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PLoS One. 2013;8(7):e65505.

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

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제1저자 최형진 · 교신저자 신찬수

소속 (1)
  1. Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.

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.

Figures

Figure 1
Figure 1 Effect of chronic ICV ghrelin infusion on (A) body weight and (B) food intake. Three groups of rats (4–6 per group) were infused for 21 days with saline or ghrelin (1.5 μg/day). Rats infused with ghrelin were ad lib-fed or pair-fed (to saline-infused rats). * P<0.05 vs. control; † P<0.05 vs. paired-fed. Data are presented as the mean±SEM.
Figure 2
Figure 2 Effect of chronic ICV ghrelin infusion on the tibia trabecular bone phenotype. (A) Trabecular bone volume expressed as percentage of total tissue volume (BV/TV). (B) Trabecular thickness (Tb.Th). (C) Trabecular number (Tb.N). (D) Trabecular separation (Tb.Sp). (E) Trabecular pattern factor (Tb.Pf). (F) Structure model index (SMI); a lower SMI indicate plate-like structure, whereas a higher SMI indicate sphere-like structure. (G) Trabecular volumetric BMD. (H) Representative microCT images of the proximal tibia. Three groups of rats (4–6 per group) were infused for 21 days with saline or ghrelin (1.5 μg/day). Rats infused with ghrelin were ad lib-fed or pair-fed (to saline-infused rats). * P<0.05; † P<0.1. Data are presented as the mean ± SEM.
Figure 3
Figure 3 Effect of chronic ICV ghrelin infusion on the dynamic parameters of histomorphometric analyses. (A–B) Dynamic histomorphometric analyses of lumbar spine, including mineral apposition rate (MAR) and bone formation rate (BFR). (C) Representative fluorescent images obtained from lumbar spine after calcein double labeling (100× magnification). Three groups of rats (4–6 per group) were infused for 21 days with saline or ghrelin (1.5 μg/day). Rats infused with ghrelin were ad lib-fed or pair-fed (to saline-infused rats). * P<0.05; Data are presented as the mean ± SEM.
Figure 4
Figure 4 Effect of chronic ICV ghrelin infusion on serum ghrelin (A) and serum leptin (B). Three groups of rats (4–6 per group) were infused for 21 days with saline or ghrelin (1.5 μg/day). Rats infused with ghrelin were ad lib-fed or pair-fed (to saline-infused rats). * P<0.05. Data are presented as the mean ± SEM.

그림 출처: PubMed Central 공개 논문 (PMC3699588)

Conflict of interest statement

Competing Interests:The authors have declared that no competing interests exist.

그 밖의 정보
출판 형태
Journal Article, Research Support, Non-U.S. Gov't
저널
PloS one · eISSN 1932-6203
전자 출판
2013-07-02
MeSH
Animals · Appetite / physiology · Bone Density / drug effects · Bone and Bones / anatomy & histology / diagnostic imaging / drug effects / metabolism · Drug Administration Schedule · Eating / drug effects · Ghrelin / administration & dosage / blood · Injections, Intraventricular · Leptin / blood · Male · Radiography · Rats · Rats, Sprague-Dawley · Weight Gain / drug effects
Substances
Ghrelin · Leptin
참고문헌
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