Mirjam Hacquebard

Vitamin E: absorption, plasma transport and cell uptake

Purpose of reviewLarge-scale clinical trials have failed to demonstrate a benefit for vitamin E supplementation in cardiovascular prevention. This contrasts with previous epidemiological studies indicating that individuals with high vitamin E status benefit from protection against chronic illnesses, including cardiovascular diseases. These conflicting results suggest that the metabolism of supplemental versus naturally delivered vitamin E and their potential roles, other than a potent antioxidant action, are not fully understood. The purpose of this review is to provide an update on current knowledge on the intestinal absorption of vitamin E, its plasma transport and its supply to cells. The review will also discuss the intravascular metabolism of intravenously delivered vitamin E. Recent findingsAlthough the luminal digestion of vitamin E is fairly well understood, several pathways regulating net vitamin E absorption remain to be elucidated. In several cell types, cholesterol and vitamin E share common mechanisms for cellular uptake (scavenger receptor B type I and LDL receptors) and efflux (ABCA1 transporters). The role of specific binding proteins in α-tocopherol intracellular trafficking is increasingly being understood, leading to new insights into the non-antioxidant functions of vitamin E. SummarySubstantial progress has been made in characterizing the plasma transport of vitamin E and its delivery to cells. Mechanisms regulating the balance between the cellular uptake and efflux of vitamin E are under investigation. Vitamin E is not only an antioxidant but may also modulate pathways of cell signalling and gene expression. The translation of this new knowledge into clinical studies will help define future indications for vitamin E supplementation. Abbreviations ABC: adenosine triphosphate-binding cassette; α-TTP: α-tocopherol transfer protein; LPL: lipoprotein lipase; PLTP: phospholipid transfer protein; SR-BI: scavenger receptor B type I; TAP: tocopherol-associated protein; TBP: tocopherol-binding protein.

Rapid cellular enrichment of eicosapentaenoate after a single intravenous injection of a novel medium-chain triacylglycerol:fish-oil emulsion in humans

BACKGROUND Dietary deficiency in n-3 (omega-3) polyunsaturated fatty acids (PUFAs) prevails in Western populations and potentially results in adverse health outcomes. To circumvent the slow n-3 PUFA incorporation in phospholipids of key cells after oral supplementation, a new preparation for intravenous bolus injection was developed with 20 g triacylglycerols/100 mL of a mixture of 80% medium-chain triacylglycerols (MCTs) and 20% fish oil (FO) (wt:wt), and 0.4 g alpha-tocopherol/100 mL of the same mixture. OBJECTIVE Our objective was to document the enrichment of n-3 PUFAs in leukocyte and platelet phospholipids after a bolus intravenous injection of MCT:FO in men. DESIGN Twelve healthy male subjects received injections over a 5-min period of 50 mL of either MCT:FO or a control MCT:long-chain triacylglycerol (MCT:LCT) emulsion containing 20 g triacylglycerols/100 mL with equal amounts (wt:wt) of MCT and soybean triacylglycerols (LCT) and containing 0.02 g alpha-tocopherol/100 mL; after an 8-wk interval, the subjects received injections of the other preparation. RESULTS Clinical and biological variables that assessed tolerance and safety remained unchanged. Plasma elimination was faster for MCT:FO than for MCT:LCT (half-life: 24.5 +/- 3.5 min compared with 32.9 +/- 3.0 min; P < 0.025). This was associated with a greater increase in the plasma nonesterified fatty acid concentration. The content of n-3 PUFAs, specifically eicosapentaenoic acid (20:5n-3), increased in leukocyte and platelet phospholipids within 60 min and > or =24 h after MCT:FO injection. CONCLUSION Bolus intravenous injection of a novel MCT:FO emulsion allows rapid enrichment of cells with n-3 PUFAs.

Oxidative stress produced by circulating microparticles in on-pump but not in off-pump coronary surgery.

