Morbid obesity attenuates the skeletal abnormalities associated with leptin deficiency in mice

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   Figure 1

   Effects of morbid obesity on body weight (A), cumulative body weight change (B), cumulative food intake (C), abdominal white adipose tissue (WAT) weight (D), blood glucose (E), uterine weight (F), and serum osteocalcin (G) and CTx levels (H) in leptin-deficient ob/ob mice. Values are expressed as mean±s.e.m., n=10–11/group. ND, no data due to insufficient serum for measurement of CTx in pair-fed ob/ob mice. ^aDifferent from WT mice, P<0.05. ^bDifferent from ob/ob mice, P<0.05.
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   Figure 2

   Effects of morbid obesity on cancellous bone histomorphometry and marrow adiposity in distal femur metaphysis in leptin-deficient ob/ob mice. Shown are mineralizing perimeter (A, mineralizing perimeter/bone perimeter, M.Pm/B.Pm), mineral apposition rate (B, MAR), bone formation rate (C, bone formation rate/bone perimeter, BFR/B.Pm), osteoblast perimeter (D, osteoblast perimeter/bone perimeter, Ob.Pm/B.Pm), osteoclast perimeter (E, osteoclast perimeter/bone perimeter, Oc.Pm/B.Pm), cartilage area (F, cartilage area/tissue area, Cg.Ar/T.Ar), marrow adiposity (G, adipocyte area/tissue area, Ad.Ar/T.Ar), and adipocyte density (H, number of adipocytes/tissue area, N.Ad/T.Ar). Values are expressed as mean±s.e.m., n=10–11/group. ^aDifferent from WT mice, P<0.05. ^a*Different from WT mice, P<0.1. ^bDifferent from ob/ob mice, P<0.05.
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   Figure 3

   Representative photomicrographs of i) marrow adiposity in distal femur metaphysis in WT mouse (A), ob/ob mouse (B), and pair-fed ob/ob mouse (C), ii) cartilage remnants in distal femur epiphysis in WT mouse (D), ob/ob mouse (E), and pair-fed ob/ob mouse (F), and iii) declomycin label administered at study initiation in distal femur epiphysis in WT mouse (G), ob/ob mouse (H), and pair-fed ob/ob mouse (I).
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   Figure 4

   Effects of morbid obesity on cancellous bone histomorphometry and marrow adiposity in distal femur epiphysis in leptin-deficient ob/ob mice. Shown are mineralizing perimeter (A, mineralizing perimeter/bone perimeter, M.Pm/B.Pm), mineral apposition rate (B, MAR), bone formation rate (C, bone formation rate/bone perimeter, BFR/B.Pm), osteoblast perimeter (D, osteoblast perimeter/bone perimeter, Ob.Pm/B.Pm), osteoclast perimeter (E, osteoclast perimeter/bone perimeter, Oc.Pm/B.Pm), declomycin label perimeter (F, declomycin label perimeter/tissue area, declomycin L.Pm/T.Ar), cartilage area (G, cartilage area/tissue area, Cg.Ar/T.Ar), marrow adiposity (H, adipocyte area/tissue area, Ad.Ar/T.Ar), and adipocyte density (I, number of adipocytes/tissue area, N.Ad/T.Ar). Values are mean±s.e.m., n=10–11/group. ^aDifferent from WT mice, P<0.05. ^bDifferent from ob/ob mice, P<0.05.
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   Figure 5

   Effects of morbid obesity on cancellous bone histomorphometry and marrow adiposity in lumbar vertebra in leptin-deficient ob/ob mice. Shown are mineralizing perimeter (A, mineralizing perimeter/bone perimeter, M.Pm/B.Pm), mineral apposition rate (B, MAR), bone formation rate (C, bone formation rate/bone perimeter, BFR/B.Pm), osteoblast perimeter (D, osteoblast perimeter/bone perimeter, Ob.Pm/B.Pm), osteoclast perimeter (E, osteoclast perimeter/bone perimeter, Oc.Pm/B.Pm), declomycin label perimeter (F, declomycin label perimeter/tissue area, declomycin L.Pm/T.Ar), marrow adiposity (G, adipocyte area/tissue area, Ad.Ar/T.Ar), and adipocyte density (H, number of adipocytes/tissue area, N.Ad/T.Ar). Values are expressed as mean±s.e.m., n=10–11/group. ^aDifferent from WT mice, P<0.05. ^bDifferent from ob/ob mice, P<0.05.
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   Figure 6

   Effects of morbid obesity on expression of osteogenesis-related genes in tibia. The expressions of a panel of 84 osteogenesis-related genes in the tibia of WT mice (n=6), ob/ob mice (n=5), and ob/ob mice pair-fed to the WT mice (n=5) were determined using a mouse osteogenesis gene expression array. Left panel shows hierarchical clustering analysis of genes with significantly different gene expression. The magnitude of gene expression was represented by green and red bars, indicating decreased and increased expression respectively. The normalized mean fold change of ob/ob mice and pair-fed ob/ob mice relative to the WT mice was shown in the right panel. ^aDifferent from WT mice, P<0.05. ^bDifferent from ob/ob mice, P<0.05.

• © 2014 Society for Endocrinology