Effect of Vitamin D Treatment on Glucose Homeostasis and Metabolism in Lebanese Older Adults: A Randomized Controlled Trial.

BACKGROUND: A low serum 25-hydroxyvitamin D [(25(OH) D)] concentration was shown to correlate with higher fasting blood glucose (FBG) and insulin levels. Since age affect insulin sensitivity and the metabolism, we aimed in this randomized controlled trial to investigate the effect of vitamin D supplementation on glucose homeostasis and index of insulin resistance in elderly subjects living in Beirut, Lebanon. METHODS: Participants (n= 115) deficient in vitamin D were randomly divided into two groups, a group receiving 30,000 IU cholecalciferol/week for a period of 6 months, and a placebo group. The index of insulin resistance HOMA (homeostasis model assessment) was the primary outcome. Glucose homeostasis and metabolic markers were also measured at start of treatment and at 6 months. RESULTS: Vitamin D supplementation led to significant improvements in blood levels of [25(OH) D] (P< 0.0001), and a significant decreased of HOMA, PTH and FBG concentrations (P< 0.0001) in the intervention group compared to placebo. No significant changes were observed in HbA1c levels for both groups. Total cholesterol and LDL cholesterol concentrations have also decreased significantly in the intervention group (P< 0.0001). CONCLUSION: Short-term supplementation with cholecalciferol improved vitamin D status, and markers of insulin resistance in healthy elder population. This trial was registered at ClinicalTrials.gov; Identifier number#:NCT03478475.

Preservation of micronutrients during rapeseed oil refining: a tool to optimize the health value of edible vegetable oils? Rationale and design of the Optim'Oils randomized clinical trial.

Numerous micronutrients naturally abundant in oilseeds prevent the risk of cardiovascular diseases by reducing cholesterolemia and oxidative stress. These micronutrients include phytosterols and various antioxidants such as polyphenols, tocopherols and coenzyme Q10/Q9 but most of them are lost during the oilseed oil refining. The main objective of the Optim'Oil project was to modify the processes of oil refining in order to reduce the lost of micronutrients. Two clinical trials (cross-over, monocentric, randomized, double-blind and controlled) were designed to investigate the effect of an optimized rapeseed oil 1) on cardiovascular biomarkers (long-term study) and 2) on oxidative stress parameters (post-prandial study). For the long-term study, 59 volunteers ingested daily 20 g of oil and 22 g of margarine (optimized or standard) for 2 periods of 3 weeks separated by a 3-week wash-out period. Blood samples were collected at the beginning and at the end of each period. For the post-prandial study, a sub-group of 16 volunteers came fasted at the laboratory and took 300 mL of a test meal containing 60% of the optimized or standard oils. Blood samples were collected before and during 6h after the test meal intake. In comparison with the standard oil and margarine, the optimized oil and margarine exhibit as expected an increased content of phytosterol (+22%), polyphenols (× 11), tocopherols (+131%) and coenzyme Q10/Q9 (+165%). Overall, conditions of this study were relevant to investigate the effect of the optimized rapeseed oil and margarine on the cardiovascular risk and the oxidative stress.

Alteration of adipocyte metabolism in omega3 fatty acid-depleted rats.

Presently an insufficient supply of long-chain polyunsaturated omega3 fatty acid is prevalent in Western populations leading to potential metabolic consequences. Based on this fact, this study deals mainly with various aspects of lipid metabolism in second generation female omega3-depleted rats. The parametrial fat and body weights were higher in omega3-depleted than control animals. This coincided with liver steatosis but did not alter heart triglyceride/phospholipid ratio. The net uptake of [U-14C] palmitate by adipocytes was also higher in omega3-depleted rats than in control animals. The uptake of D-[U- 4C] glucose or [1,2 (-14)C] acetate by adipocytes was lower, however in omega3-depleted than control animals and was unaffected by insulin in the former as distinct from latter animals. Despite comparable basal lipolysis, the increase in glycerol output from adipocytes provoked by theophylline was higher in omega3-depleted than control rats. The fatty acid pattern of lipids in adipose tissue was characterized in the omega3-depleted rats by a much lower omega3 content, higher apparent Delta 9-saturase and elongase activities, lower efficiency for the conversion of C18:2omega6 to C20:4omega6 and higher efficiency for the conversion of C18:3omega3 to C20:5omega3. These features were compared to those prevailing in liver and plasma lipids. The present study thus extends knowledge on the alteration of lipid metabolism resulting from a deficiency in long-chain polyunsaturated omega3 fatty acids.

