Rationale: Obesity is associated with several risk factors (for example, high blood sugar, poor insulin response and inflammation) that increase risk of developing cardiovascular disease and type 2 diabetes (T2DM). Obesity is also associated with abnormalities in the immune system and an increased risk of infection. Specific components of the diet such, as high dietary intake of fat and sugar, influence not only the development of obesity but also the immune system. It is unknown if the immune abnormalities associated with obesity in humans are due to: 1) excess body fat and/or 2) elevated blood sugar levels, often seen in obesity and/or 3) overall diet quality of an individual (for example high fat and/or high sugar intakes).

Research aims: The overall aim of this research proposal is to determine if diet or alterations in blood sugar levels independently affect inflammation and immune function in obese subjects. To achieve this goal, three objectives will be pursued: 1) to determine how obesity affects inflammation and immune function; 2) to determine how alterations in blood sugar levels affect inflammation and immune function; 3) to identify specific dietary factors that affect changes in immune function that are related to obesity.

Methodology: The study will recruit 4 groups of subjects that are similar in age and sex: lean subjects with normal blood sugar levels (NG); obese subjects with normal blood sugar levels (obese-NG); obese subjects who are pre-diabetic (as defined by having high blood sugar levels - but not high enough to be defined as having diabetes; GI); obese subjects who have type 2 diabetes (obese-T2DM).

Participants will consume a typical North American/Canadian diet that will maintain their weight for a 4-week time period (all food will be provided for the subjects by the Human Nutrition Clinical Research Unit at the University of Alberta). Immune system markers (inflammation in the blood and the response of immune cells) and cardiovascular disease markers (blood sugar and insulin) will be compared among the 4 groups of participants before and at the end of the study.

A stool sample will also be collected before and after the diet intervention to look at the effects of weight and blood sugar levels on the type of bacteria in the participants gut as part of a Stool Sub-study. Research has shown that weight and blood sugar levels may affect the type of bacteria in the participants gut, which in turn can affect immune function and health risk. This is not a part of the main study, and the participants stool sample will be analyzed in future research.

Outcomes: By comparing these four groups, the investigators will be able to gain an understanding of the immune complications associated with obesity alone (ie excess body fat) and the relationship between blood sugar levels and diet with immune complications. Thus, this study will identify dietary interventions to counteract the immune abnormalities associated with obesity, which may in turn have implications for affecting the risk of cardiovascular disease and T2DM associated with obesity.