Objective: To study the effect of pioglitazone on plasma homocysteine in insulin resistant rats induced by high-fat diet.

Methods: 24 Wistar rats were randomized into 3 groups: a control group (n = 8) was fed with normal feeds. High-fat diet was given to a high-fat group and a pioglitazone group. Pioglitazone (10 mg/kg) was then administered by gavage daily for 11 weeks to the pioglitazone group. At week 11, glucose tolerance test was performed, and serum insulin, fasting glucose and plasma homocysteine were detected. Visceral adipose was weighted and then the ratio of visceral adipose over body weight calculated.

Results: Fasting glucose, fasting insulin, insulin resistance index (HOMA IR), and the visceral adipose were significantly different among the 3 groups. Fasting glucose, fasting insulin, HOMA IR, and visceral adipose were all significantly lower in the pioglitazone group than those in the high fat group (P < 0.01). Plasma homocysteine decreased significantly in the pioglitazone-treated rats [(8.8 +/- 1.39) micromol/L] as compared with the other two groups [control group: (9.95 +/- 2.40) micromol/L and high fat group: (35.7 +/- 14.1) micromol/L]. Correlation analysis showed that fasting glucose, fasting insulin, HOMA IR and visceral adipose were all factors influencing the plasma homocysteine. Stepwise regression test showed only fasting glucose (r = 0.504, P = 0.031) and HOMA IR (r = 0.302, P = 0.046) independently affected the level of plasma homocysteine.

Conclusion: It is concluded that pioglitazone can lower plasma homocysteine in insulin resistant Wistar rats induced by high-fat diet.

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