Department of Obstetrics and Gynecology, The University of Texas Medical Branch, Galveston, TX, USA.
Am J Obstet Gynecol. 2013 Apr;208(4):308.e1-7. doi: 10.1016/j.ajog.2013.01.013. Epub 2013 Jan 10.
Pioglitazone (PIO), an antidiabetic drug of the thiazolidinedione family, improves glucose and lipid metabolism in muscle, adipose, and liver tissues via peroxisome proliferator-activated receptor gamma activation. We hypothesize that PIO therapy will improve the metabolic status of offspring exposed to maternal obesity in a mouse model developmentally programmed for metabolic syndrome.
CD-1 female mice were fed a high-fat diet for 3 months prior to breeding and throughout pregnancy and lactation. The pups were weaned to a standard-fat diet. Offspring were randomly assigned to receive 40 mg/kg of PIO in 0.5% of methyl cellulose or 0.5% methyl cellulose by daily oral gavage for 2 weeks. The pre- and posttreatment total body weights of the pups were recorded. Visceral and subcutaneous adipose tissue were evaluated using microcomputed tomography. Serum analytes were measured. After treatment, minimally invasive microendoscopic fluorescence confocal imaging and intraperitoneal glucose tolerance tests were performed. The data were analyzed using appropriate statistical tests (significance, P < .05).
PIO therapy resulted in lower total body weight and lower visceral adipose tissue gain and increased subcutaneous adipose tissue. PIO significantly lowered triglycerides, insulin levels, and homeostasis model assessment of insulin resistance in males and fasting glucose in females. There was a trend toward larger adipocyte size.
Short-term PIO therapy in the offspring of obese mothers attenuates metabolic changes associated with the developmental programming of metabolic syndrome. These novel data suggest a potential role for drugs that activate peroxisome proliferator-activated receptor gamma receptors to prevent metabolic syndrome in the adult offspring at risk to develop metabolic alterations.
吡格列酮（PIO）是噻唑烷二酮类抗糖尿病药物，通过激活过氧化物酶体增殖物激活受体γ（PPARγ）改善肌肉、脂肪和肝脏组织中的葡萄糖和脂质代谢。我们假设 PIO 治疗将改善在发育过程中被编程为代谢综合征的肥胖母亲后代的代谢状态。
CD-1 雌性小鼠在繁殖前 3 个月以及整个妊娠和哺乳期均喂食高脂肪饮食。幼鼠断奶后给予标准脂肪饮食。后代随机分为两组，每天通过口服灌胃接受 40mg/kg 的 PIO 或 0.5%甲基纤维素，持续 2 周。记录幼鼠治疗前后的总体重。使用微计算机断层扫描评估内脏和皮下脂肪组织。测量血清分析物。治疗后，进行微创显微镜荧光共聚焦成像和腹腔内葡萄糖耐量试验。使用适当的统计检验（显著性，P <.05）分析数据。
PIO 治疗导致幼鼠总体重降低，内脏脂肪组织增加减少，皮下脂肪组织增加。PIO 显著降低了雄性的甘油三酯、胰岛素水平和胰岛素抵抗稳态模型评估，以及雌性的空腹血糖。脂肪细胞大小有增大的趋势。
肥胖母亲后代的短期 PIO 治疗可减轻与代谢综合征发育编程相关的代谢变化。这些新数据表明，激活过氧化物酶体增殖物激活受体γ受体的药物可能在有代谢改变风险的成年后代中发挥作用，以预防代谢综合征。