Acute in vivo administration of a fish oil-containing emulsion improves post-ischemic cardiac function in n-3-depleted rats.

A novel i.v. lipid preparation (MCT:FO) containing 80% medium chain-triacylglycerols and 20% fish oil was recently developed to rapidly replenish cell membrane phospholipids with omega 3 (n-3) polyunsaturated fatty acids (PUFA). In regard of this property, we investigated the effect of a single i.v. administration of MCT:FO on the recovery of cardiac function after ischemia in control and n-3-depleted rats. Results were compared with those obtained either with a control preparation, where FO was replaced by triolein (MCT:OO), or with saline. Saline (1 ml) or lipid preparation (also 1 ml) was injected as a bolus via the left saphenous vein. After 60 min the heart was removed and perfused for 20 min in normoxic conditions according to Langendorff. Thereafter, the heart was subjected to a 20 min zero-flow normothermic ischemia, followed by 40 min reperfusion. Cardiac mechanical and metabolic functions were monitored. In control rats, the previous administration of a lipid preparation (MCT:FO or MCT:OO) versus saline improved cardiac function during aerobic reperfusion post-ischemia. N-3-depleted rats showed decreased basal cardiac function and impaired recovery following ischemia. However, the bolus injection of MCT:FO opposed the deleterious effect of long-term n-3-deficiency and, in this respect, was superior to MCT:OO over the first 20 min of reperfusion. This novel approach to rapidly correct n-3 PUFA-deficiency might be clinically relevant and offer interesting perspectives in the management of acute ischemic accidents.

Pancreatic islet function in omega-3 fatty acid-depleted rats: alteration of calcium fluxes and calcium-dependent insulin release.

Considering the insufficient supply of long-chain polyunsaturated omega-3 fatty acids often prevailing in Western populations, this report deals mainly with alterations of Ca(2+) fluxes and Ca(2+)-dependent insulin secretory events in isolated pancreatic islets from omega-3-depleted rats. In terms of (45)Ca(2+) handling, the islets from omega-3-depleted rats, compared with those from normal animals, displayed an unaltered responsiveness to an increase in extracellular K(+) concentration, a lower inflow rate and lower fractional outflow rate of the divalent cation, and higher (45)Ca(2+)-labeled cellular pool(s) at isotopic equilibrium. The latter anomaly was corrected 120 min after intravenous injection of a novel medium-chain triglyceride-fish oil (MCT:FO) emulsion, distinct from a control omega-3-poor MCT-olive oil (MCT:OO) emulsion. At 8.3 mM D-glucose, insulin release was higher in islets from omega-3-depleted rats vs. control animals, coinciding with a higher cytosolic Ca(2+) concentration. The relative magnitude of the increase in insulin output attributable to a rise in D-glucose as well as extracellular Ca(2+) or K(+) concentration, to the absence vs. presence of verapamil and to the presence vs. absence of extracellular Ca(2+), theophylline, phorbol 12-myristate 13-acetate, or Ba(2+), was always more pronounced in islets from omega-3-depleted rats injected with the MCT:OO compared with the MCT:FO emulsion. A comparable situation prevailed when comparing islets from noninjected omega-3-depleted and normal rats. In light of these and previous findings, we propose that an impairment of Na(+),K(+)-ATPase activity plays a major, although not an exclusive, role in the perturbation of Ca(2+) fluxes and Ca(2+)-dependent secretory events in the islets from omega-3-depleted rats.

