International Journal of Medical Sciences

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22 April 2019

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Int J Med Sci 2018; 15(10):969-977. doi:10.7150/ijms.24373

Research Paper

RANKL Reduces Body Weight and Food Intake via the Modulation of Hypothalamic NPY/CART Expression

Ping Zhu1*, Zhihui Zhang1*, Xufeng Huang2, Shiyu Liang1, Neeta Khandekar3, Zhiyuan Song1✉, Shu Lin1,2✉

1. Department of Cardiology, Southwest Hospital, Third Military Medical University (Army Medical University), China
2. School of Medicine, University of Wollongong and Illawarra Health and Medical Research Institute, NSW 2522, Australia
3. Neurological Diseases Division, Research Program, Garvan Institute of Medical Research, 384 Victoria Street, Darlinghurst, Sydney, NSW 2010, Australia
* These authors contributed equally to this work.


The receptor activator of nuclear factor-κB ligand (RANKL) modulates energy metabolism. However, how RANKL regulates energy homeostasis is still not clear. This study aims to investigate the central mechanisms by which central administration of RANKL inhibits food intake and causes weight loss in mice. We carried out a systematic and in-depth analysis of the neuronal pathways by which RANKL mediates catabolic effects. After intracerebroventricle (i.c.v.) injection of RANKL, the expression of neuropeptide Y (NPY) mRNA in the Arc was significantly decreased, while the CART mRNA expression dramatically increased in the Arc and DMH. However, the agouti-related protein (AgRP) and pro-opiomelanocortin (POMC) mRNA had no significant changes compared with control groups. Together, the results suggest that central administration of RANKL reduces food intake and causes weight loss via modulating the hypothalamic NPY/CART pathways.

Keywords: Receptor activator of NF-κB ligand, Food intake, Cocaine- and amphetamine-regulated transcript, Neuropeptide Y, Hypothalamus

This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) license ( See for full terms and conditions.
How to cite this article:
Zhu P, Zhang Z, Huang X, Liang S, Khandekar N, Song Z, Lin S. RANKL Reduces Body Weight and Food Intake via the Modulation of Hypothalamic NPY/CART Expression. Int J Med Sci 2018; 15(10):969-977. doi:10.7150/ijms.24373. Available from