Assessment of Potential Novel Immune Biomarkers to Identify Obese Persons at Increased Risk for Cardiometabolic Disease

Elisa Fabbrini, M.D. Ph.D.

Project Overview:
Obesity is associated with a constellation of health complications, including diabetes, alterations in blood lipids, inflammation, and heart disease. However, not all obese individuals are at risk to develop these abnormalities, and approximately 30% of obese adults do not suffer from these complications at all.

The purpose of this study is to better understand the reasons why some but not all obese people develop metabolic complications and, if possible, to see if specific blood tests can help identify these people. This will be accomplished by studying two groups of obese subjects, who will be classified as metabolically-normal or metabolically-abnormal. These subjects will undergo careful metabolic testing in order to measure how their livers, muscles, and fat tissues metabolize sugar and fat. We will also collect blood, muscle and fat tissue from participants, in order to evaluate how glucose and lipids are handled in these specific tissues, and to evaluate the content and type(s) of inflammatory cells and molecules produced by these cells. We believe that metabolically-abnormal obese individuals will have inflammation in their fat tissue (“sick” adipose tissue), and that these inflammation markers will be released from fat tissue into the bloodstream. We hope this research will allow us to identify some specific bloodstream biomarkers in metabolically-abnormal and high-risk obese subjects

Progress Report:
In the first year of the study we found that metabolically abnormal obese subjects are more insulin-resistant than metabolically normal obese subjects. We also identified potential biomarkers that are specific of the metabolically abnormal obese phenotype.

In the second year of this study we will compare metabolically normal obese subjects to lean-healthy individuals to determine if there are differences in insulin action and fat metabolism. Information on the characteristics of the factors and metabolic pathways that distinguish lean-healthy, metabolically normal obese, and metabolically abnormal obese subjects will make it possible to get new insights into metabolic dysfunction and better characterize biomarkers to assess and monitor metabolic health.