Date of Award

8-2014

Degree Type

Dissertation

Degree Name

Doctor of Philosophy

Major

Nutritional Sciences

Major Professor

Michael B. Zemel

Committee Members

Ling Zhao, Dallas R. Donohoe, Madhu Dhar

Abstract

Obesity is characterized by chronic oxidative and inflammatory stress, and adipose tissue is a significant source of inflammatory cytokines. Previous studies demonstrated that dairy products (rich in calcium and leucine) can alleviate obesity-associated inflammatory stress through suppression of 1, 25-dihydroxycholecalciferol (calcitriol) with calcium and the high leucine content in dairy. We have also shown leucine treatment increases anti-inflammatory adiponectin expression and decreases pro-inflammatory cytokines TNF-a [alpha], MCP-1, and IL-6 expression in adipocytes. Therefore, we sought to determine if these alterations in inflammatory cytokine production could have a functional effect on the inflammatory process, specifically monocyte – endothelial cell adhesion as this is one of the initial events of the inflammatory process. We demonstrate that leucine treatment of adipocytes reduces monocyte CD11b expression, endothelial cell ICAM-1 expression and, consequently, monocyte – endothelial cell adhesion in vitro while calcitriol exerted the opposite effects. Furthermore, plasma samples from obese individuals consuming high dairy diets (> [greater than] 3.5 servings/day) over a 12-week period reduced monocyte – endothelial cell adhesion, ex vivo. Recently, adipocyte derived microvesicles (ADMs) have been suggested to play a role in communication between adipose tissue and systemic circulation, so we sought to determine if adiponectin present on ADMs was responsible for the anti-inflammatory effects we have observed when treating adipocytes with leucine. Therefore, after adipocytes were treated for 48 hrs with leucine, the whole conditioned media (CM), purified ADMs, and remaining supernatant were applied to human peripheral blood to measure monocyte CD11b expression. Compared to control, leucine CM and the isolated ADMs both reduced monocyte CD11b expression while the supernatant fraction did not. Knocking down adiponectin with siRNA attenuated these effects, suggesting adiponectin associated with ADMs plays a role in mediating the anti-inflammatory effects we have observed. Collectively, these data suggest that dairy products can provide beneficial effects at reducing obesity-associated inflammation, and ADMs, in part, mediate some of these effects.

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