Cold Induced Changed in Human Subcutaneous White Adipose

寒冷引起的人皮下白色脂肪的变化

• 批准号: 9008664
• 负责人: Philip A Kern
• 金额: $ 51.89万
• 依托单位: UNIVERSITY OF KENTUCKY
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-21 至 2018-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9008664
• 关键词: Abbreviations; Acute; Address; Adipocytes; Adipose tissue; Adrenergic Agents; Adrenergic Receptor; Adult; Area; Basal metabolic rate; Biological Response Modifiers; Brown Fat; Catecholamines; Cyclic AMP-Dependent Protein Kinases; Data; Development; Diabetes Mellitus; Energy Metabolism; Exposure to; Genes; Health; Heart Diseases; Human; Image; Immune; Immune system; Inflammation; Inflammatory; Insulin; Insulin Resistance; Iodothyronine Deiodinase; Lead; Link; Lipids; Lipolysis; Mammals; Mediating; Mediator of activation protein; Metabolic syndrome; Mitochondria; Mus; Neck; OGTT; Obesity; Phenotype; Physiological; Positron-Emission Tomography; Process; Property; Proteins; Regulation; Research; Resistance; Rodent; Role; Seasons; Societies; Source; Stem cells; Sympathetic Nervous System; Temperature; Thermogenesis; Tissues; Triglycerides; Vertebral column; Weather; adrenergic; base; cold temperature; glucose uptake; improved; in vivo; interest; macrophage; prevent; receptor; response; subcutaneous

 DESCRIPTION (provided by applicant): The recent rediscovery of human brown adipose tissue through PET-CT has initiated more research on thermogenesis and defense defense against obesity. Many studies have demonstrated that white adipose tissue (WAT) in mice has the ability to upregulate its thermogenic capacity and become "beige". No studies have demonstrated browning of typical human WAT depots, except for our recent studies. We have recently examined the subcutaneous (SC) WAT of humans and found a considerable ability to upregulate UCP1 and other mitochondrial genes in response to cold and to seasons, and we have demonstrated this phenomenon with human adipocytes in culture. The seasonal changes in WAT are of particular interest, since this indicates a physiologic response to colder weather, without provocative and unphysiologic experimental conditions. In addition, we found that obese humans with a high SC WAT macrophage burden do not upregulate SC WAT UCP1 as well, suggesting that adipose inflammation inhibits the increased thermogenic capacity of WAT. A number of immune-mediate functions are involved in this process. Based on these data, we propose the following hypotheses. Hypothesis 1. Repeated exposure to cold temperatures will amplify changes in human subcutaneous WAT beiging. These beiging effects are seen acutely, in response to seasons and involve an activation of immune mediators. Hypothesis 2. The beiging of SC WAT involves an acute increase in adipose tissue immune mediators, which may be a source of catecholamines that activate protein kinase A (PKA). This process is inhibited by β-blockers in vivo. Hypothesis 3. Obese insulin resistant subjects are resistant to cold induced changes in WAT due to the proinflammatory milieu which inhibits local mediators of beiging. Hypothesis 4. Cold- and season-induced changes in SC WAT will lead to functional changes in the tissue, characterized by increased mitochondrial uncoupling, increased TG turnover (lipolysis) and increased resting metabolic rate. PUBLIC HEALTH: Obesity is closely linked with insulin resistance, diabetes and heart disease. Recent studies have focused on brown adipose tissue in humans, which may increase energy expenditure and help prevent obesity. This proposal examines the extent to which subcutaneous white adipose can become brown-like, or beige. We will determine whether this process is inhibited by the inflammatory state of obesity/metabolic syndrome, and we will characterize the effects of cold on adipose triglyceride turnover.

 描述（由适用提供）：最近通过PET-CT重新发现了人类棕色脂肪组织，从而对肥胖的热生成和防御防御进行了更多研究。许多研究表明，小鼠中的白脂肪组织（WAT）具有上调其热能能力并变为“米色”的能力。除我们最近的研究外，没有研究表明典型的人类水沉积物的褐变。我们最近检查了人类的皮下（SC）WAT，并发现了对寒冷和季节上上调UCP1和其他线粒体基因的考虑能力，我们已经证明了这种现象具有人类培养中的人类脂肪细胞。 WAT的季节性变化特别令人感兴趣，因为这表明对寒冷天气有生理反应，而没有挑衅和无生理的实验条件。此外，我们发现肥胖的人类具有高sc的巨噬细胞燃烧也不会更新SC WAT UCP1，这表明脂肪注射会抑制WAT的热能能力增加。此过程中涉及许多免疫介入功能。基于这些数据，我们提出以下假设。假设1。反复暴露于寒冷的温度将扩大人类皮下的变化。这些效果是敏锐的，响应季节，并涉及免疫介质的激活。假设2。SC WAT的升级涉及脂肪组织免疫介质的急性增加，这可能是激活蛋白激酶A（PKA）的儿茶酚胺的来源。该过程在体内抑制了β受体阻滞剂。假设3。肥胖的胰岛素抵抗受试者对促炎的环境抑制了局部介体的抗性诱导的WAT变化具有抵抗力。假设4。冷和季节引起的SC WAT变化将导致组织的功能变化，其特征是线粒体解偶联增加，TG转换增加（脂解）和静息代谢率提高。 公共卫生：肥胖与胰岛素抵抗，糖尿病和心脏病紧密相关。最近的研究集中在人类中的棕色脂肪组织上，这可能会增加能量消耗并有助于预防肥胖症。该建议检查皮下白脂肪会在多大程度上变成棕色或米色。我们将确定该过程是否受到肥胖/代谢综合征的炎症状态的抑制，我们将表征冷对脂肪甘油三酸酯更新的影响。