beraprost and Obesity

Obesity induces hypertrophy of adipocyte resulting in production of pro-inflammatory cytokines such as tumor necrosis factor-α (TNF-α) and monocyte chemoattractant protein 1 (MCP1 (CCL2)). These cytokines play an important role in the development of insulin resistance. Beraprost sodium (BPS), a prostaglandin I2 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 μg/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-α 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.

Topics: Adipocytes; Adipose Tissue, White; Animals; Blood Glucose; Blood Pressure; Cell Size; Chemokine CCL2; Diet, High-Fat; Enzyme-Linked Immunosorbent Assay; Epididymis; Epoprostenol; Gene Expression; Glucose Intolerance; Heart Rate; Insulin; Insulin Resistance; Male; Mice; Mice, Inbred C57BL; Obesity; Reverse Transcriptase Polymerase Chain Reaction; Tumor Necrosis Factor-alpha; Vasodilator Agents

The prostacyclin analog, beraprost sodium (BPS), was examined for its potential to improve the symptoms of obesity-type diabetes (i.e., hyperglycemia, hyperinsulinemia, dyslipidemia, histopathologic changes, and diabetic complications).. Obese Zucker rats, an experimental model of genetic obesity-induced type 2 diabetes, were repeatedly administered BPS at oral doses of 0.2 or 0.6 mg x kg(-1) x day(-1) b.i.d. for 12 weeks, and serum chemistry, urinalysis, and histopathologic examination were performed.. BPS dose-dependently suppressed serum glucose, insulin, triglyceride, and cholesterol levels in obese animals. In oral glucose tolerance test, BPS suppressed the post-glucose-loading elevation of serum glucose in a dose-dependent manner. Urinary N-acetyl-beta-D-glucosaminidase was significantly lower in BPS-treated obese animals compared with control animals, although no significant differences were observed in urinary protein levels between the BPS-treated groups and the control group. In addition, histopathologic examination revealed significant protective effects of BPS against renal disorder in obese animals. Histopathologically, BPS also inhibited the progression of hepatic steatosis, hypertrophy of adipose tissue, and pancreatic fibrosis. Furthermore, thermographic analysis of the hind limb sole skin surface indicated a significant increase in temperature in BPS-treated animals, compared with control animals, which was likely due to improved blood circulation by administration of BPS.. BPS suppressed the pathogenesis and development of diabetes and its complication, nephropathy, which was presumably accompanied by improving glucose intolerance and insulin resistance in obese Zucker rats.

Topics: Adipose Tissue; Animals; Blood Glucose; Blood Pressure; Body Weight; Cholesterol; Cryoprotective Agents; Epoprostenol; Glycated Hemoglobin; Insulin; Kidney; Liver; Male; Metabolic Syndrome; Obesity; Pancreas; Rats; Rats, Zucker; Skin Temperature; Triglycerides