Researchers make groundbreaking discovery in the fight against obesity, type 2 diabetes
[Apr. 4, 2023: JD Shavit, The Brighter Side of News]
Team of researchers has made a groundbreaking discovery in the fight against obesity, type 2 diabetes, and cardiovascular disease.(CREDIT: Creative Commons)
Cardiovascular diseases are the leading cause of death worldwide and have a significant negative influence on patient quality of life and disability. Endothelial dysfunction contributes significantly to the development and progression of cardiovascular pathophysiology and is considered an early predictor of cardiovascular events.
A team of researchers from Ohio University’s Heritage College of Osteopathic Medicine has made a groundbreaking discovery in the fight against obesity, type 2 diabetes, and cardiovascular disease. The study, titled “Endothelial-Specific Expression of CIDEC Improves High-Fat Diet–Induced Vascular and Metabolic Dysfunction,” was recently published in Diabetes and focuses on vascular function and its association with metabolic diseases.
According to the study, endothelial cells play a major role in maintaining vascular function, including blood pressure. Endothelial dysfunction, which is common in obese individuals, has been linked to the progression of insulin resistance, diabetes, cardiovascular disease, and other metabolic diseases.
The team of researchers discovered that the human-CIDEC gene, which was previously identified as a fat-associated protein in adipocytes, is abundantly expressed in endothelial cells and regulates their function.
To conduct the study, the team generated humanized transgenic mice that expressed the human CIDEC transgene specifically in endothelial cells. These mice were fed a high-fat diet to mimic the obese state in humans. The results were astounding, as the humanized transgenic mice showed protection against high-fat diet-induced insulin resistance and displayed lower circulating lipid levels.
“This study truly shows the power of teamwork and collaboration,” said Vishwajeet Puri, Ph.D., professor of biomedical sciences and co-director of the Diabetes Institute. “It is thrilling to see the diversity of people contributing to advance science and medicine. We have researchers on this study with diverse ethnic backgrounds, with all sorts of experience levels ranging from established scientists to undergraduate students, and with all types of areas of expertise such as cardiologists, cell biologists, physiologists, and more.”
Bijinu Balakrishnan, Ph.D., a scientist in Puri’s lab who led the study, received the American Heart Association Postdoctoral Fellowship award for two years to work on identifying the role of CIDEC protein in vascular functions.
Generation of E-CIDECtg mice. A: Schematic representation of the generation of E-CIDECtg mice. (CREDIT: Diabetes)
Prior to joining Puri’s laboratory in 2018, Balakrishnan received his Ph.D. from Myongji University in the Republic of Korea in 2012, where his primary focus was to elucidate the biosynthetic pathway of fungal polyketides. While pursuing his doctoral degree, he published nine papers and found a position at the Mayo Clinic to pursue his postdoctoral training to study the role of pancreatic lipases in acute pancreatitis.
“This is a very impactful study, and we have moved in the right direction to find a way to reduce cardiovascular diseases,” Puri said. “When looking at diseases like diabetes and obesity, you cannot disassociate them from cardiovascular disease since they are all closely associated. Discoveries like this one allow us to not only manage the disease but work to cure it and help fight any related disorders.”
CIDEC interacts with VEGFA and VEGFR2. Representative confocal image (0.2-µm Z slice) showing colocalization of endogenous CIDEC (green), VEGFA (red), and VEGFR2 (magenta), revealed by immunolabeling, in VEGFA-stimulated HUVECs. (CREDIT: Diabetes)
Puri is the Osteopathic Heritage Foundation Ralph S. Licklider, D.O., Endowed Professor in Diabetes at the Heritage College. He is recognized for identifying the CIDE proteins and their role in pathogenesis and pathophysiology of obesity, type 2 diabetes and cardiovascular disease.
Other studies on Endothelial dysfunction and diabetes
Endothelial dysfunction is a well-known contributor to the pathogenesis of diabetes and its associated complications. In recent years, there have been several studies on the topic, exploring the mechanisms of endothelial dysfunction in diabetes and potential treatments.
E-CIDECtg mice showed improved vascularization in different tissues. A: Representative image of capillary branches sprouting from visceral adipose tissue explant of E-CIDECtg and FLC male mice fed HFD for 12 weeks. (CREDIT: Diabetes)
One study published in the journal Diabetes Care in 2016 examined the relationship between endothelial dysfunction and diabetes in African Americans. The study found that African Americans with diabetes had higher levels of endothelial dysfunction compared to those without diabetes, and that the severity of endothelial dysfunction was associated with the duration of diabetes.
Another study published in the journal Cardiovascular Diabetology in 2019 investigated the effects of sodium-glucose cotransporter 2 (SGLT2) inhibitors on endothelial function in patients with type 2 diabetes. SGLT2 inhibitors are a class of drugs used to treat diabetes by blocking the reabsorption of glucose in the kidneys, leading to increased urinary excretion of glucose. The study found that treatment with SGLT2 inhibitors improved endothelial function in patients with type 2 diabetes.
CIDEC rescues tube formation with knocked-down VEGFA, and E-CIDECtg mice are protected against HFD-impaired vasodilation. (CREDIT: Diabetes)
In addition, there have been studies exploring the role of various biomarkers in endothelial dysfunction in diabetes. For example, a study published in the journal Diabetes in 2015 examined the relationship between the biomarker asymmetric dimethylarginine (ADMA) and endothelial dysfunction in patients with type 1 diabetes. The study found that higher levels of ADMA were associated with worse endothelial dysfunction in these patients.
The study was funded by the National Heart, Lung, and Blood Institute and included collaboration with researchers Shakun Karki and Noyan Gokce from Boston University School of Medicine and Analia S Loria from the University of Kentucky in Lexington. Members of the research team from Ohio University’s Heritage College also include Abhishek Gupta, Vishva M. Sharma, Mark Slayton, Rabia Basri, Kailey Gentner, Chloe Becker, Harrison Muturi, and Endowed Eminent Research Chair Sonia M. Najjar.
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