Chronic central administration of Ghrelin increases bone mass through a mechanism independent of appetite regulation

PLoS One. 2013 Jul 2;8(7):e65505. doi: 10.1371/journal.pone.0065505. Print 2013.

Abstract

Leptin plays a critical role in the central regulation of bone mass. Ghrelin counteracts leptin. In this study, we investigated the effect of chronic intracerebroventricular administration of ghrelin on bone mass in Sprague-Dawley rats (1.5 μg/day for 21 days). Rats were divided into control, ghrelin ad libitum-fed (ghrelin ad lib-fed), and ghrelin pair-fed groups. Ghrelin intracerebroventricular infusion significantly increased body weight in ghrelin ad lib-fed rats but not in ghrelin pair-fed rats, as compared with control rats. Chronic intracerebroventricular ghrelin infusion significantly increased bone mass in the ghrelin pair-fed group compared with control as indicated by increased bone volume percentage, trabecular thickness, trabecular number and volumetric bone mineral density in tibia trabecular bone. There was no significant difference in trabecular bone mass between the control group and the ghrelin ad-lib fed group. Chronic intracerebroventricular ghrelin infusion significantly increased the mineral apposition rate in the ghrelin pair-fed group as compared with control. In conclusion, chronic central administration of ghrelin increases bone mass through a mechanism that is independent of body weight, suggesting that ghrelin may have a bone anabolic effect through the central nervous system.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Appetite / physiology
  • Bone Density / drug effects*
  • Bone and Bones / anatomy & histology
  • Bone and Bones / diagnostic imaging
  • Bone and Bones / drug effects*
  • Bone and Bones / metabolism
  • Drug Administration Schedule
  • Eating / drug effects
  • Ghrelin / administration & dosage*
  • Ghrelin / blood
  • Injections, Intraventricular
  • Leptin / blood
  • Male
  • Radiography
  • Rats
  • Rats, Sprague-Dawley
  • Weight Gain / drug effects*

Substances

  • Ghrelin
  • Leptin

Grants and funding

This study was supported by a grant of the Korea Health technology Research & Development Project, Ministry of Health & Welfare, Republic of Korea (A110566). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.