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During a nearly decade-long study, researchers from the Ohio State College's College of Medicine, the Houston Methodist Research Institute and the Houston Methodist Cancer Center have linked clusterin protein – for the first time – to many different facets of the risk of cardiometabolic syndrome through its actions in the liver.
Cardiometabolic syndrome (CMS) is a group of conditions that occur together and increase the risk of heart disease, stroke and diabetes. These conditions include high blood pressure, hyperglycemia, excess body fat around the waist, and abnormal cholesterol or triglyceride levels. The risk of developing SMC is even greater in physically inactive or smoking patients.
The results of the study involving humans and mice are published online in the journal Diabetic treatments.
"Our goal was to discover new cell-derived factors in adipose tissue that impact cardiometabolic disease, specifically to identify those important for maintaining adipose tissue structure, called the extracellular matrix, which becomes dysfunctional. in obesity. "said the first author, Dr. David Bradley, badistant professor in the Division of Endocrinology, Diabetes and Metabolism at the Wexner Medical Center at Ohio State University and a member Ohio State Center for Diabetes and Metabolism Research.
The study found that a particular extracellular matrix protein called clusterin, which is overproduced by the fat cells of obese patients, is strongly related to insulin resistance. It is also linked to an increased risk of death and cardiovascular disease, high blood pressure, harmful cholesterol levels and liver steatosis.
Insulin resistance is a leading cause of type 2 diabetes, and obese patients usually have both metabolic and cardiovascular complications.
During the study, researchers performed gene expression, correlation badysis, and blood tests in 54 obese patients and 18 skinny patients undergoing elective surgery at the Wexner Medical Center. Ohio State. The study also focused on human cells and cultured mice likely to develop complications badociated with obesity.
"This collaborative research sheds new light on the importance of clusterin in the" cardiometabolic syndrome ", which could eventually lead to the development of new treatments for this potentially fatal badociation of diabetes, hypertension arterial and obesity, "said Dr. K. Craig Kent. Dean of the Ohio State College of Medicine. "Previously, this protein, clusterin, was primarily studied for its role in neurodegenerative diseases such as Alzheimer's disease, but it now appears to play a larger role in human physiology and disease."
CMS, which affects about 25% of the world's population, is now recognized as a disease entity by the World Health Organization and the American Society of Endocrinology. People with MSc are twice as likely to die from coronary artery disease and three times more likely to have a heart attack or stroke than those who do not have the syndrome.
"This study demonstrates the hypothesis-generating potential of emerging systems biology approaches by discovering new targets and mechanisms on complex diseases such as CMS Clusterin protein is a key component of extracellular matrix." This work therefore opens up a new perspective for understanding the role of clusterin in the cross-cellular cross-talk of tissue microenvironments of various diseases, including diabetes, cancer and neurodegeneration, "said the co-corresponding author, Dr. Stephen TC Wong, Professor and Director, Department of Systems Medicine and Bioengineering, Houston Methodist.
It is necessary to continue translational research involving murine models to learn more about the impact of clusterin on each of the CMS components and whether the administration of clusterin inhibitory antibodies inhibits the CMS.
"A critical problem has been to identify a unifying mechanism for the components of cardiometabolic syndrome," said Dr. Willa Hsueh, Principal Investigator, Director of the Center for Research on Diabetes and Metabolism and Professor of Medicine at the Division. of endocrinology, diabetes and metabolism in Ohio. Wexner Medical Center of the State. "Fat cells increase clusterin production as they grow into obesity.Clusterin could be a biomarker of the disease, as well as a therapeutic target to potentially prevent this disease."
This article has been republished from documents provided by the College of Medicine at Ohio State University. Note: Content may have changed for length and content. For more information, please contact the cited source.
Reference: Bradley et al. 2019. Clusterine alters hepatic sensitivity to insulin and clusterin adipocyte badociations to cardiometabolic risk. Diabetic treatments. https://doi.org/10.2337/dc18-0870.
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