In a decade-long study, researchers from The Ohio State University College of Medicine, Houston Methodist Cancer Center, and Houston Methodist Research Institute, for the first time, have linked ‘protein clusterin’ to various risks of cardiometabolic syndrome (CMS) due to its action in the liver.
CMS is a group of conditions occurring together that increase an individual’s risk of stroke, heart disease, and even diabetes. Some of these conditions are high blood pressure, excess abdominal fat, high blood sugar, and abnormal levels of cholesterol and triglycerides. CMS risk is even higher in people who smoke or are inactive.
The researchers carried out the study in mice and humans, and findings are detailed in research paper published in the journal Diabetes Care.
The study aimed at discovering new factors generated by the cells in fat tissues that generally have an impact on cardiac and metabolic diseases. According to first author Dr. David Bradley, the team particularly wanted to identify the factors key to maintaining fat tissue framework known as the extracellular matrix, which is likely to be dysfunctional in obesity.
The study discovered that a specific extracellular matrix protein, ‘clusterin’, which is overproduced from the fat cells of obese patients, is strongly associated with insulin resistance. It is further related to increased risk of high blood pressure, cardiovascular disease, fatty liver disease, harmful cholesterol levels and mortality.
Insulin resistance is one of the major causes of Type 2 Diabetes, while obese patients usually face metabolic as well as cardiovascular complications.
The team performed blood measurements, correlation analyses, and gene expression in the study involving 54 patients with obesity and 18 lean patients undergoing elective surgery. It also involved mice and human cultured cells prone to developing obesity-related complications.
Dr. K. Craig Kent from the Ohio State College of Medicine said that the collaborative research sheds light on the importance protein clusterin on CMS which may ultimately lead to the development of effective treatments for the life-threatening combination of obesity, high blood pressure, and type 2 diabetes.
In previous studies, this protein has been always examined for its role in neurodegenerative diseases like Alzheimer’s. Now, it appears to have larger impact on human physiology and diseases.
Further research is required to better understand the impact of clusterin on each of the CMS conditions and whether administrating antibodies that inhibit clusterin also inhibit these conditions.