Diet and Metabolic Inflammation

Obesity is a risk factor for several common cancers, including those of the breast, colon, liver, and pancreas. Proposed molecular links between obesity and these types of cancer include systemic inflammation, hyperinsulinemia, and changes in the serum concentrations of sex steroid hormones and adipokines. All of these are strongly linked to low-grade chronic inflammatory processes in expanded adipose tissue. The objective of this proposal is to test the hypothesis that adipose tissue inflammation can be reduced by the foods we eat.

Overweight or obese individuals with evidence of insulin resistance will be enrolled, until 16 have completed all study procedures. Enrolled subjects will be randomized to follow one of two healthy diets for 12 weeks to determine how each diet affects inflammation in the body and sugar and insulin levels in the blood. We will address the following specific aims: Primary specific aim: To investigate whether the consumption of either diet reduces the metabolic activation of adipose tissue macrophages (ATM) as assessed by quantifying the ATM cell surface expression (relative mean fluorescence intensity, rMFI) of the metabolic activation markers, CD36 and ABCA1. Secondary specific aim 1: To compare how each of the study diets affects endpoints downstream of metabolic activation of ATM, specifically (a) adipose tissue expression of the key pro-inflammatory cytokines tumor necrosis factor α (TNFα) and interleukins (IL)-1 beta and 6; (b) adipose tissue expression of the key anti-inflammatory adipokine, adiponectin; (c) systemic insulin sensitivity, as assessed by the Matsuda-DeFronzo Insulin Sensitivity Index (ISI), based on a 3-hour frequently sampled oral glucose tolerance test (FS-OGTT); and oral glucose tolerance, as assessed by measuring the total area-under-the-curve glucose in the FS-OGTT. Secondary specific aim 2: To compare the impact of each of the study diets on low-grade chronic systemic inflammation, as assessed by measuring the concentrations of high sensitivity C-reactive protein (hsCRP), IL-6, and total adiponectin in fasting plasma. Secondary specific aim 3: To assess dietary adherence in the two dietary intervention groups. Dietary adherence will be measured by a dietary adherence score (separately for each diet), based on repeated 4-day diet records completed by all participants in the study. Because all of our study endpoints are thought to be linked to the gut microbiota, and because the effects of diet may be mediated through changes in the gut microbiota, we will also collect stool samples from all participants before and after completing the study.