A link between pro-inflammatory molecules and illness progression has been found.
Obesity-related illnesses are a global pandemic, and as such, a particular focus of healthcare providers globally. A new study published online by a multi-institutional scientific team, lead by the Cincinnati Children’s Hospital, has reported the discovery of a previously unknown molecular driver that causes inflammation and contributes to obesity. In the study, published by the Journal of Clinical Investigation, researchers propose using a blood thinner to interrupt metabolic inflammation stemming from high-fat diets.
After introducing a high-fat diet to genetically engineered and normal mouse models, researchers found that an insoluble glycoprotein known as “fibrinogen” will bind with αMβ2-integrin white blood cell leukocytes known to contribute to diet-induced disease and obesity. According to the study’s authors, obesity activates a clotting system that converts fibrinogen into insoluble fibrin strands—this action produces an overabundance of leukocytes (which mature and turn into macrophage immune cells), causing excessive inflammation and tissue damage. Known as a precursor to cardiovascular issues and fatty liver disease, obesity and metabolic inflammation are linked to type 2 diabetes and cancer.
Flick and his colleagues used dabigatran, an FDA-approved blood thinner that blocks thrombin (an enzyme that promotes blood coagulation) in the treatment of the obese mice. In obese patients, said the announcement, thrombin can cause “hyper-coagulation” and produce tissue-damaging insoluble fibrin strands.
"Our findings provide a novel mechanistic link between elevated pro-coagulant function and fibrin-driven inflammation in adipose fat-storing tissue and the liver. These exacerbate obesity and its associated diseases," said Matthew Flick, Ph.D., Lead Study Investigator and Scientist in the Division of Experimental Hematology and Cancer Biology at Cincinnati Children's Hospital Medical Center. "We also provide the proof-of-concept that targeting thrombin or fibrin may limit pathologies in obese patients."
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