Cold Induced Changed in Human Subcutaneous White Adipose

描述（由申请人提供）：最近通过PET-CT重新发现了人类棕色脂肪组织，启动了更多关于产热和肥胖防御的研究。许多研究表明，小鼠的白色脂肪组织（WAT）具有上调其产热能力并变成“米色”的能力。除了我们最近的研究外，没有研究表明典型的人类WAT仓库会发生布朗宁。我们最近研究了人类的皮下（SC）WAT，发现了相当大的能力，上调UCP 1和其他线粒体基因，以应对寒冷和季节，我们已经证明了这种现象与人类脂肪细胞培养。WAT的季节性变化特别令人感兴趣，因为这表明了对寒冷天气的生理反应，而没有刺激性和非生理性的实验条件。此外，我们发现具有高SC WAT巨噬细胞负荷的肥胖人也不上调SC WAT UCP 1，这表明脂肪炎症抑制了WAT产热能力的增加。许多免疫介导的功能参与了这一过程。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会放大人体皮下WAT beiging的变化。这些beiging效应被视为急性，在响应季节，并涉及免疫介质的激活。假设2. SC WAT的发生涉及脂肪组织免疫介质的急剧增加，这可能是激活蛋白激酶A（PKA）的儿茶酚胺的来源。这一过程在体内可被β受体阻滞剂抑制。假设3.肥胖胰岛素抵抗受试者对冷诱导的WAT变化具有抵抗性，这是由于促炎环境抑制了Beiging的局部介质。假设4.冷和季节诱导的SC WAT变化将导致组织的功能变化，其特征在于线粒体解偶联增加、TG周转增加（脂解）和静息代谢率增加。

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.