Cold Induced Changed in Human Subcutaneous White Adipose

描述（申请人提供）：最近通过PET-CT重新发现人类棕色脂肪组织，引发了更多关于产热和防御防御肥胖的研究。许多研究表明，小鼠的白色脂肪组织（WAT）有能力上调其产热能力，并成为“米色”。除了我们最近的研究外，没有研究表明典型的人类WAT仓库会变褐。我们最近检查了人类皮下（SC） WAT，发现UCP1和其他线粒体基因在应对寒冷和季节时具有相当大的上调能力，我们已经在培养的人类脂肪细胞中证明了这一现象。WAT的季节变化特别令人感兴趣，因为这表明了对较冷天气的生理反应，而没有挑衅性和非生理性的实验条件。此外，我们发现高SC WAT巨噬细胞负荷的肥胖人群也不会上调SC WAT UCP1，这表明脂肪炎症抑制了WAT增加的产热能力。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。反复暴露在低温下会放大人体皮下WAT的变化。随着季节的变化，这些变暖的影响会非常明显，并且涉及到免疫介质的激活。假设2。SC WAT的发病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。这一过程在体内被β受体阻滞剂抑制。假设3。肥胖胰岛素抵抗者对寒冷引起的WAT变化有抵抗性，这是由于促炎环境抑制了北京的局部介质。假设4。寒冷和季节引起的SC WAT变化将导致组织功能变化，其特征是线粒体解偶联增加，TG转换（脂肪分解）增加，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.