Beraprost sodium, a stable prostacyclin analogue, improves insulin resistance in high-fat diet-induced obese mice.

Abstract

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.

• Authors: Eriko Inoue, Toshihiro Ichiki, Kotaro Takeda, Hirohide Matsuura, Toru Hashimoto, Jiro Ikeda, Aya Kamiharaguchi, Kenji Sunagawa
• Journal: The Journal of endocrinology (J Endocrinol) Vol. 213 Issue 3 Pg. 285-91 (Jun 2012) ISSN: 1479-6805 [Electronic] England
• PMID: 22460613 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Blood Glucose
• Ccl2 protein, mouse
• Chemokine CCL2
• Insulin
• Tumor Necrosis Factor-alpha
• Vasodilator Agents
• beraprost
• Epoprostenol

Topics

• Adipocytes (cytology, drug effects, metabolism)
• Adipose Tissue, White (cytology, drug effects, metabolism)
• Animals
• Blood Glucose (metabolism)
• Blood Pressure (drug effects)
• Cell Size (drug effects)
• Chemokine CCL2 (genetics, metabolism)
• Diet, High-Fat (adverse effects)
• Enzyme-Linked Immunosorbent Assay
• Epididymis (metabolism)
• Epoprostenol (analogs & derivatives, pharmacology)
• Gene Expression (drug effects)
• Glucose Intolerance (blood, physiopathology, prevention & control)
• Heart Rate (drug effects)
• Insulin (blood)
• Insulin Resistance
• Male
• Mice
• Mice, Inbred C57BL
• Obesity (blood, etiology, physiopathology)
• Reverse Transcriptase Polymerase Chain Reaction
• Tumor Necrosis Factor-alpha (genetics, metabolism)
• Vasodilator Agents (pharmacology)