Female Mice Lacking p47phox Have Altered Adipose Tissue Gene Expression and are Protected against High Fat-Induced Obesity and Metabolic Syndrome

Oxidative stress in adipose tissue and liver has been linked to the development of obesity. NADPH oxidases (NOX) enzymes are a major source of reactive oxygen species (ROS). The current study was designed to determine if NOX2-generated ROS play a role in development of obesity and metabolic syndrome after high fat feeding. Wild type (WT) mice and mice lacking the cytosolic NOX2 activated protein p47phox (P47KO) were fed AIN-93G diets or high fat diets (HFD) containing 45% fat and 0.5% cholesterol for 13 weeks from weaning. Affymetrix array analysis revealed dramatically less expression of mRNA of genes linked to energy metabolism, adipocyte differentiation (PPARgamma, Runx2) and fatty acid uptake (CD36, lipoprotein lipase) in fat pads from female HFD-P47KO mice compared to HFD-WT females. These data suggest that NOX2 is an important regulator of metabolic homeostasis and that NOX2-associated ROS plays an important role in development of diet-induced obesity particularly in the female fat pads from p47phox and wild type fed a high fat or control diet脂肪组织与肝脏的氧化应激已被证实与肥胖的发生发展密切相关。烟酰胺腺嘌呤二核苷酸磷酸氧化酶（NADPH oxidases, NOX）是活性氧（reactive oxygen species, ROS）的主要产生来源。本研究旨在探究NADPH氧化酶2（NOX2）介导产生的活性氧是否在高脂喂养后肥胖及代谢综合征的发生发展中发挥作用。将野生型（Wild type, WT）小鼠与胞质NOX2激活蛋白p47phox敲除（P47KO）小鼠分为两组，分别饲喂AIN-93G基础饲料或含45%脂肪、0.5%胆固醇的高脂饲料（high fat diets, HFD），自断奶起持续喂养13周。Affymetrix基因芯片（Affymetrix array）分析结果显示，相较于高脂喂养的野生型雌性小鼠，高脂喂养的P47KO雌性小鼠脂肪垫中，与能量代谢、脂肪细胞分化（过氧化物酶体增殖物激活受体γ（PPARγ）、Runt相关转录因子2（Runx2））及脂肪酸摄取（CD36、脂蛋白脂酶（lipoprotein lipase））相关的基因mRNA表达水平显著降低。上述研究数据表明，NOX2是代谢稳态的重要调控因子，且NOX2相关活性氧在饮食诱导肥胖的发生发展中发挥关键作用，尤其在高脂或对照饲料喂养的p47phox敲除及野生型雌性小鼠的脂肪组织中。