Vitamin D Status: Role of Muscle and Effect on Weight Loss
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Type
ThesisThesis type
Doctor of PhilosophyAuthor/s
Abboud, Myriam NassifAbstract
Vitamin D status has been shown to positively correlate with lean body mass. This led to the proposal that skeletal muscle could act as a variable pool of 25(OH)D, which is gradually released into the circulation to maintain vitaminD status. I showed that the capacity of differentiated ...
See moreVitamin D status has been shown to positively correlate with lean body mass. This led to the proposal that skeletal muscle could act as a variable pool of 25(OH)D, which is gradually released into the circulation to maintain vitaminD status. I showed that the capacity of differentiated C2 myotubes to take up and release 25(OH)D, was higher than other cells. C2 myotubes and primary myofibers were, for the first time, shown to express megalin and cubilin, endocytotic receptors for vitaminD binding protein (DBP), which binds nearly all 25(OH)D in the blood. I showed that muscle, but not fat, provides a large extravascular pool through which 25(OH)D circulates and so is protected from hepatic degradation. I provided evidence for a functional vitamin D receptor (VDR) in muscle. After incubation of myofibres in calcitriol, increased uptake of labeled 25(OH)D was observed. This was lacking in VDRKO myofibers. I demonstrated that muscle fibres express the parathyroid hormone (PTH) receptor and show a dose-dependent decrease in 25(OH)D uptake and increase in release by myofibres pre-incubated with even very low concentrations of PTH. My study showed that adequate vitaminD status was associated with significant weight and waist circumference reduction and beneficial effect on LDL-cholesterol
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See moreVitamin D status has been shown to positively correlate with lean body mass. This led to the proposal that skeletal muscle could act as a variable pool of 25(OH)D, which is gradually released into the circulation to maintain vitaminD status. I showed that the capacity of differentiated C2 myotubes to take up and release 25(OH)D, was higher than other cells. C2 myotubes and primary myofibers were, for the first time, shown to express megalin and cubilin, endocytotic receptors for vitaminD binding protein (DBP), which binds nearly all 25(OH)D in the blood. I showed that muscle, but not fat, provides a large extravascular pool through which 25(OH)D circulates and so is protected from hepatic degradation. I provided evidence for a functional vitamin D receptor (VDR) in muscle. After incubation of myofibres in calcitriol, increased uptake of labeled 25(OH)D was observed. This was lacking in VDRKO myofibers. I demonstrated that muscle fibres express the parathyroid hormone (PTH) receptor and show a dose-dependent decrease in 25(OH)D uptake and increase in release by myofibres pre-incubated with even very low concentrations of PTH. My study showed that adequate vitaminD status was associated with significant weight and waist circumference reduction and beneficial effect on LDL-cholesterol
See less
Date
2015-09-10Licence
The author retains copyright of this thesis. It may only be used for the purposes of research and study. It must not be used for any other purposes and may not be transmitted or shared with others without prior permission.Faculty/School
Sydney Medical SchoolDepartment, Discipline or Centre
Discipline of PhysiologyAwarding institution
The University of SydneyShare