Beraprost sodium, a stable prostacyclin analogue, improves insulin resistance in high-fat diet-induced obese mice
Beraprost sodium, a stable prostacyclin analogue, improves insulin resistance in high-fat diet-induced obese mice
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DOI：
10.1530/joe-12-0014
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发表时间：
2012-06-01
影响因子：
4
通讯作者：
Sunagawa, Kenji
中科院分区：
文献类型：
--
作者：
Inoue, Eriko;Ichiki, Toshihiro;Sunagawa, Kenji
肥胖诱导脂肪细胞肥大，导致促炎细胞因子如肿瘤坏死因子-α（TNF-α）和单核细胞趋化蛋白1（MCP 1（CCL 2））的产生。这些细胞因子在胰岛素抵抗的发展中起重要作用。据报道，贝前列素钠（BPS）是一种前列腺素I-2类似物，可减轻炎症。在这项研究中，我们研究了BPS对高脂饮食（HFD）小鼠葡萄糖代谢的影响。给4周龄的C57/B6雄性小鼠喂食HFD 12周（HFD组），治疗组在同一时期接受口服BPS（300 μ g/kg/天）。然后，检查了白色脂肪组织（WAT）的葡萄糖代谢、组织学变化和基因表达。HFD组体重增加，葡萄糖耐受不良和胰岛素抵抗。BPS治疗改善了葡萄糖耐量和胰岛素作用，而体重没有变化。WAT的组织学分析显示HFD组中脂肪细胞和巨噬细胞浸润的大小增加，这被BPS处理减弱。BPS减少HFD诱导的WAT中MCP 1和TNF-α的表达。BPS还减弱了HFD诱导的肝脂肪变性。这些结果表明BPS可能通过抑制WAT中的炎性细胞因子来改善葡萄糖耐受不良。BPS可能有利于治疗肥胖相关的葡萄糖耐受不良。内分泌学杂志（2012）213，285-291
Obesity induces hypertrophy of adipocyte resulting in production of pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF-alpha) and monocyte chemoattractant protein 1 (MCP1 (CCL2)). These cytokines play an important role in the development of insulin resistance. Beraprost sodium (BPS), a prostaglandin I-2 analogue, is reported to attenuate inflammation. In this study, we examined the effect of BPS on glucose metabolism in mice fed a high-fat diet (HFD). Four-week-old C57/B6 male mice were fed a HFD for 12 weeks (HFD group) and the treatment group received oral BPS (300 mu g/kg per day) for the same period. Then, glucose metabolism, histological changes, and gene expression of white adipose tissue (WAT) were examined. Body weight was increased, and glucose intolerance and insulin resistance were developed in the HFD group. Treatment with BPS improved glucose tolerance and insulin action without body weight change. Histological analysis of WAT showed an increase in the size of adipocyte and macrophage infiltration in the HFD group, which was attenuated by BPS treatment. BPS reduced HFD-induced expression of MCP1 and TNF-alpha in WAT. BPS also attenuated hepatic steatosis induced by the HFD. These results suggest that BPS improved glucose intolerance possibly through suppression of inflammatory cytokines in WAT. BPS may be beneficial for the treatment of obesity-associated glucose intolerance. Journal of Endocrinology (2012) 213, 285-291