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Document Type

Dissertation - University Access Only

Award Date


Degree Name

Doctor of Philosophy (PhD)


Health and Nutritional Sciences

First Advisor

Igor N. Sergeev


Vitamin D and calcium are not only essential for bone health, but can also participate in regulation of body fat mass via induction of apoptosis in adipose tissue. The hormonal form of vitamin D, 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), induces Ca2+ signal associated with activation of Ca 2+-dependent apoptotic proteases in mature adipocytes. However, whether an increase in dietary vitamin D and calcium intakes can induce adipocyte apoptosis in obese adipose tissue in vivo has not been established. Obesity can be detrimental to bone health, however the effects of increased vitamin D and calcium intakes on bone status in obesity are not known. In these studies, a mouse diet-induced obesity (DIO) model was used to investigate the role of vitamin D and calcium in regulation of adiposity and bone status. Male mice were fed high vitamin D3 (10000 IU/kg), high calcium (1.2%), and high vitamin D3 plus high calcium diets containing 60% energy as fat for 10 weeks. DIO mice fed high vitamin D3, high Ca, and high D3 plus high Ca diets demonstrated a decreased body weight gain and fat mass, improved markers of adiposity and vitamin D status (plasma concentrations of glucose, insulin, adiponectin, 25(OH)D, 1,25(OH)2D,parathyroid hormone), but an increased plasma Ca2+. High vitamin D3 and Ca intakes were associated with induction of apoptosis and activation of Ca2+-dependent apoptotic proteases, calpain and caspase-12, in adipose tissue of DIO mice. The combination of vitamin D3 and Ca was more effective than vitamin D3 alone or Ca alone in decreasing adiposity. DIO mice demonstrated a lower bone mineral content (BMC) and relative bone weight compared with the normal control, while collagen (hydroxyproline) content was not changed. High vitamin D3 and Ca intakes significantly increased BMC (Ca and P) and relative bone weight in DIO mice, which was accompanied by an increase in 1,25(OH)2D concentration and a decrease in parathyroid hormone (PTH) and osteocalcin concentrations in blood. In conclusion, the findings obtained indicate that increased vitamin D and Ca intakes activate Ca2+-mediated apoptotic pathway in adipose tissue leading to a decreased fat mass in DIO. The results also demonstrate that high vitamin D and Ca intakes are effective in increasing mineral content in the growing bone of obese mice and that the hormonal mechanisms of this effect involves the vitamin D – PTH axis. Vitamin D and Ca supplementation can represent an effective, safe and affordable approach for the prevention and treatment of obesity and obesity-related bone disorders.

Library of Congress Subject Headings

Vitamin D in human nutrition
Calcium in human nutrition


Includes bibliographical references (pages 126-151)



Number of Pages



South Dakota State University


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