Leptin treatment induces loss of bone marrow adipocytes and increases bone formation in leptin-deficient ob/ob mice.
Normal mice and leptin-deficient ob/ob mice were treated with leptin to study effects on osteogenesis and adipogenesis in bone marrow. Leptin treatment significantly decreased bone marrow adipocyte size and number in ob/ob mice while increasing bone formation, BMC, and BMD. The results suggest that, in leptin-sensitive animals, the reduction in marrow adipocytes has positive effects on bone formation.


BACKGROUND
Adipocytes, osteoblasts, and osteoclasts have leptin receptors, and leptin can also affect bone metabolism indirectly through its receptors in the hypothalamus. We examined the effects of leptin treatment on bone formation, BMD, and marrow adipocyte population in normal mice and leptin-deficient ob/ob mice.


METHODS
At the age of 15 weeks, mice were implanted with Alzet osmotic pumps for subcutaneous delivery of treatment solutions (saline, 2.5 microg leptin/day, or 10 microg leptin/day) for 14 days at a delivery rate of 0.25 microl/h. Bone formation was assessed using fluorochrome labels, cell populations were quantified using histomorphometry, and bone densitometry was measured using DXA. We also used a Luminex Beadlyte assay system to quantify cell survival markers in bone marrow samples.


CONCLUSIONS
Results indicate that both doses of leptin decreased the number of marrow adipocytes in ob/ob mice by >20% (p < 0.05) compared with PBS-treated ob/ob mice. The decrease in adipocyte number with leptin treatment is accompanied by an increase in concentration of the apoptosis marker caspase-3 in bone marrow adipocytes and hematopoietic cells. Both leptin doses also significantly (p < 0.05) increased the percentage of fluorochrome-labeled tibial endosteal surface by >30% compared with PBS-treated ob/ob mice. Leptin treatment increased whole body BMC by >30% in the ob/ob mice receiving the highest leptin dose. Leptin treatment provided no increase in bone formation, BMC, or BMD in normal, leptin-replete mice.
Hamrick
Mark W
MW
Department of Cellular Biology and Anatomy, Medical College of Georgia, Augusta, Georgia 30912, USA. mhamrick@mail.mcg.edu
Della-Fera
Mary Anne
MA
Choi
Yang-Ho
YH
Pennington
Catherine
C
Hartzell
Diane
D
Baile
Clifton A
CA
D017667:Adipocytes / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D017209:Apoptosis; D015519:Bone Density; D001846:Bone Development; D001854:Bone Marrow Cells / Q000166:cytology* / Q000187:drug effects; D001842:Bone and Bones / Q000187:drug effects*; D053148:Caspase 3; D020169:Caspases / Q000096:biosynthesis; D002470:Cell Survival; D003720:Densitometry; D005260:Female; D005269:Femur / Q000187:drug effects; D006412:Hematopoietic Stem Cells / Q000187:drug effects; D007328:Insulin / Q000378:metabolism; D020738:Leptin / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use*; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D018613:Microscopy, Confocal; D010012:Osteogenesis / Q000187:drug effects; D013977:Tibia / Q000187:drug effects; D013997:Time Factors
D007328:Insulin; D020738:Leptin; C505409:Casp3 protein, mouse; D053148:Caspase 3; D020169:Caspases