Li Linzhao, Yang Guang, Liao Guangneng, Mei Jie, Li Lan, Wang Chengshi, Yuan Yujia, Shi Yujun, Liu Jingping, Zhong Zhihui, Cheng Jingqiu, Lu Yanrong, Clarke Iain J, Chen Younan
Key Laboratory of Transplant Engineering and Immunology, NHFPC; Regenerative Medicine Research Center, West China Hospital, Sichuan University, Chengdu, PR China.
Animal Center, West China Hospital, Sichuan University, Chengdu, PR China.
Steroids. 2017 Dec;128:105-113. doi: 10.1016/j.steroids.2017.09.005. Epub 2017 Oct 4.
Metabolic syndrome (MetS) is characterized by a cluster of key features, which include abdominal obesity, insulin resistance, hypertension, and dyslipidemia. The aim of this study was to assess the impact of elevated glucocorticoid levels on the development of MetS in middle-aged female rhesus monkeys (Macaca Mulatta) after ovariectomy. Six female ovariectomized rhesus monkeys (9-13years) were randomly assigned to either a control group (normal diet, n=3) or a group in which MetS was facilitated (n=3). The MetS group fed with HFD (15% fat) and received oral prednisone acetate treatment (50mg/day). After 24months, the GCs treatment was withdrawn with continuation of high-fat feeding for a further 12months. After 24months, the MetS group displayed a significant increase in body weight and abdominal circumference. Additionally, the MetS animals displayed abnormal serum lipids, insulin resistance and impaired glucose tolerance. Histology of liver biopsies indicated marked accumulation of lipid droplets in hepatocytes of MetS animals. Withdrawal of GCs treatment led to recovery from above-mentioned metabolic disorders. Whereas GCs treatment increased leptin expression, it lowered expression of adiponectin and other factors in adipose tissue. Expression of Hydroxy-steroid dehydrogenase-1 and glucose transporter type-4 in the livers of MetS animals were reduced. We conclude that in the context of high fat diet, high levels of exogenous GCs contribute to the development of MetS in non-human primates.
代谢综合征(MetS)的特征是一系列关键特征,包括腹部肥胖、胰岛素抵抗、高血压和血脂异常。本研究的目的是评估卵巢切除术后中年雌性恒河猴(猕猴)糖皮质激素水平升高对代谢综合征发展的影响。六只雌性去卵巢恒河猴(9 - 13岁)被随机分为对照组(正常饮食,n = 3)或促进代谢综合征发生的组(n = 3)。代谢综合征组喂食高脂饮食(15%脂肪)并接受口服醋酸泼尼松治疗(50mg/天)。24个月后,停止糖皮质激素治疗,继续高脂喂养12个月。24个月后,代谢综合征组体重和腹围显著增加。此外,代谢综合征动物出现血脂异常、胰岛素抵抗和糖耐量受损。肝脏活检组织学显示代谢综合征动物肝细胞中脂滴明显积累。停止糖皮质激素治疗导致上述代谢紊乱恢复。虽然糖皮质激素治疗增加了瘦素表达,但它降低了脂肪组织中脂联素和其他因子的表达。代谢综合征动物肝脏中羟基类固醇脱氢酶 - 1和葡萄糖转运蛋白4型的表达降低。我们得出结论,在高脂饮食的情况下,高水平的外源性糖皮质激素会导致非人类灵长类动物发生代谢综合征。