Injections of leptin into rat ventromedial hypothalamus increase adipocyte apoptosis in peripheral fat and in bone marrow

Mark W. Hamrick, Mary Anne Della Fera, Yang Ho Choi, Diane Hartzell, Catherine Pennington, Clifton A. Baile

Research output: Contribution to journalArticle

54 Citations (Scopus)

Abstract

The accumulation of fat cells (adipocytes) in bone marrow is now thought to be a factor contributing to age-related bone loss. Women with osteoporosis have higher numbers of marrow adipocytes than women with healthy bone, and bone formation rate is inversely correlated with adipocyte number in bone tissue biopsies from both men and women. Adipogenic differentiation of bone marrow stromal cells increases with age, but the factors regulating populations of mature adipocytes are not well understood. Leptin is thought to regulate adipose tissue mass via its receptors in the ventromedial hypothalamus (VMH). We have therefore tested the hypothesis that stimulation of leptin receptors in the VMH regulates adipocyte number in bone marrow. Results indicate that unilateral twice-daily injections of leptin into the rat VMH for only 4 or 5 days cause a significant reduction in the number of adipocytes in peripheral fat pads and bone marrow and indeed eliminate adipocytes almost entirely from bone marrow of the proximal tibia. Osteoblast surface is not affected with leptin treatment. Apoptosis assays performed on bone marrow samples from control and treated rats have revealed a significant increase in protein concentration of the apoptosis marker caspase-3 with leptin treatment. We conclude that stimulation of leptin receptors in the VMH significantly decreases the adipocyte population in bone marrow, primarily through apoptosis of marrow adipocytes. Elimination of marrow adipocytes via this central pathway may represent a useful strategy for the treatment and prevention of osteoporosis.

Original languageEnglish (US)
Pages (from-to)133-141
Number of pages9
JournalCell and Tissue Research
Volume327
Issue number1
DOIs
StatePublished - Jan 1 2007

Fingerprint

Leptin
Adipocytes
Hypothalamus
Bone Marrow
Fats
Apoptosis
Injections
Osteoporosis
Leptin Receptors
Adipose Tissue
Bone and Bones
Age Factors
Population Dynamics
Osteoblasts
Tibia
Mesenchymal Stromal Cells
Osteogenesis
Caspase 3
Therapeutics
Biopsy

Keywords

  • Adipogenesis
  • Beta-adrenergic
  • Hypothalamus
  • Osteoblast
  • Rat (Sprague Dawley, male)

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Histology
  • Cell Biology

Cite this

Injections of leptin into rat ventromedial hypothalamus increase adipocyte apoptosis in peripheral fat and in bone marrow. / Hamrick, Mark W.; Della Fera, Mary Anne; Choi, Yang Ho; Hartzell, Diane; Pennington, Catherine; Baile, Clifton A.

In: Cell and Tissue Research, Vol. 327, No. 1, 01.01.2007, p. 133-141.

Research output: Contribution to journalArticle

Hamrick, Mark W. ; Della Fera, Mary Anne ; Choi, Yang Ho ; Hartzell, Diane ; Pennington, Catherine ; Baile, Clifton A. / Injections of leptin into rat ventromedial hypothalamus increase adipocyte apoptosis in peripheral fat and in bone marrow. In: Cell and Tissue Research. 2007 ; Vol. 327, No. 1. pp. 133-141.
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