Hepatic steatosis is not due to impaired fatty acid oxidation capacities in C57BL/6J mice fed the conjugated trans-10,cis-12-isomer of linoleic acid.

Decreased body fat mass and liver steatosis have been reported in mice fed diets containing the conjugated linoleic acid trans-10,cis-12-C18:2 (CLA2), but not in those fed diets containing cis-9,trans-11-C18:2 (CLA1). Because the decrease in fatty acid (FA) oxidation may cause fat accumulation, we questioned whether the effects of both CLAs on enzyme activities and mRNA expression were related to liver FA oxidation. To address this question, 7-wk-old male C57BL/6J mice were fed for 4 wk a diet supplemented with 1% CLA1, CLA2, or cis-9-C18:1 (control) esterified as triacylglycerols. In CLA2-fed mice, the proportions of CLA2 in the total FA of liver lipids were substantially lower than those of CLA1 in mice fed CLA1. The mitochondrial protein content per total liver was about 56% greater in CLA2-fed mice than in CLA1-fed mice and controls. Mitochondrial carnitine palmitoyltransferase I (CPT I) and carnitine-dependent palmitate oxidation activities were also significantly greater in CLA2-fed mice than in the two other groups. The amounts of malonyl-CoA per gram of liver and the sensitivity of CPT I to malonyl-CoA inhibition were greater in both groups of CLA-fed mice than in the controls. L-CPT I mRNA expression doubled in CLA2-fed mice and was 3 and 2 times greater for M-CPT I in the CLA1 and CLA2 groups, respectively, compared with controls. Peroxisomal FA oxidation-related activities and acyl-CoA oxidase mRNA expression were increased in CLA1-fed mice, and to a larger extent in CLA2-fed mice, relative to controls. These data indicate that FA oxidation capacities were increased in mice fed CLA2, but were likely depressed in vivo through malonyl-CoA inhibition.

The effect of conjugated linoleic acid isomers on fatty acid profiles of liver and adipose tissues and their conversion to isomers of 16:2 and 18:3 conjugated fatty acids in rats.

Conjugated linoleic acid (CLA) is a collective term that describes different isomers of linoleic acid with conjugated double bonds. Although the main dietary isomer is 9cis,11trans-18:2, which is present in dairy products and ruminant fat, the biological effects of CLA generally have been studied using mixtures in which the 9cis,11trans- and the 10trans,12cis-18:2 were present at similar levels. In the present work, we have studied the impact of each isomer (9cis,11 trans- and 10trans,12cis-18:2) given separately in the diet of rats for 6 wk. The 10trans,12cis-18:2 decreased the triacylglycerol content of the liver (-32%) and increased the 18:0 content at the expense of 18:1 n-9, suggesting an alteration of the delta9 desaturase activity, as was already demonstrated in vitro. This was not observed when the 9cis,11trans-18:2 was given in the diet. Moreover, the 10trans,12cis-18:2 induced an increase in the C22 polyunsaturated fatty acids in the liver lipids. The 10trans,12cis-18:2 was mainly metabolized into conjugated 16:2 and 18:3, which have been identified. The 9cis,11trans isomer was preferentially metabolized into a conjugated 20:3 isomer. Thus, the 9cis,11trans- and the 10trans,12cis-CLA isomers are metabolized differently and have distinct effects on the metabolism of polyunsaturated fatty acids in rat liver while altering liver triglyceride levels differentially.

Dietary trans alpha-linolenic acid from deodorised rapeseed oil and plasma lipids and lipoproteins in healthy men: the TransLinE Study.

