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.
| Identifer | oai:union.ndltd.org:tamu.edu/oai:repository.tamu.edu:1969.1/ETD-TAMU-2561 |
| Date | 15 May 2009 |
| Creators | Baek, Kyunghwa |
| Contributors | Bloomfield, Susan A, Lupton, Joanne R |
| Source Sets | Texas A and M University |
| Language | en_US |
| Detected Language | English |
| Type | Book, Thesis, Electronic Dissertation, text |
| Format | electronic, application/pdf, born digital |
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