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. Indeed, approximately 30% of obese adults do not experience these complications at all.

The purpose of this study is to understand better the reasons why some but not all obese individuals develop metabolic complications and, if possible, to see if specific blood tests can help identify these individuals. 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 this 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 Abstract:
Although obesity is associated with multiple metabolic risk factors for cardiovascular disease, including
insulin resistance, diabetes, dyslipidemia, and non-infectious inflammation, about 30% of obese adults do not
have obvious metabolic abnormalities. We have found that excessive intrahepatic triglyceride (IHTG) content,
independent of body mass index (BMI), percent body fat, and visceral fat mass, is a robust marker of obese
persons who have metabolic dysfunction (insulin resistance in liver, muscle and adipose tissue and increased
VLDL-triglyceride [VLDL-TG] secretion rate). Conversely, obese persons who have normal IHTG content appear
to be resistant to developing obesity-related “cardiometabolic” complications. This observation has important
implications for health and life insurance providers because excess IHTG identifies people at increased risk for
future medical complications. However, the mechanisms responsible for the accumulation of ectopic fat
(IHTG) and the development of cardiometabolic abnormalities in some, but not all, obese persons are not
known. Read the full Progress Report.