Anti-obesity effect of NO-releasing Nanomatrix

释放 NO 的纳米基质的抗肥胖作用

• 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
• 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

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.

摘要 衰老与肥胖相关的代谢紊乱有关，主要是由于代谢率降低。肥胖 在成人中是一种世界性的流行病，并导致严重的健康问题。生活方式干预，包括锻炼 和饮食，是最好的治疗建议。然而，结果往往不尽如人意，而且效果 只是暂时的运动和一氧化氮（NO）都能提高代谢率，这有助于将 通过增加线粒体数量和能量使白色脂肪细胞变为米色/浅褐色脂肪细胞（脂肪细胞的布朗宁） 生产这种有利的举动使身体代谢更多的脂肪和减少脂肪量。不过有 没有成功的治疗方法可以改善年龄相关的心脏代谢疾病。自从推广 “布朗宁”增加代谢率并改善心脏代谢功能，在非代谢性环境中增强“布朗宁”。 有创性治疗可能是预防年龄相关性心脏代谢疾病的有效方法。我们的研究 研究小组开发了生物相容的NO释放纳米基质凝胶，它可以在体内释放持续水平的NO。 因此，将释放NO的纳米基质凝胶植入白色脂肪组织中可诱导脂肪细胞的布朗宁。 我们观察到，细胞与NO释放纳米基质凝胶孵育诱导棕色样脂肪细胞在体外。从 根据这些结果，我们假设SubQ施用NO释放纳米基质凝胶是一种新的 通过促进脂肪细胞的布朗宁来治疗年龄相关的代谢功能障碍的治疗策略。 为了检验这一假设，在目标1中，我们将确定皮下（SubQ）给予NO-1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;在目的2中，我们将阐明 NO释放纳米基质凝胶增强“布朗宁”AT的机制。实现这些目标将 提供了一种治疗与年龄相关的肥胖症和心脏代谢疾病的新策略。