Anti-obesity effect of NO-releasing Nanomatrix

摘要

ABSTRACT Aging is associated with obese-associated metabolic disorders mainly due to the reduced metabolic rate. Obesity in adults is a world-wide epidemic, and causes serious health problems. Lifestyle intervention, including exercise and diet, is recommended for the best treatment. However, the results are often unsatisfactory, and the effect is only temporary. Both exercise and nitric oxide (NO) increase metabolic rate, which contributes to converting white adipocyte to beige/brite adipocyte (browning of adipocyte) by increasing mitochondrial number and energy production. This favorable move makes the body metabolize more fat and reduce fat mass. However, there is no successful treatment available to improve age-associated cardiometabolic disorders. Since promotion of “browning” increases metabolic rate and improve cardiometabolic functions, enhancing “browning” in a non- invasive manner may be an efficient way of preventing age-associated cardiometabolic diseases. Our research team developed biocompatible NO-releasing nanomatrix gel, which can release sustained levels of NO in vivo. Therefore, implanting NO-releasing nanomatrx gel into white adipose tissue may induce browning of adipocyte. We observed that cells incubated with NO-releasing nanomatrix gel induces brown-like adipocytes in vitro. From these results, we hypothesize that SubQ administration of a NO-releasing nanomatrix gel is a novel therapeutic strategy to treat age-related metabolic dysfunction by promoting browning of adipocytes. To test the hypothesis; in the aim 1, we will determine the effect of subcutaneous (SubQ) administration of a NO- releasing nanomatrix gel on obesity and insulin resistance in aged mice; in the aim 2, we will elucidate the mechanisms by which NO-releasing nanomatrix gel enhances “browning” AT. Completion of these aims will provide a novel strategy to treat age-associated obesity and cardiometabolic diseases.