TY - JOUR
T1 - Body mass influences cortical bone mass independent of leptin signaling
AU - Iwaniec, U. T.
AU - Dube, M. G.
AU - Boghossian, S.
AU - Song, H.
AU - Helferich, W. G.
AU - Turner, R. T.
AU - Kalra, S. P.
N1 - Funding Information:
This work was supported by grants from the National Institute of Health (DK 37273 and 27372 to S.P. Kalra and AA 011140 to R.T. Turner) and the Center for Healthy Aging Research, Oregon State University (to U.T. Iwaniec).
PY - 2009/3
Y1 - 2009/3
N2 - Obesity in humans is associated with increased bone mass. Leptin, a hormone produced by fat cells, functions as a sentinel of energy balance, and may mediate the putative positive effects of body mass on bone. We performed studies in male C57Bl/6 wild type (WT) and leptin-deficient ob/ob mice to determine whether body mass gain induced by high fat intake increases bone mass and, if so, whether this requires central leptin signaling. The relationship between body mass and bone mass and architecture was evaluated in 9-week-old and 24-week-old WT mice fed a regular mouse diet. Femora and lumbar vertebrae were analyzed by micro computed tomography. In subsequent studies, slowly and rapidly growing ob/ob mice were injected in the hypothalamus with a recombinant adeno-associated virus containing the leptin gene (rAAV-lep) or a control vector, rAAV-GFP (green fluorescent protein). The mice were maintained on a regular control diet for 5 or 7 weeks and then subdivided into groups and either continued on the control diet or fed a high fat diet (45% of kcal from fat) for 8 weeks. In the WT mice, femoral and vertebral bone mass was positively correlated with body mass (Pearson's r = 0.65-0.88 depending on endpoint). rAAV-lep therapy dramatically decreased body mass (- 61%) but increased femur length. However, in the distal femur and lumbar vertebra, rAAV-lep therapy reduced cancellous bone volume/tissue volume, trabecular number and trabecular thickness, and increased trabecular spacing. The high fat diet increased body mass, irrespective of vector treatment. Total femur bone volume, length, cross-sectional volume, and cortical volume and thickness were increased in mice with increased body mass, independent of rAAV treatment. In the distal femur, increased body mass had no effect on cancellous architecture and there were no vector × body mass interactions. In WT mice, increased body mass resulted in increased (+ 33%) vertebral cancellous bone volume/tissue volume. Increased body mass had minimal independent effect on cancellous vertebral bone mass in ob/ob mice. Taken together, these findings suggest that increased body mass has a positive effect on femur cortical bone mass that is independent of leptin signaling.
AB - Obesity in humans is associated with increased bone mass. Leptin, a hormone produced by fat cells, functions as a sentinel of energy balance, and may mediate the putative positive effects of body mass on bone. We performed studies in male C57Bl/6 wild type (WT) and leptin-deficient ob/ob mice to determine whether body mass gain induced by high fat intake increases bone mass and, if so, whether this requires central leptin signaling. The relationship between body mass and bone mass and architecture was evaluated in 9-week-old and 24-week-old WT mice fed a regular mouse diet. Femora and lumbar vertebrae were analyzed by micro computed tomography. In subsequent studies, slowly and rapidly growing ob/ob mice were injected in the hypothalamus with a recombinant adeno-associated virus containing the leptin gene (rAAV-lep) or a control vector, rAAV-GFP (green fluorescent protein). The mice were maintained on a regular control diet for 5 or 7 weeks and then subdivided into groups and either continued on the control diet or fed a high fat diet (45% of kcal from fat) for 8 weeks. In the WT mice, femoral and vertebral bone mass was positively correlated with body mass (Pearson's r = 0.65-0.88 depending on endpoint). rAAV-lep therapy dramatically decreased body mass (- 61%) but increased femur length. However, in the distal femur and lumbar vertebra, rAAV-lep therapy reduced cancellous bone volume/tissue volume, trabecular number and trabecular thickness, and increased trabecular spacing. The high fat diet increased body mass, irrespective of vector treatment. Total femur bone volume, length, cross-sectional volume, and cortical volume and thickness were increased in mice with increased body mass, independent of rAAV treatment. In the distal femur, increased body mass had no effect on cancellous architecture and there were no vector × body mass interactions. In WT mice, increased body mass resulted in increased (+ 33%) vertebral cancellous bone volume/tissue volume. Increased body mass had minimal independent effect on cancellous vertebral bone mass in ob/ob mice. Taken together, these findings suggest that increased body mass has a positive effect on femur cortical bone mass that is independent of leptin signaling.
KW - Body mass
KW - Obesity
KW - Osteoporosis
KW - Peak bone mass
KW - Weight
KW - μCT
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U2 - 10.1016/j.bone.2008.10.058
DO - 10.1016/j.bone.2008.10.058
M3 - Article
C2 - 19095090
AN - SCOPUS:59649106047
SN - 8756-3282
VL - 44
SP - 404
EP - 412
JO - Bone
JF - Bone
IS - 3
ER -