The influence of leptin on trabecular architecture and marrow adiposity in GH-deficient rats.
The relationship between the degree of GH deficiency and impaired bone integrity is not simple and may be influenced by related endocrine variables. To test the hypothesis that elevated adiposity and hyperleptinaemia are contributory factors, we quantified femoral trabecular organisation in two models of GH deficiency with divergent degrees of adiposity - the moderately GH-deficient/hyperleptinaemic transgenic growth retarded (Tgr) rat and the profoundly GH-deficient/hypoleptinaemic dw/dw rat. Trabecular density (bone volume/total volume) and surface were reduced by 16% in dw/dw males, with a more fragmented trabecular lattice. This impairment was more pronounced in Tgr rats, with trabecular number and density further reduced (by an additional 21%) and relative surface (bone surface/bone volume), trabecular convexity (structural modal index) and fragmentation (pattern factor) increased. To establish whether the presence of obesity/hyperleptinaemia exacerbates bone impairment in GH deficiency, trabecular structure was assessed in dw/dw rats following diet-induced obesity (DIO). DIO had minimal effect on trabecular architecture, the increased concavity of trabecular surfaces being the only observable effect. Similarly, infusion of leptin into the tibial bone marrow cavity had no effect on trabecular organisation or tibial growth in wild-type rats. However, while this procedure also failed to affect trabecular architecture or osteoclast number in dw/dw rats, distal osteoblast surface was increased by 23%, marrow adipocyte number and epiphyseal plate width being reduced (by 40 and 5% respectively), without increasing caspase-3 immunoreactivity. These findings suggest that while leptin may directly inhibit adipocyte differentiation and favour osteoblast production, hyperleptinaemia makes only a minimal contribution to the impairment of bone structure in GH deficiency.
Department of Child Health, School of Medicine, Cardiff University, Cardiff, CF14 4XN, UK.
Bronwen A J
BA
Evans
Melanie J
MJ
Bull
Rebecca C
RC
Kench
Rebecca E
RE
Fox
Liam D
LD
Morgan
Amy E
AE
Stevenson
Evelien F
EF
Gevers
Mark J
MJ
Perry
Timothy
T
Wells
D017667:Adipocytes / Q000187:drug effects*; D050154:Adiposity / Q000187:drug effects*; D000704:Analysis of Variance; D000818:Animals; D015519:Bone Density / Q000187:drug effects; D001846:Bone Development / Q000187:drug effects*; D001853:Bone Marrow / Q000187:drug effects*; D001842:Bone and Bones / Q000187:drug effects*; D002454:Cell Differentiation / Q000187:drug effects; D013006:Growth Hormone / Q000172:deficiency*; D020738:Leptin / Q000494:pharmacology*; D008297:Male; D010006:Osteoblasts / Q000187:drug effects; D010010:Osteoclasts / Q000187:drug effects; D011863:Radioimmunoassay; D051381:Rats
D020738:Leptin; D013006:Growth Hormone