Date of Award

8-2009

Degree Type

Dissertation

Degree Name

Doctor of Philosophy

Major

Nutritional Sciences

Major Professor

Michael B. Zemel,

Committee Members

Jung Han Kim, Guoxun Chen, Michael McEntee

Abstract

Oxidative stress and inflammatory stress have been implicated as a cause of tissue damage in multiple organ systems, leading to the development of chronic diseases such as obesity, diabetes, hypertony and atherosclerosis. They are also recognized as major factors contributing to the physiological process of aging. Previous studies have demonstrated that dietary calcium regulates reactive oxygen species production (ROS) production in adipocytes in vitro and in vivo, and inhibits adipocyte-derived inflammatory cytokine expression by suppression of calcitriol. In addition, high calcium diets modulate energy metabolism and partitioning between adipose tissue and muscle resulting in a decrease in fat storage and an increase in fat oxidation in muscle. Providing calcium in form of dairy appears to cause greater effects than supplemental calcium in both mice and humans, most likely mediated by additional components in dairy products such as branched-chain amino acids (BCAA) and angiotensin converting enzyme inhibitor (ACEi) peptides. In consideration of the multiple effects of dietary calcium and other components of dairy on adipocyte and muscle metabolism, a high density oligonucleotide microarray approach was used to identify common and differential pathways related to energy metabolism, inflammation and oxidative stress in adipose and muscle tissue in response to milk and milk components. In addition, considering the protective role of dietary calcium against oxidative and inflammatory stress, which otherwise accelerate the process of aging, a lifespan study in a mouse model of diet- induced obesity was conducted to evaluate the effects of dietary calcium from both non-dairy and dairy sources on mouse lifespan and on lifespan-related biomarkers.

The results of this research confirm that calcium and BCAA contribute to the alteration of energy partitioning between adipose tissue and muscle and provide new evidence for calcium independent effects of BCAA and ACEi in energy metabolism and inflammation. Further, present data demonstrate that milk diet attenuates adiposity, protects against muscle loss and reduces oxidative and inflammatory stress. Although these did not alter maximum lifespan, they significantly suppressed early mortality.

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