Carpentier 10_11

This study deals with the sustained enrichment of liver phospholipids and triglycerides in long-chain polyunsaturated ˆ3 fatty acids (ˆ3) found after the bolus intravenous injection of a novel medium-chain triglyceride:fish oil emulsion (MCT:FO) to streptozotocin (Type 1) and GotoKakizaki (Type 2) diabetic rats. Twenty hours after injection of the MCT:FO emulsion, the relative concentration of ˆ3 was indeed higher in liver phospholipids and triglycerides than that found in rats injected with either saline or a control medium-chain triglyceride:long-chain triglyceride emulsion. This coincided with a decrease in the ponderal percentage of C18:3ˆ3, C20:4ˆ6 and/or C22:4ˆ6 in liver triglycerides. The present study further documents differences between streptozotocin-induced and Goto-Kakizaki diabetic rats in terms of body weight, glycemia, liver triglyceride content and the fatty acid pattern of both liver phospholipids and triglycerides, as well as a close correlation in the latter animals between liver and plasma phospholipids or triglycerides as far as the ratio in the relative concentration of selected fatty acids representative of desaturase and elongase activities is concerned. In light of these and previous findings, it is proposed that the beneficial metabolic and functional events of the MCT:FO emulsion may display not solely a rapid but also sustained time course. Introduction It was recently reported [Portois L, et al, Nutr Clin Metab 18 (Suppl 1): abs. S53, 2004] that the bolus intravenous injection of a medium-chain triglyceride:fish oil emulsion (MCT:FO) to normal human subjects increases within 60 min the content of leucocyte and platelet phospholipids in long-chain polyunsaturated ˆ3 fatty acids (C20:5ˆ3 and C22:6ˆ3). This procedure was proposed, therefore, as a new approach to restore rapidly a sufficient phospholipid content of these ˆ3 fatty acids in selected subjects, such as those susceptible to undergo cardiac arrhythmia in response to anesthesia and surgery. Likewise, it was documented that, in both ˆ3-depleted rats (second generation) and normal animals examined 60 min after the bolus injection of the MCT:FO emulsion, a sizeable increase of the phospholipid content in ˆ3 fatty acids was observed in the liver, as distinct from circulating cells in direct contact with the injected lipids, this coinciding with a decrease of the hepatic triglyceride content in the ˆ3-depleted rats [Portois L, et al, Eur J Physiol: abs. (In press)]. In the present study, comparable experiments were conducted in animal models of either Type 1 or Type 2 diabetes, namely in rats rendered diabetic by a prior administration of streptozotocin (STZ rats) or Goto-Kakizaki rats with inherited non-insulin dependent diabetes (GK rats). The major aims of this study were to explore whether, in these diabetic rats, the injection of the MCT:FO emulsion would result in a sustained increase of the phospholipid content in ˆ3 fatty acids of the liver and concomitant changes in the hepatic triglyceride content and/or fatty acid composition. For the purpose of comparison other STZ and GK rats were injected with either saline or a MCT:LCT emulsion containing equal amounts (weight) of MCT lipids and soybean LCT lipids and currently used for parenteral nutrition (Medialipid®, B. Braun). Materials and methods The MCT:FO emulsion contained 20% (w:v) of a mixture of 80% medium-chain triacylglycerols and 20% fish oil. It also contained 2.5% (w:v) glycerol and 1.2% (w:v) egg-derived INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE 17: 643-647, 2006 643 Sustained enrichment of liver phospholipids and triglycerides in eicosapentaenoate after a bolus intravenous injection of a medium-chain triglycerides:fish oil emulsion to streptozotocin (Type 1) and Goto-Kakizaki (Type 2) diabetic rats YVON A. CARPENTIER, DAVID FONTAINE, ANNE OTTO, LAURENCE PORTOIS, JEANINE FONTAINE and WILLY J. MALAISSE Laboratories of Experimental Surgery and Physiology and Pharmacology, Brussels Free University, B-1070 Brussels, Belgium Received November 10, 2005; Accepted January 13, 2006 _________________________________________ Correspondence to: Professor Willy J. Malaisse, Laboratory of Experimental Surgery, Brussels Free University, 808 Route de Lennik, B-1070 Brussels, Belgium E-mail: [email protected]