Baek, Kyunghwa (2007-12). Bone loss during energy restriction: mechanistic role of leptin. Doctoral Dissertation. Thesis uri icon

abstract

  • Mechanical unloading and food restriction (FR) are leading causes of bone loss, which increase the risk of fracture later in life. Leptin, a 16kDa cytokine like hormone principally produced by white adipocytes, may be involved in bone metabolism with physiological or mechanical changes causing bone loss. The hypotheses of the first study were aimed at determining if serum leptin is reduced by unloading or FR. The serum leptin level reduced by unloading or by global FR, is associated with the decline in bone formation rate. It was conjectured that decreased serum leptin may be due to reduced adipocyte number/size and/or sympathetic nervous system (SNS) activation of betaadrenoreceptors with unloading or FR, inhibiting the release of leptin from adipocytes. In the second experiment, we tested whether leptin or beta-adrenoreceptor blockade attenuates bone loss during unloading and whether such an effect due to beta blockade is associated with changes in serum leptin level. Beta-blockade mitigated unloading induced reduction in serum leptin and also beta blockade was as effective as leptin administration in mitigating a reduction in cancellous bone mineral density with unloading through both stimulation of bone formation and suppression of resorption. It was previously demonstrated that energy restriction (ER) is a major contributor to the bone loss during global FR. In the third study, we tested whether beta- blockade attenuates bone loss during ER and whether such an effect is associated with changes in serum leptin level and leptin localization in bone tissues. Beta blockade attenuated the ER induced reduction in serum leptin level, cancellous bone mineral density and bone formation rate, and also abolished the ER induced increase in bone resorption. Reduction in leptin expression in bone marrow adipocytes observed with ER was attenuated by beta-blockade. Reduction in the number of cells (bone lining cells, osteocytes and chondrocytes in cartilage) which are stained positive for leptin was also attenuated by beta-blockade. Collectively, these data identify circulating leptin effects on preventing bone loss during mechanical unloading or energy restriction. Also beta blockade is associated with mitigating reduction in serum leptin and subsequently with mitigating reduction in bone mass with unloading or ER.
  • Mechanical unloading and food restriction (FR) are leading causes of bone loss, which
    increase the risk of fracture later in life. Leptin, a 16kDa cytokine like hormone
    principally produced by white adipocytes, may be involved in bone metabolism with
    physiological or mechanical changes causing bone loss. The hypotheses of the first study
    were aimed at determining if serum leptin is reduced by unloading or FR. The serum
    leptin level reduced by unloading or by global FR, is associated with the decline in bone
    formation rate. It was conjectured that decreased serum leptin may be due to reduced
    adipocyte number/size and/or sympathetic nervous system (SNS) activation of betaadrenoreceptors
    with unloading or FR, inhibiting the release of leptin from adipocytes.
    In the second experiment, we tested whether leptin or beta-adrenoreceptor blockade
    attenuates bone loss during unloading and whether such an effect due to beta blockade is
    associated with changes in serum leptin level. Beta-blockade mitigated unloading
    induced reduction in serum leptin and also beta blockade was as effective as leptin
    administration in mitigating a reduction in cancellous bone mineral density with
    unloading through both stimulation of bone formation and suppression of resorption. It
    was previously demonstrated that energy restriction (ER) is a major contributor to the bone loss during global FR. In the third study, we tested whether beta- blockade
    attenuates bone loss during ER and whether such an effect is associated with changes in
    serum leptin level and leptin localization in bone tissues. Beta blockade attenuated the
    ER induced reduction in serum leptin level, cancellous bone mineral density and bone
    formation rate, and also abolished the ER induced increase in bone resorption. Reduction
    in leptin expression in bone marrow adipocytes observed with ER was attenuated by
    beta-blockade. Reduction in the number of cells (bone lining cells, osteocytes and
    chondrocytes in cartilage) which are stained positive for leptin was also attenuated by
    beta-blockade. Collectively, these data identify circulating leptin effects on preventing
    bone loss during mechanical unloading or energy restriction. Also beta blockade is
    associated with mitigating reduction in serum leptin and subsequently with mitigating
    reduction in bone mass with unloading or ER.

publication date

  • December 2007