Objective — This study was undertaken to assess whether plasmas isolated during off-pump coronary surgery trigger less oxidative stress than those isolated during on-pump surgery. Methods and results — Plasmas were sampled from patients before (T0), just after (T1) and 24 hours after (T2) cardiac surgery (n = 24 on-pump and n = 10 off-pump). Rings of rat thoracic aortas were incubated for 20 hours with these different plasmas (100 μl + 4 ml medium) or saline (control). Thereafter, superoxide anion production was assessed by chemiluminescence and the mean signal was expressed as percent of that in the control ring. In rat aorta exposed to plasmas from on-pump CABG patients (n = 6), the signal was enhanced by 210 ± 29% at T1 (P < 0.05) and by 174 ± 29% at T2 (P < 0.05) versus 53 ± 12% at T0. Moreover, at T1 and T2, there was an upregulation of p22phox , the key subunit of NADPH oxidase, the main enzyme involved in oxidative stress of the vascular wall. In contrast, off-pump plasmas did not induce this superoxide production. Incubation with microparticles obtained by ultracentrifugation also markedly enhanced the signal at T1 and T2 (vs. T0) in the on-pump group (but not in the off-pump group). Selective removal of CD34, CD105, CD59, CD146, CD42 microparticles using flow cytometry did not abolish the signal. CRP and SAA plasma levels were enhanced only at T2 in both groups. Conclusions — Plasmas isolated after on-pump but not off-pump coronary bypass surgery can induce superoxide generation by the vascular wall which seems related to circulating microparticles remaining present at least 24 hours after the procedure that might be of endothelial origin.

Tocopherol in lipoproteins and blood cells after cardiac surgery.

Abstract: Cardiac surgery was associated with a marked reduction in circulating LDL and HDL particles, which in turn largely affectd α‐toc transport. α‐toc was decreased in WBCs but not in PLTs and RBCs. An increased hydroperoxide content was observed in LDL and possibly in HDL after cardiac surgery.

The Metabolic Syndrome of ω3-Depleted Rats. X: Comprehensive View

The present report complements recent publications on the occurrence of a metabolic syndrome in rats deprived of a dietary supply of long-chain polyunsaturated � 3 fatty acids and on the attempt to correct the resulting metabolic and hormonal defects by exposure of the � 3-depleted rats to a diet enriched with flaxseed oil rich in � -linolenic acid (C18:3� 3). Emphasis is placed (i) on the much slower time course for the depletion in docosahexaenoic acid (C22:6� 3) and accumulation of docosapentaenoic acid (C22:5� 6) and their reversal during dietary deprivation and replenishment of � 3 fatty acids in brain phospholipids, as opposed to liver or intestinal phospholipids, (ii) on the role of circulating phos- pholipids in the transfer of C22:6� 3, synthesized from C18:3� 3 in hepatocytes, from the liver to the brain in the rats de- prived of a dietary supply of � 3 fatty acids, and (iii) on the unfavorable effect of an increase in the total lipid content of the diet from 5 to 10% (w/w) in the perspective of the correction of liver steatosis and visceral obesity in the � 3-depleted rats.

Erratum: Effect of ALA-enriched food supply on cardiovascular risk factors in males (Lipids DOI: 10.1007/s11745-009-3307-5)

The first sentence of the last paragraph of the manuscript contains a mistake. ‘‘In summary, providing ALA through a variety of fortified foods enables to considerably increase the n-6/n-3 ratio in the diet without changing the subject’s dietary habits.’’ must be replaced by ‘‘In summary, providing ALA through a variety of fortified foods enables to considerably decrease the n-6/n-3 ratio in the diet without changing the subject’s dietary habits’’.

The Metabolic Syndrome of ω3-Depleted Rats. VIII. Dietary Lipid- Induced Liver Steatosis~!2009-08-18~!2009-11-13~!2010-06-11~!

The present study aims at investigating the determinants of the undesirable aggravation of liver steatosis observed in rats first deprived, for 7 months from the 6 th week after birth onwards, of a dietary supply of long-chain polyunsaturated 3 fatty acids by exposure to a 5% sunflower oil-containing diet and then given access for about 2 weeks to the same diet enriched with 5% flaxseed oil in order to restore a sufficient 3 fatty acid content of tissue lipids. Control rats were exposed for 7 months to a 5% soybean oil-containing diet and then given access for about 2 weeks to the same diet enriched with either 5% flaxseed oil or another 5% soybean oil. In all cases, the increase in the lipid content of the diet provoked an increase in liver triglyceride content. The ratio between the daily increment in the C18:3 3 content of liver triglycerides caused by the switch in diet and the C18:3 3 relative content of the diet used after the switch averaged 0.035 in the control rats eventually exposed to the soybean-enriched diet, 0.051 in the control rats eventually exposed to the flaxseed oil-enriched diet and 0.120 in the 3-deficient rats eventually also exposed to a flaxseed oil-enriched diet. Thus, under the present experimental conditions, the induction or aggravation of liver steatosis, and possibly also the parallel increase in adipose tissue mass, may correspond to the deposition of dietary lipids, also involving an increase in food intake, more pronounced in the 3-depleted rats than in the control animals.