Cardiometabolic syndrome affects approximately 25 percent of the world’s population and is recognized as a disease entity by both the World Health Organization and the American Society of Endocrinology. It is defined by a cluster of conditions occurring together, including high blood pressure, high blood sugar, excess abdominal fat, and abnormal cholesterol or triglyceride levels, that collectively raise the risk of heart disease, stroke, and type 2 diabetes. People with cardiometabolic syndrome are twice as likely to die from coronary heart disease and three times more likely to experience a heart attack or stroke compared to those without the syndrome. Despite its prevalence and severity, a unifying biological mechanism had remained elusive. A new decade long study has now identified one.
How Clusterin Connects to Cardiometabolic Syndrome
Researchers at The Ohio State University College of Medicine, Houston Methodist Research Institute, and Houston Methodist Cancer Center have linked the protein clusterin to multiple components of cardiometabolic syndrome for the first time. The findings, published in the journal Diabetes Care, show that clusterin, which is overproduced by fat cells in obese patients, is strongly associated with insulin resistance, increased cardiovascular disease risk and mortality, high blood pressure, harmful cholesterol levels, and fatty liver disease.
Clusterin is a component of the extracellular matrix, the structural framework that supports fat tissue and becomes dysfunctional in obesity. As fat cells enlarge, they increase clusterin production. The study found this overproduction to be a consistent and measurable feature across the cardiometabolic syndrome disease cluster, suggesting the protein may serve as both a biomarker of disease and a potential therapeutic target.
What the Cardiometabolic Syndrome Study Involved
The research spanned nearly a decade and combined human and animal data. Researchers performed gene expression analyses, correlation studies, and blood measurements in 54 obese and 18 lean patients undergoing elective surgery at Ohio State’s Wexner Medical Center. The study also included human cultured cells and mouse models prone to developing obesity associated complications.
According to first author Dr. David Bradley, assistant professor in the Division of Endocrinology, Diabetes and Metabolism at Ohio State, the team set out specifically to identify new factors produced by fat tissue cells that influence cardiometabolic disease, with a focus on proteins involved in maintaining the extracellular matrix. Clusterin emerged as the most significant finding.
Cardiometabolic Syndrome and the Broader Role of Clusterin
Prior to this study, clusterin had been studied primarily in the context of neurodegenerative diseases such as Alzheimers. This research reveals a substantially broader role for the protein in human physiology, spanning metabolic, cardiovascular, and hepatic disease processes. According to Dr. K. Craig Kent, dean of the Ohio State College of Medicine, the findings may eventually lead to new treatments for the life threatening combination of diabetes, high blood pressure, and obesity that defines cardiometabolic syndrome.
Co corresponding author Dr. Stephen T. C. Wong of Houston Methodist noted that the discovery demonstrates the power of systems biology approaches in identifying novel targets in complex diseases, and that clusterin’s role in intercellular communication within tissue microenvironments may have implications across diabetes, cancer, and neurodegeneration.
Next Steps in Cardiometabolic Syndrome Research
Further translational research using mouse models is underway to better understand exactly how clusterin influences each individual component of cardiometabolic syndrome and whether antibodies that inhibit clusterin can suppress the syndrome’s progression. Lead researcher Dr. Willa Hsueh, director of the Diabetes and Metabolism Research Center at Ohio State, described the identification of a unifying mechanism for the components of cardiometabolic syndrome as a critical advance, one that positions clusterin as both a marker for early detection and a candidate for targeted intervention.
FOMAT conducts clinical research across multiple therapeutic areas including endocrinology and metabolic disease. To learn more about active studies, visit FOMAT’s patient studies page.
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