TRANS: isomers of alpha-linolenic acid, which are formed by deodorization of refined vegetable oils, can be found in significant amounts in edible oils. Effects of trans alpha-linolenic acid on plasma lipoproteins are unknown. We therefore investigated the effects of trans alpha-linolenic acid on plasma lipids and lipoproteins in healthy European men. Eighty-eight healthy men from three European countries (France, Scotland, UK and the Netherlands) first consumed for 6 weeks a diet with experimental oils 'free' of trans fatty acids (run-in period). For the next 6 weeks, they were randomly allocated to a diet with experimental oils 'high' or 'low' in trans alpha-linolenic acid. Daily total trans alpha-linolenic acid intake in the high trans group was 1410 (range 583-2642) mg. Experimental oils were provided as such, or incorporated into margarines, cheeses, muffins and biscuits. The high trans alpha-linolenic acid diet significantly increased the plasma LDL-:HDL-cholesterol ratio by 8.1 % (95 % CI 1.4, 15.3; and the total cholesterol:HDL-cholesterol ratio by 5.1 % (95 % CI 0.4, 9.9; compared with the low-trans diet. This was largely explained by an increase in LDL-cholesterol on the high-trans diet, while no change was observed in the low-trans group (mean treatment effect of 4.7 % (95 % CI -0.8, 10.5; No effects were found on total cholesterol and HDL-cholesterol, triacylglycerols, apolipoprotein B and A-1, and lipoprotein(a) concentrations. In conclusion, trans alpha-linolenic acid may increase plasma LDL-:HDL-cholesterol and total cholesterol:HDL-cholesterol ratios. Whether diet-induced changes in these ratios truly affects the risk for CHD remains to be established.

Beta-oxidation of conjugated linoleic acid isomers and linoleic acid in rats.

To assess the oxidative metabolism of conjugated linoleic acid (CLA) isomers, rats were force-fed 1.5-2.6 MBq of [1-14C]-linoleic acid (9c,12c-18:2), -rumenic acid (9c,11t-18:2), or-10trans,12cis-18:2 (10t,12c-18:2), and 14CO2 production was monitored for 24 h. The animals were then necropsied and the radioactivity determined in different tissues. Both CLA isomers were oxidized significantly more than linoleic acid. Moreover, less radioactivity was recovered in most tissues after CLA intake than after linoleic acid intake. The substantial oxidation of CLA isomers must be considered when assessing the putative health benefits of CLA supplements.

Incorporation and metabolism of dietary trans isomers of linolenic acid alter the fatty acid profile of rat tissues.

To study the influence on lipid metabolism and platelet aggregation of the fatty acid isomerization that occurs during heat treatment, weanling rats were fed for 8 wk a diet enriched with 5% isomerized (experimental group) or normal (control group) canola oil. Geometrical isomers of alpha-linolenic acid representing 0.2 g/100 g of the experimental diet were incorporated into liver, platelets, aorta and heart, at the expense of their cis homologue and of 18:2(n-6). The major isomer, 9c,12c,15t-18:3, was also metabolized to 5c,8c,11c,14c,17t-20:5 and to an unknown compound, found in liver, platelets and aorta, which has been identified tentatively as 7c, 10c,13c,16c,19t-22:5. The greater 20:4(n-6)/18:2(n-6) ratio in the liver, platelets and heart of the experimental group than the control group indicated an enhancement of desaturation activities. This induced a higher content of long-chain (n-6) fatty acids in the experimental group. Platelet aggregation tended to be slightly higher (P: = 0.065) in the experimental group. We conclude that 0.2 g of trans isomers of alpha-linolenic acid per 100 g of diet was sufficient to be incorporated and metabolized, thus altering the fatty acid profile of rat tissues.

The effect of dietary trans alpha-linolenic acid on plasma lipids and platelet fatty acid composition: the TransLinE study.

