One proposed mechanism linking obesity with an increased risk of breast, colon, liver and pancreatic cancer is the low-grade chronic inflammation found in adipose tissue. This inflammation is also a concern for other chronic diseases, most importantly type 2 diabetes, given that the low-grade chronic inflammatory processes in expanded adipose tissue are thought to be a major factor in the development of insulin resistance.
Macrophages are a major effector cell type in adipose tissue inflammation. The prevailing paradigm is that adipose tissue macrophages undergo a phenotypic switch towards a more pro-inflammatory phenotype when adipose tissue expands, though the pro-inflammatory phenotype differs from classically activated macrophages. Currently the cause of this phenotypic switch is unknown. Preliminary evidence suggests that exposure of macrophages to high physiological doses of glucose, insulin, and free fatty acids triggers inflammatory pathways within the cells, which may contribute to the phenotypic switch in adipose tissue macrophages. This model, which we call ‘metabolic activation’ of macrophages, is based on a recent translational research project conducted in collaboration with Dr. Lev Becker, University of Chicago, published in Cell Metabolism. The AIM Study investigates whether changes in diet composition to minimize the exposure of adipose tissue macrophages to hypothesized pro-inflammatory factors can reverse the metabolic activation of adipose tissue macrophages. Reduced metabolic activation would in turn be expected to be associated with reduced expression of pro-inflammatory mediators in adipose tissue (i.e., reduced ‘inflammation’) and possibly improved insulin sensitivity.
This parallel design, randomized controlled pilot trial compares the impact of the newly designed Anti-Inflammatory Milieu (AIM)-diet with that of a healthy control diet consistent with the 2010 “Dietary Guidelines for Americans”. Study procedures, conducted at baseline and again after the 12-week dietary intervention, include assessment of body weight and composition (by DEXA-scan), a fasting blood draw, a frequently sampled oral glucose tolerance test to assess glucose tolerance and insulin sensitivity, a stool collection, and an adipose tissue biopsy to assess measures of metabolic activation in adipose tissue macrophages.
Status: In progress (as of April 2016), completion expected by fall of 2016