Cardiometabolic syndrome (CMS) refers to a range of problems with the kidneys, cardiovascular system, metabolism, and inflammation, and it increases the risk of stroke, diabetes, and heart disease. Now researchers have linked a protein called clusterin to this disorder, which can involve excess body fat, high blood sugar, high blood pressure, abnormal cholesterol and is exacerbated by sedentary lifestyles and smoking. The study, which included human participants and a mouse model, has been reported in the journal Diabetes Care.
"Our goal was to discover new factors produced by the cells in fat tissue that have an impact on cardiometabolic disease. In particular, we wanted to identify those important to maintaining the framework of fat tissue, called the extracellular matrix, which becomes dysfunctional in obesity," explained the first author of the report Dr. David Bradley, an assistant professor in the Division of Endocrinology, Diabetes and Metabolism at The Ohio State University Wexner Medical Center.
Clusterin is an extracellular matrix protein, and fat cells in obese patients make too much of it. The protein is strongly linked to insulin resistance and has been connected to an increase in the risk of cardiovascular disease risk, high blood pressure, harmful cholesterol levels, fatty liver disease, and mortality. Insulin resistance can lead to type 2 diabetes, while obesity causes a range of health problems.
The researchers assessed gene expression, took measurements of biomarkers and performed correlation analysis on 54 obese patients and 18 that were lean, who were all undergoing elective surgery. Additional work was done in cultured cells and a mouse model that is prone to obesity-related complications. The team showed that clusterin derived from fat correlates with cardiovascular disease risk.
"This collaborative research is shedding new light on the importance of clusterin on cardiometabolic syndrome, which may eventually lead to developing new treatments for this life-threatening combination of diabetes, high blood pressure and obesity," said Dr. K. Craig Kent, dean of the Ohio State College of Medicine.
"Previously this protein clusterin has been mostly studied for its role in neurodegenerative diseases such as Alzheimer's but it now appears to have a broader role in human physiology and disease," he added.
"This study shows the hypothesis generation power of emerging systems biology approaches in discovering novel targets and mechanisms on complex diseases such as CMS. The clusterin protein is a key component of the extracellular matrix, so this work opens up a new vista to understand the role of clusterin in inter-cellular crosstalk of tissue microenvironments of various diseases, including diabetes, cancer, and neurodegeneration," said the co-corresponding author, Dr. Stephen T. C. Wong, professor and chair of the Department of Systems Medicine and Bioengineering at Houston Methodist.