EFFECTS OF HEPARIN AND LOW-MOLECULAR-WEIGHT HEPARIN ON LIPID TRANSPORT DURING PARENTERAL-FEEDING IN THE RAT

Background: Treatment with heparin has been reported to interfere with lipid metabolism by release of Lipoprotein Lipase (LPL) into the circ ulation. The purpose of the present study was to determine the effects on LPL activity by anticoagulants in combination with total parentera l nutrition (TPN) in the rat. In an earlier investigation we could sho w that TPN, per se, caused a three-fold increase of triglyceride conte nt in liver tissue, retention of lipids in the circulation and disturb ed cholesterol metabolism with accumulation of cholesterol in the non High Density Lipoprotein (HDL) fraction of lipoproteins. The activity of Hepatic Lipase (HL) was decreased, while the activities of LPL in a dipose tissue and heart were up-regulated. Methods: Effects on lipid m etabolism by TPN for seven days with or without simultaneous administr ation of heparin or Low Molecular Weight Heparin (LMWH) were studied i n 52 healthy male Sprague-Dawley rats. Combinations of Heparin or LMWH and discontinuous or continuous administration of TPN solutions (incl uding approximately 8g triglycerides/kg body weight daily) were invest igated. Results: Addition of LMWH, but not heparin, to treatment with TPN resulted in significant up-regulation of LPL activity in the heart . Combination of heparin and continuous administration of TPN solution s was followed by modest, but significant, increases of S-Triglyceride s and HDL-Triglycerides. No differences between the mN groups were obs erved concerning liver steatosis, cholesterol metabolism, phospholipid metabolism or HL activity. Conclusion: Treatment with LMWH during mN resulted in upregulated LPL activity in the heart, which might represe nt a compensatory mechanism for enzyme release from the capillary wall s induced by anticoagulants. Administration of heparin, a more effecti ve lipase-releasing agent, was not associated with increased LPL activ ity. Heparin treatment in combination with continuous TPN administrati on was followed by increased levels of triglycerides in blood and HDL particles, suggesting that treatment with heparin might have impaired the capacity for LPL up-regulation, resulting in the development of hy perlipidemia. Further investigations are necessary for evaluation of t he mechanisms. Depletion of LPL activity could not be demonstrated by this study in healthy rats.