Effect of troglitazone on plasma lipid metabolism and lipoprotein lipase
J Kobayashi, I Nagashima, M Hikita… - British journal of …, 1999 - Wiley Online Library
J Kobayashi, I Nagashima, M Hikita, H Bujo, K Takahashi, M Otabe, N Morisaki, Y Saito
British journal of clinical pharmacology, 1999•Wiley Online LibraryAims To clarify how troglitazone, an insulin‐sensitizing agent, affects lipid 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/m2) were
recruited for this study. 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 with troglitazone 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/m2) were
recruited for this study. 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 with troglitazone and …
Aims To clarify how troglitazone, an insulin‐sensitizing agent, affects lipid 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/m2 ) were recruited for this study. 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 with troglitazone and LPL enzyme protein mass in the culture media was measured by an enzyme linked immunosorbent assay. A reverse transcription polymerase chain reaction (RT‐PCR) using primers specific for the carboxyl terminal 135 amino acid of mouse LPL cDNA was used to evaluate the effect of troglitazone on expression of LPL and Northern blot analysis carried out to determine expression of LPL.
Results The average levels before treatment of fasting serum total cholesterol, triglycerides, high density lipoprotein cholesterol, plasma glucose and glycohaemoglobin A1c 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 levels 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 plasma 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 presence of 10, 20 or 30 μm of this compound increased in a dose dependent manner. 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 μm 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 the presence of 10 μm troglitazone.
Conclusions Troglitazone improves plasma triglyceride‐rich lipoproteins metabolism by enhancing the expression of LPL in adipocytes.
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