Treating Obesity and Cardiovascular Disease Via Genetic Manipulation of Skin Tissue
Using tissue nano-transfection to regulate BAT and increase 12,13-diHOME production to treat obesity, cardiovascular disease and type 2 diabetes.
Cardiovascular disease (CVD) is the leading cause of death across the US and worldwide and affects almost half of all adults in the US. CVD encompasses a number of conditions that affect the heart and vasculature. CVD can arise in response to multiple factors, including obesity. Obesity elevates the risk of CVD by increasing the development and severity of comorbidities such as hypertension, dyslipidemia, and diabetes. Exercise has been an important tool in combating CVD, obesity, and type 2 diabetes. Brown adipose tissue (BAT) releases the lipokine 12,13-diHOME in response to cold and exercise, which acts in an autocrine and endocrine manner to increase fatty acid uptake into both BAT and skeletal muscle, reducing circulating triglycerides and decreasing adiposity and insulin resistance, and also has a direct effect to improve cardiac function.
Patients suffering obesity or CVD are often told to build healthier habits such as getting more physical activity and eating a heart-healthy diet. However, many such patients suffer comorbidities that prevent them from participating in physical activity. One mechanism for exercise to combat obesity and CVD is via the release of the lipokine 12,13-diHOME. No current obesity or CVD treatment mimics the positive effects of exercise on the heart. Compositions and methods for treating CVD, obesity and type 2 diabetes through the regulation of BAT are needed.
Researchers at The Ohio State University have developed a method for treating obesity and CVD by increasing levels of lipokines, in particular 12,13-diHOME, through manipulation of the skin. Sustained upregulation of 12,13-diHOME by tissue nanotransfection (TNT) negated the adverse effects of a high-fat diet on body weight, adiposity, cardiac function and cardiac remodeling in mice. The novel method is especially useful for treating obesity, and CVD related to obesity, such as coronary artery disease, hypertension, stroke, atherosclerosis, heart failure and cardiac arrhythmias. The novel method may also be useful for treating an inflammatory disease, such as type 2 diabetes or nonalcoholic fatty liver disease.