Master of Science (MS)


Veterinary Medical Sciences - Pathobiological Sciences

Document Type



Obesity can have numerous detrimental consequences, namely metabolic syndrome, type 2 diabetes, cardiovascular disease, cancer, and Alzheimer’s disease. The pathogenesis and physiologic consequences of obesity are unknown, but they are often associated with increased inflammation and oxidative stress in both the body and in the brain. One factor that has been implicated in causing inflammation associated with a high fat diet is the enzyme NADPH oxidase, or NOX, specifically the subunit NOX2. Two studies were performed in order to assess the effects of a high fat diet in combination with a universal NOX2 deficiency and a NOX2 deficiency targeted to macrophages. The results of the first study indicate that the NOX2 knockout (NOX2KO) mice on a high fat diet do not experience all the deleterious metabolic and inflammatory effects in the body and brain to the same degree as wild-type mice. This suggests that a deficiency in NOX2 does offer protection from some of the deleterious effects of a high fat diet. It was also determined from the first study that NOX2 expression is localized to macrophages in the visceral adipose tissue. In order to target these macrophages, a second study was conducted. For this second study, a mouse model was genetically engineered with the intent of inhibiting NOX2 solely within macrophages. Similar to the first study, these macrophage-deficient NOX2 knockout (macNOX2KO) mice were placed on a high fat along with the NOX2-flox wild-type (WT-FL) mice. The results suggest that the macrophage-deficient NOX2 knockout mice were protected from the deleterious effects of a high fat diet. In summary, the deletion of NOX2 appears to offer a protective benefit against the deleterious effects of obesity in the context of a high fat diet. Specifically, the deletion of NOX2 in macrophages also offers this protection with the added benefit of targeting the deletion so as to not affect NOX2 functioning in other cells in the body.



Document Availability at the Time of Submission

Release the entire work immediately for access worldwide.

Committee Chair

Baker, David George