Effect of troglitazone on plasma lipid metabolism and lipoprotein lipase

Aims To clarify how troglitazone, an insulin-sensitizing agent, affects lip id metabolism and postheparin plasma lipoprotein lipase (LPL). Methods Fifteen patients (3 male, 12 female) (the average age 62+/-7 years; the mean body mass index (BMI) 25 +/- 3 kg/m(2)) were recruited for this s tudy. The serum lipids and postheparin plasma lipoprotein lipase (LPL) mass before and 4 weeks after oral administration of troglitazone (200 mg day(- 1)) were measured. A mouse preadipocyte cell line, 3T3-L1, was incubated wi th troglitazone and LPL enzyme protein mass in the culture media was measur ed by an enzyme linked immunosorbent assay. A reverse transcription polymer ase chain reaction (RT-PCR) using primers specific for the carboxyl termina l 135 amino acid of mouse LPL cDNA was used to evaluate the effect of trogl itazone on expression of LPL and Northern blot analysis carried out to dete rmine expression of LPL. Results The average levels before treatment of fasting serum total choleste rol, triglycerides, high density lipoprotein cholesterol, plasma glucose an d glycohaemoglobin Ale were 5.6+/-0.9, 1.8+/-1.0, 1.5+/-0.5, 8.1+/-1.7 mmol l(-1) and 7.8+/-1.6% respectively. Four weeks after treatment, those level s were 5.4+/-0.9, 1.2+/-0.3 (P= 0.004), 1.6+/-0.5 (P=0.02)mmol l(-1), 7.7+/ -2.3 mmol l(-1) and 7.3+/-0.6% (P= 0.01), respectively. The postheparin pla sma LPL mass increased from 226+/-39 to 257+/-68 ng ml(-1) (P=0.03) during that period. The LPL mass in the media of 3T3 L1 cells cultured in the pres ence of 10, 20 or 30 mu M Of this compound increased in a dose dependent ma nner. RT-PCR revealed that the area of the bands of the RT-PCR products on 1.5% agarose gel analyzed with NIH image from the cell extracts cultured in the presence of 10 mu M troglitazone was significantly larger (P= 0.0069) than that in the absence of this compound. Northern blot analysis revealed that in the cultured 3T3-L1 cells, the expression of LPL was enhanced in th e presence of 10 mu M troglitazone. Conclusions Troglitazone improves plasma triglyceride-rich lipoproteins met abolism by enhancing the expression of LPL in adipocytes.