title: Low molecular weight heparin-induced increase in chylomicron-remnants clearance, is associated with decreased plasma TNF-α level and increased hepatic lipase activity.
abstract: OBJECTIVE
  The acute effect of heparin on lipoprotein clearance is well characterized. Yet, the effect of prolonged low-molecular-weight-heparin (LMWH) administration on post-prandial lipemia has remained so far unexplored. Recent reports suggest that LMWH could modify lipid and carbohydrate metabolism by diminishing TNFα-mediated inflammatory response. This, together with the known negative effect of TNF-α on insulin sensitivity, prompted us to hypothesize that LMWH would favorably affect post-prandial lipoprotein disposal.
  
  
  METHODS
  Twenty four patients were given a vitamin A-fat loading meal at the end of 6-week enoxaparin treatment and after 3-month washout period. Post-prandial lipemia was assessed by measuring retinyl-palmitate (RP) during 8hours following the meal. Insulin sensitivity index (ISI), plasma lipolytic activity and plasma TNF-α were measured.
  
  
  RESULTS
  Enoxaparin did not impact fasting plasma lipids and lipoproteins levels. Enoxaparin increased RP clearance in the chylomicron remnant (CMR) fraction by 32% (P<0.01). Additionally, enoxaparin decreased plasma TNF-α by 22% (P<0.01), increased hepatic lipase (HL) activity by 81% (P<0.01), along with a 2-fold increase in ISI (P<0.01). The decrease in CMR correlated with the reduction in TNFα and the increase in ISI and HL activity (R=0.48, -0.68, -0.56, respectively, p<0.05). Significant correlations were also found between the reduction in TNFα and both the increase in ISI and increase in HL activity (R=-0.43, -0.54, respectively, P<0.05).
  
  
  CONCLUSIONS
  The association of the effect on post-prandial metabolism, plasma TNFα level and HL activity during prolonged enoxaparin treatment may support the hypothesis that the beneficial outcome of enoxaparin may possibly be linked to anti-inflammatory and lipase-potentiating impact.
authors: The Bert Strassburger Lipid Center, Sheba Medical Center, Tel Hashomer, Israel; Department of Medicine, Tel Aviv-Sourasky Medical Center, Tel Aviv, Israel. Electronic address: itamar.grosskopf@sheba.health.gov.il.
authors: Itamar
authors: I
authors: Grosskopf
authors: The Bert Strassburger Lipid Center, Sheba Medical Center, Tel Hashomer, Israel.
authors: Aviv
authors: A
authors: Shaish
authors: The Bert Strassburger Lipid Center, Sheba Medical Center, Tel Hashomer, Israel; Department of Medicine, Tel Aviv-Sourasky Medical Center, Tel Aviv, Israel.
authors: Assaf
authors: A
authors: Ray
authors: The Bert Strassburger Lipid Center, Sheba Medical Center, Tel Hashomer, Israel; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors: Dror
authors: D
authors: Harats
authors: The Bert Strassburger Lipid Center, Sheba Medical Center, Tel Hashomer, Israel; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors: Yehuda
authors: Y
authors: Kamari
mesh_terms: D002914:Chylomicrons / Q000378:metabolism*; D005260:Female; D006495:Heparin, Low-Molecular-Weight / Q000494:pharmacology*; D006801:Humans; D008049:Lipase / Q000378:metabolism*; D008099:Liver / Q000187:drug effects* / Q000201:enzymology*; D008297:Male; D008875:Middle Aged; D019518:Postprandial Period; D014409:Tumor Necrosis Factor-alpha / Q000097:blood*
chemical_list: D002914:Chylomicrons; D006495:Heparin, Low-Molecular-Weight; D014409:Tumor Necrosis Factor-alpha; D008049:Lipase
keywords: Inflammation; Insulin sensitivity; Post-prandial lipemia