Effects of Tiadenol and Clofibrate on Plasma Post Heparin Lipolytic Hepatic, Extrahepatic and Monoglyceride Hydrolase Activities in Rats with Hypertriglyceridemia Induced by a Sucrose Rich Diet

Summary

Normal rats fed an isocaloric sucrose-rich diet (SRD) for 3 weeks developed high levels of triacylglycerol in plasma (P) (mmol triacylglycerol I^-1) heart (H) and liver (L) tissues (μmol triacylglycerol mg DNA^-1) as compared to control rats fed the standard chow (STD) (X±SEM; P: SRD 1.32±0.06 vs STD 0.49±0.05, P < 0.001; H: SRD 2.1±0.17 vs STD 0.94±0.01, P < 0.001; L: SRD 8.48±1.47 vs STD 1.71±0.12, P < 0.001). A simultaneous drop in the activities (μmol glycerol ml^-1 hr^-1) of several plasma post heparin lipolytic enzymes was observed; total triglyceride lipase (T-TGL): SRD 5.32±0.34 vs STD 7.48±0.64, P < 0.01; lipoprotein lipase (LPL): SRD 1.61±0.26 vs STD 2.42±0.41, P < 0.05; hepatictriglyceride lipase (H-TGL): SRD 3.71±0.28 vs STD 5.05±0.69, P < 0.05 and monoglyceride hydrolase (MGH) (μmol glycerol I^-1 min^-1): SRD 558±108 vs STD 1165±45, P < 0.001. Rats fed the SRD presented glucose intolerance after i.v. glucose (Kg × 10^-2; 1.06±0.09 vs 2.61±0.14 of STD, P < 0.001) in spite of the presence of hyperinsulinism (Σ plasma IRI μU/ml from 0 to 30 min: 184.6±23.6 vs 100.5±9.7 of STD, P < 0.01) suggesting that a state of insulin resistance had developed.

The addition of 0.25 g% of either tiadenol (TIAD) or clofibrate (CLOF) to the sucrose-rich diet during the 3rd. week of the experimental period resulted in a highly significant fall of plasma and tissue triacylglycerol levels as compared to rats receiving the SRD alone; P: SRD + TIAD 0.73±0.04, SRD + CLOF 0.79±0.09, P < 0.001; H: SRD + TIAD 1.44 ±0.06, SRD ± CLOF 1.10±0.18, P < 0.001; L: SRD + TIAD 3.02±0.30, SRD + CLOF 3.35±0.48, P < 0.01. Animals receiving either hypolipemic drug showed stagnation of body weight gain associated with a lower food intake. Neither of these two intervening events were apparently responsible for the triglyceride lowering effects associated with the drug treatment, since a special control group of rats receiving a sucrose-rich diet quantitatively restricted so as to mimic the calories spontaneously eaten by the drug treated group, still exhibited H and L triacylglycerol levels comparable to those found in rats eating “ad libitum” the SRD alone.

Clofibrate and tiadenol treatment was also accompanied by a striking increase in all the plasma post heparin lipolytic enzymes measured; T-TGL: SRD + CLOF 7.80±0.42 P < 0.001; SRD / TIAD 6.39±0.16 P < 0.05; H-TGL: SRD + CLOF: 4.80±0.36; SRD + TIAD: 4.62±0.46, P < 0.05; LPL: SRD + CLOF 2.89±0.36, P < 0.01; SRD + TIAD 2.06±0.43; MGH: SRD + CLOF 928±102, SRD + TIAD 802±106, P < 0.05. Simultaneously, glucose tolerance and insulin responses to i.v. glucose were both normalized after tiadenol treatment (kg × 10^-2: 2.44±0.10 and Σ plasma IRI from 0 to 30 min: 84.8±6.1). Thus, under the present experimental design clofibrate or tiadenol were both able to reverse partially or completely the abnormal metabolic, enzymatic and hormonal parameters investigated by us in rats fed an isocaloric sucrose-rich diet.

Key-Words:

Sucrose-Rich Diet - Plasma Post Heparin Lipolytic Activities - Hipolypemic Drugs - Clofibrate - Tiadenol - Hypertriglyceridemia - Serum Lipids