年龄的增长容易引起老年性肥胖。老年性肥胖与胰岛素抵抗、脂肪肝、高血压和动脉粥样硬化等代谢性疾病相关。目前认为脂肪褐色化降低是导致老年性肥胖的重要原因，但机制仍不清楚。我们发现老年小鼠褐脂化降低，前列腺素PGE2受体EP3在老年小鼠巨噬细胞中表达降低；低温诱导后，巨噬细胞EP3特异敲除小鼠褐脂化程度降低，p38磷酸化降低，儿茶酚胺及酪氨酸羟化酶水平降低。推测巨噬细胞EP3通过p38调控酪氨酸羟化酶活性和儿茶酚胺合成与分泌，进而调控老年性肥胖和褐脂化。我们将利用药物学手段和遗传学手段，研究EP3在巨噬细胞介导老年性肥胖中褐脂化的作用；儿茶酚胺是否介导巨噬细胞EP3在老年性肥胖和褐脂化；p38是否介导了巨噬细胞EP3参与的老年性肥胖中褐脂化过程中儿茶酚胺合成；何种G蛋白介导巨噬细胞EP3参与的老年性肥胖中褐脂化过程。明确EP3调控巨噬细胞参与的老年性肥胖和褐脂化的机制，预防衰老引起的肥胖。

Aging causes obesity, which is always associated with metabolic diseases, such as insulin resistance, fatty liver, high blood pressure and atherosclerosis. The decrease of adipose browning plays important roles in the growing of adipose mass, but the mechanism is still unclear. The browning of adipocytes and the expression of E-prostanoid 3 receptor decreased during aging. The absence of EP3 in macrophages inhibited the browning of adipocytes, decreased the phosphorylation of p38 and the level of tyrosinekinase and catecholamine.Thus, EP3 in macrophages may modulate the adipose browning and obesity during aging through p38/tyrosinekinase/catecholamine pathway. We will investigate the role of EP3 in macrophages mediating the browning of adipocytes during aging, the role of p38 phosphorylation to modulate catecholamine secretion in brown adipose tissue, and the identify of the G protein that mediates activation of p38. This study will provide an opportunity to study the molecular mechanisms that EP3 in macrophages stimulates adipose browning during aging and prevents aging induced-obesity.