OBJECTIVE: To collect (i) baseline data and (ii) execute a large multicentre study examining the effect of trans alpha-linolenic acid on its incorporation into plasma lipids and on risk factors for coronary heart disease. DESIGN: Male volunteers were recruited and the habitual diet assessed by a 4-d weighed record. Fatty acid composition of plasma and platelet lipids were determined by gas chromatography at baseline. After a 6 week run-in period on a trans 'free' diet, male volunteers were randomised to consume 0.6 % of energy trans alpha-linolenic acid or to continue with a diet 'low' in trans alpha-linolenic acid for 6 weeks. SETTING: Three European university research departments supported by the research and development departments of the food industry. SUBJECTS: Male volunteers (88) recruited by local advertisement. METHODS: Replacement of 30 % of the fat of the habitual diet by margarine, oil and foods. Rapeseed oil was deodorised especially to produce the trans 'free' and 'high' trans foods for this study. The incorporation and conversion of trans alpha-linolenic acid into plasma lipids and platelets was assessed by gas chromatography and dietary compliance was verified by 4-d weighed record. RESULTS: Less trans alpha-linolenic acid isomers are incorporated into human plasma lipids in French volunteers than in Dutch or Scottish volunteers consuming their habitual diets. Trans 'free' alpha-linolenic acid-rich oil can be produced by careful deodorization during refining. The 'high' trans diet provided 1410+/-42 mg/d trans isomers of alpha-linolenic acid, whilst the 'low' trans group consumed 60+/-75 mg/d. The change in plasma lipid and platelet fatty acid composition documented that trans linolenic isomers are incorporated and converted to a trans isomer of eicosapentaenoic acid. Only the 15-trans alpha-linolenic acid is incorporated into plasma cholesteryl esters. The group consuming low trans diet had a slightly higher intake of fat, especially saturated and monounsaturated fat. CONCLUSIONS: Trans 'free' rapeseed oil, rich in alpha-linolenic acid, can be produced by careful deodorization. Dietary records show good compliance. Dietary trans isomers of alpha-linolenic acid are incorporated in plasma lipids and converted to long-chain polyunsaturated fatty acids. Their effects on risk factors for coronary heart disease and their metabolism will be reported elsewhere. SPONSORSHIP: European Commission (FAIR 95-0594 grant). European Journal of Clinical Nutrition (2000) 54, 104-113

Identification of novel trans isomers of 20:5n-3 in liver lipids of rats fed a heated oil.

Trans polyunsaturated n-3 fatty acids are formed as a result of the heat treatment of vegetable oils. It was demonstrated previously that the 18:3 delta 9cis, 12 cis, 15 trans containing a cis delta 9 ethylenic bond was converted to a geometrical isomer of 20:5n-3, the 20:5 delta 5 cis, 8 cis, 11 cis, 14 cis, 17 trans. In the present study, we have identified two new isomers of eicosapentaenoic acid, the delta 11 monotrans and the delta 11, 17 ditrans isomers in liver of rats fed a heated oil. These are formed as a result of the conversion of two of the main isomers of linolenic acid which are present in refined and frying oils, the 18:3 delta 9 trans, 12 cis, 15 cis and the 18:3 delta 9 trans, 12 cis, 15 trans.

[Effects of the level of polyunsaturated fatty acids of the diet on the functioning and depletion of energy substrates in the rat heart during perfusion by left atrial route]. / Effets de la teneur en acides gras polyinsaturés du régime sur le fonctionnement et la déplétion en substrats énergétiques de coeur de rat au cours de la perfusion par voie atriale gauche.

The effects of semi-liquid diets containing 6.6% in weight of refined sunflower seed oil (SSO) or hydrogenated coconut oil (HCO) on cardiac endogenous substrates and functional parameters of rats hearts were compared to a standard laboratory chow during seven days. No difference appeared for cardiac glycogen and lipid constituents. Cardiac performance, measured through left atrial perfusion was enhanced by SSO diet and HCO one altered it. A significative phospholipid depletion appeared during the 45 minutes perfusion only in the HCO group.