Central (ICV) leptin injection increases bone formation, bone mineral density, muscle mass, serum IGF-1, and the expression of osteogenic genes in leptin-deficient ob/ob mice

Shoshana M. Bartell, Srujana Rayalam, Suresh Ambati, Dhanunjaya R. Gaddam, Diane L. Hartzell, Mark W Hamrick, Jin-Xiong She, Mary Anne Della-Fera, Clifton A. Baile

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Abstract

Both central and peripheral leptin administrations reduce body weight, food intake, and adiposity in ob/ob mice. In this study we compared effects of intracerebroventricular (ICV) and subcutaneous (SC) administration of leptin on bone metabolism in the appendicular and axial skeleton and adipose tissue gene expression and determined the effects of ICV leptin on bone marrow gene expression in ob/ob mice. In experiment 1, leptin (1.5 or 0.38μg/d) or control was continuously injected ICV for 12 days. Gene expression analysis of femoral bone marrow stromal cells showed that expression of genes associated with osteogenesis was increased after ICV injection, whereas those associated with osteoclastogenesis, adipogenesis, and adipocyte lipid storage were decreased. In experiment 2, leptin was injected continuously ICV (0.0 or 1.5μg/d) or SC (0.0 or 10μg/d) for 12 days. In both experiments, regardless of mode of administration, leptin decreased body weight, food intake, and body fat and increased muscle mass, bone mineral density, bone mineral content, bone area, marrow adipocyte number, and mineral apposition rate. Serum insulin was decreased, whereas serum osteocalcin, insulin-like growth factor 1, osteoprotegerin, pyridinoline, and receptor activator of nuclear factor κB ligand concentrations were increased. In experiment 2, expression of genes in adipose tissue associated with apoptosis, lipid mobilization, insulin sensitivity, and thermogenesis was increased, whereas expression of genes associated with cell differentiation and maturation was decreased regardless of mode of administration. Thus ICV injection of leptin promotes expression of pro-osteogenic factors in bone marrow, leading to enhanced bone formation in ob/ob mice.

Original languageEnglish (US)
Pages (from-to)1710-1720
Number of pages11
JournalJournal of Bone and Mineral Research
Volume26
Issue number8
DOIs
StatePublished - Aug 1 2011

Fingerprint

Leptin
Insulin-Like Growth Factor I
Osteogenesis
Bone Density
Gene Expression
Bone and Bones
Muscles
Injections
Serum
Adipose Tissue
Bone Marrow
Adipocytes
Eating
Lipid Mobilization
Body Weight
Osteoprotegerin
Adipogenesis
Thermogenesis
Osteocalcin
Adiposity

Keywords

  • bone
  • gene expression
  • leptin
  • OB/OB mice
  • osteoporosis

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Orthopedics and Sports Medicine

Cite this

Central (ICV) leptin injection increases bone formation, bone mineral density, muscle mass, serum IGF-1, and the expression of osteogenic genes in leptin-deficient ob/ob mice. / Bartell, Shoshana M.; Rayalam, Srujana; Ambati, Suresh; Gaddam, Dhanunjaya R.; Hartzell, Diane L.; Hamrick, Mark W; She, Jin-Xiong; Della-Fera, Mary Anne; Baile, Clifton A.

In: Journal of Bone and Mineral Research, Vol. 26, No. 8, 01.08.2011, p. 1710-1720.

Research output: Contribution to journalArticle

Bartell, Shoshana M. ; Rayalam, Srujana ; Ambati, Suresh ; Gaddam, Dhanunjaya R. ; Hartzell, Diane L. ; Hamrick, Mark W ; She, Jin-Xiong ; Della-Fera, Mary Anne ; Baile, Clifton A. / Central (ICV) leptin injection increases bone formation, bone mineral density, muscle mass, serum IGF-1, and the expression of osteogenic genes in leptin-deficient ob/ob mice. In: Journal of Bone and Mineral Research. 2011 ; Vol. 26, No. 8. pp. 1710-1720.
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abstract = "Both central and peripheral leptin administrations reduce body weight, food intake, and adiposity in ob/ob mice. In this study we compared effects of intracerebroventricular (ICV) and subcutaneous (SC) administration of leptin on bone metabolism in the appendicular and axial skeleton and adipose tissue gene expression and determined the effects of ICV leptin on bone marrow gene expression in ob/ob mice. In experiment 1, leptin (1.5 or 0.38μg/d) or control was continuously injected ICV for 12 days. Gene expression analysis of femoral bone marrow stromal cells showed that expression of genes associated with osteogenesis was increased after ICV injection, whereas those associated with osteoclastogenesis, adipogenesis, and adipocyte lipid storage were decreased. In experiment 2, leptin was injected continuously ICV (0.0 or 1.5μg/d) or SC (0.0 or 10μg/d) for 12 days. In both experiments, regardless of mode of administration, leptin decreased body weight, food intake, and body fat and increased muscle mass, bone mineral density, bone mineral content, bone area, marrow adipocyte number, and mineral apposition rate. Serum insulin was decreased, whereas serum osteocalcin, insulin-like growth factor 1, osteoprotegerin, pyridinoline, and receptor activator of nuclear factor κB ligand concentrations were increased. In experiment 2, expression of genes in adipose tissue associated with apoptosis, lipid mobilization, insulin sensitivity, and thermogenesis was increased, whereas expression of genes associated with cell differentiation and maturation was decreased regardless of mode of administration. Thus ICV injection of leptin promotes expression of pro-osteogenic factors in bone marrow, leading to enhanced bone formation in ob/ob mice.",
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AU - Ambati, Suresh

AU - Gaddam, Dhanunjaya R.

AU - Hartzell, Diane L.

AU - Hamrick, Mark W

AU - She, Jin-Xiong

AU - Della-Fera, Mary Anne

AU - Baile, Clifton A.

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