Anti-obesity effect of NO-releasing Nanomatrix

释放 NO 的纳米基质的抗肥胖作用

基本信息

批准号：
9762799
负责人：
Jeonga Kim
金额：
$ 7.43万
依托单位：
UNIVERSITY OF ALABAMA AT BIRMINGHAM
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-08-15 至 2021-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9762799
关键词：
Adipocytes Adipose tissue Adult Age Aging Agonist Atherosclerosis Biogenesis Biological Availability Blood Vessels Blood capillaries Blood flow Body Weight Body Weight decreased Brown Fat Cardiovascular Physiology Cell Differentiation process Cell Size Cell physiology Cells Cholesterol Disease Dyslipidemias Energy Metabolism Epidemic Exercise Fasting Fatty acid glycerol esters Gel Gene Expression Generations Glucose Glucose tolerance test Health Hormones Human Impairment Implant In Vitro Incubated Indirect Calorimetry Insulin Insulin Resistance Lead Lipids Lipolysis Measures Metabolic Diseases Metabolic dysfunction Metabolism Mitochondria Morphology Mus Nitric Oxide Nutrient Obesity Oxygen Peripheral Play Production Research Reverse Transcriptase Polymerase Chain Reaction Rodent Role Serum Technology Testing Therapeutic Tissues Triglycerides age related aged biomaterial compatibility blood glucose regulation cardiometabolism cell type diet and exercise endothelial dysfunction experimental study fatty acid oxidation glucose uptake immunocytochemistry improved in vivo insulin tolerance lifestyle intervention metabolic rate novel strategies novel therapeutics prevent recruit subcutaneous

项目摘要

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.

抽象的衰老与肥胖相关的代谢紊乱有关，主要是由于肥胖代谢率降低。在成年人中，这是一种世界性的流行病，会导致严重的健康问题，包括运动干预。和饮食，被推荐为最好的治疗方法，但结果往往并不理想，而且效果不佳。只是暂时的。运动和一氧化氮 (NO) 都会提高代谢率，从而有助于转化。通过增加线粒体数量和能量，将白色脂肪细胞转变为米色/浅色脂肪细胞（脂肪细胞褐变）这种有利的举动使身体代谢更多的脂肪并减少脂肪量。自从推广以来，还没有成功的治疗方法可以改善与年龄相关的心脏代谢疾病。 “褐变”可提高代谢率并改善心脏代谢功能，增强非非正常状态下的“褐变” 我们的研究表明，侵入性方式可能是预防与年龄相关的心脏代谢疾病的有效方法。研究小组开发了生物相容性NO释放纳米基质凝胶，可以在体内持续释放NO水平。因此，将释放NO的纳米基质凝胶植入白色脂肪组织中可能会引起脂肪细胞褐变。我们观察到，与释放 NO 的纳米基质凝胶一起孵育的细胞在体外诱导出棕色样脂肪细胞。这些结果表明，SubQ 施用释放 NO 的纳米基质凝胶是一种新颖的方法。通过促进脂肪细胞褐变来治疗与年龄相关的代谢功能障碍的治疗策略。为了检验假设；在目标 1 中，我们将确定皮下 (SubQ) 施用 NO- 的效果释放纳米基质凝胶对老年小鼠肥胖和胰岛素抵抗的影响；在目标 2 中，我们将阐明释放 NO 的纳米基质凝胶增强“褐变”AT 的机制将完成这些目标。提供了治疗与年龄相关的肥胖和心脏代谢疾病的新策略。