⁸  Sue Shapses⁹  Akiva Mintz^1,10  Stavroula Kousteni^1,11 

[1] Department of Medicine, Rutgers - RWJ Medical School, Rutgers University, New Brunswick, United States;Molecular Imaging and Neuropathology Area, New York State Psychiatric Institute, New York, United States;Department of Biochemistry and Molecular Biophysics, Columbia University, New York, United States;Department of Nutritional Sciences, Rutgers University, New Brunswick, United States;Department of Pathology, Section on Comparative Medicine, Wake Forest School of Medicine, Winston-Salem, United States;Department of Physiology and Cellular Biophysics, Columbia University Medical Center, New York, United States;Department of Psychiatry, Columbia University Medical Center, New York, United States;Department of Radiology, Columbia University Medical Center, New York, United States;Department of Radiology, Wake Forest School of Medicine, Winston-Salem, United States;INSERM UMR1033-Université de Lyon-Hospices Civils de Lyon, Lyon, France;New York Obesity Nutrition Research Center, Columbia University, New York, United States;

关键词: LCN2;    postprandial;    hunger;    obesity;    anorexigenic;    primates;   

DOI  :  10.7554/eLife.58949

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown