Spirulina liquid extract prevents metabolic disturbances and improves liver sphingolipids profile in hamster fed a high-fat diet.

PURPOSE: Metabolic syndrome is characterized by hyperglycemia, hyperlipemia and exacerbated oxidative stress. The aim of the study was to determine whether Spirulysat®, a Spirulina liquid extract (SLE) enriched in phycocyanin, would prevent metabolic abnormalities induced by high-fat diet. METHODS: The effect of acute SLE supplementation on postprandial lipemia and on triton-induced hyperlipidemia was studied in hamster fed control diet (C). The effect of chronic SLE supplementation on lipid content in plasma, liver and aorta, and on glycemia and oxidative stress was studied in hamster fed control (C) or high-fat diet (HF) for two weeks and then treated with SLE for two weeks (CSp and HFSp) or not (C and HF). RESULTS: The acute SLE supplementation lowered plasma cholesterol and non-esterified fatty acid concentrations after olive oil gavage (P < 0.05) in CSp, while no effect was observed on triglyceridemia. HFD increased plasma MDA, basal glycemia, triglyceridemia, total plasma cholesterol, VLDL, LDL and HDL cholesterol, ceramide, sphingomyelin and glucosylceramide content in liver in HF compared to C (P < 0.05). SLE did not affect SOD and GPx activities nor total antioxidant status in HFSp group but lowered glycemia, glucoceramide and cholesterol in liver and cholesterol in aorta compared to HF (P < 0.05). SLE also decreased HMGCoA and TGF-ß1 gene expression in liver (P < 0.05) and tended to lower G6Pase (P = 0.068) gene expression in HFSp compared to HF. CONCLUSION: Although 2-week SLE supplementation did not affect oxidative stress, it protected from hyperglycemia and lipid accumulation in liver and aorta suggesting a protective effect against metabolic syndrome.

Omega 3 Improves Both apoB100-containing Lipoprotein Turnover and their Sphingolipid Profile in Hypertriglyceridemia.

CONTEXT: Evidence for an association between sphingolipids and metabolic disorders is increasingly reported. Omega-3 long-chain polyunsaturated fatty acids (n-3 LC-PUFAs) improve apolipoprotein B100 (apoB100)-containing lipoprotein metabolism, but their effects on the sphingolipid content in lipoproteins remain unknown. OBJECTIVES: In subjects with hypertriglyceridemia, we analyzed the effect of n-3 LC-PUFAs on the turnover apoB100-containing lipoproteins and on their sphingolipid content and looked for the possible association between these lipid levels and apoB100-containing lipoprotein turnover parameters. METHODS: Six subjects underwent a kinetic study before and after n-3 supplementation for 2 months with 1 g of fish oil 3 times day containing 360 mg of eicosapentaenoic acid (EPA) and 240 mg of docosahexaenoic acid (DHA) in the form of triglycerides. We examined apoB100-containing lipoprotein turnover by primed perfusion labeled [5,5,5-2H3]-leucine and determined kinetic parameters using a multicompartmental model. We quantified sphingolipid species content in lipoproteins using mass spectrometry. RESULTS: Supplementation decreased very low-density lipoprotein (VLDL), triglyceride, and apoB100 concentrations. The VLDL neutral and polar lipids showed increased n-3 LC-PUFA and decreased n-6 LC-PUFA content. The conversion rate of VLDL1 to VLDL2 and of VLDL2 to LDL was increased. We measured a decrease in total apoB100 production and VLDL1 production. Supplementation reduced the total ceramide concentration in VLDL while the sphingomyelin content in LDL was increased. We found positive correlations between plasma palmitic acid and VLDL ceramide and between VLDL triglyceride and VLDL ceramide, and inverse correlations between VLDL n-3 LC-PUFA and VLDL production. CONCLUSION: Based on these results, we hypothesize that the improvement in apoB100 metabolism during n-3 LC-PUFA supplementation is contributed to by changes in sphingolipids.

Maternal supplementation with citrulline or arginine during gestation impacts fetal amino acid availability in a model of intrauterine growth restriction (IUGR).

BACKGROUND: Supplementing maternal diet with citrulline or arginine during gestation was shown to enhance fetal growth in a model of IUGR induced by maternal dietary protein restriction in the rat. OBJECTIVE: The aims of this study were to determine in the same model whether maternal supplementation with citrulline or arginine would increase 1) citrulline and arginine concentration in fetal circulation; 2) the expression of placental amino acid transporters, and 3) the fetal availability of essential amino acids. METHODS: Pregnant rats (n = 8 per group) were fed either an isocaloric control (20% protein, NP) or a low protein (LP, 4% protein) diet, either alone or supplemented with 2 g/kg/d of l-citrulline (LP + CIT) or isonitrogenous Arginine (LP + ARG) in drinking water throughout gestation. Fetuses were extracted by C-section on the 21st day of gestation. The gene expression of system A (Slc38a1, Slc38a2, and Slc38a4) and L (Slc7a2, Slc7a5, Slc7a8) amino acid transporters was measured in placenta and amino acid concentrations determined in maternal and fetal plasma. RESULTS: Maternal LP diet decreased fetal (4.01 ± 0.03 vs. 5.45 ± 0.07 g, p < 0.0001) and placental weight (0.617 ± 0.01 vs. 0.392 ± 0.04 g, p < 0.001), by 26 and 36% respectively, compared with NP diet. Supplementation with either CIT or ARG increased fetal birth weight by ≈ 5 or 11%, respectively (4.21 ± 0.05 and 4.48 ± 0.05 g vs. 4.01 ± 0.03 g, p < 0.05). CIT supplementation produced a 5- and 2-fold increase in fetal plasma citrulline and arginine, respectively, whereas ARG supplementation only increased fetal arginine concentration. LP diet led to lower placental SNAT 4 mRNA, and higher LAT2 and SNAT1 expression, compared with NP. SNAT4, 4hFC, LAT2 mRNA were up-regulated in LP + CIT and LP + ARG group compared with the un-supplemented LP group. Higher level of LAT1 mRNA was also observed in the LP + CIT group than in the LP group (p < 0.01). SNAT2 expression was unchanged in response to CIT or ARG supplementation. Fetal amino acid concentrations were decreased by LP diet, and were not restored by CIT or ARG supplementation. CONCLUSIONS: The current findings confirm supplementation with citrulline or arginine enhances fetal growth in a rat model of IUGR. They further suggest that: 1) citrulline and arginine administered orally to the pregnant mother may reach fetal circulation; 2) citrulline effectively raises fetal arginine availability; and 3) although it failed to increase the concentrations of essential amino acids in fetal plasma, citrulline or arginine supplementation upregulates the gene expression of several placental amino acid transporters.

Direct and maternal n-3 long-chain polyunsaturated fatty acid supplementation improved triglyceridemia and glycemia through the regulation of hepatic and muscle sphingolipid synthesis in offspring hamsters fed a high-fat diet.

PURPOSE: We recently reported that direct and maternal supplementation with n-3 long-chain polyunsaturated fatty acids (n-3 LC-PUFA) alleviates the metabolic disturbances in adult hamster pups fed with a high-fat diet (HFD). In this study, we hypothesized that these results involved a perinatal modulating effect of sphingolipids by n-3 LC-PUFA. METHODS: We studied the effect of direct and maternal n-3 LC-PUFA supplementation on sphingolipid contents in liver and muscle, hepatic triglycerides (TG) secretion and glucose tolerance. Offspring male hamsters born from supplemented (Cω) or unsupplemented (C) mothers were subjected after weaning to a HFD during 16 weeks, without (Cω-HF or C-HF) or with direct supplementation with n-3 LC-PUFA (C-HFω). RESULTS: Direct supplementation decreased sphingosine, sphinganine and ceramides in liver and decreased sphingosine, sphinganine, sphingosine-1-phosphate (S1P) and ceramides in muscle in C-HFω compared to C-HF (p < 0.05). Maternal supplementation decreased C20 ceramide and lactosylceramide in liver and sphinganine, S1P and lactosylceramide in muscle (p < 0.05). This supplementation tended to decrease glucosylceramide in liver (p < 0.06) and muscle (p < 0.07) in Cω-HF compared to C-HF. Direct supplementation increased glucose tolerance and decreased hepatic TG secretion and hepatic gene expression levels of diacylglycerol O-acyltransferase 2 (DGAT2), sterol regulatory element-binding protein-1c (SREBP-1c), fatty acid synthase, stearoyl-CoA desaturase-1 (SCD1) and tumor necrosis factor α (TNFα). Maternal supplementation decreased basal glycemia and hepatic TG secretion. We observed a positive correlation between hepatic TG secretion and hepatic ceramide (p = 0.0059), and between basal glycemia and hepatic ceramide (p = 0.04) or muscle lactosylceramide contents (p = 0.001). CONCLUSION: We observed an improvement of lipids and glucose metabolism in hamster with n-3 LC-PUFA direct supplementation and a decrease in glycemia and hepatic TG secretion with maternal supplementation. These results are probably related to a decrease in both lipogenesis and sphingolipid contents in liver and muscle.

Maternal supplementation with n-3 long chain polyunsaturated fatty acids during perinatal period alleviates the metabolic syndrome disturbances in adult hamster pups fed a high-fat diet after weaning.

Perinatal nutrition is thought to affect the long-term risk of the adult to develop metabolic syndrome. We hypothesized that maternal supplementation with eicosapentaenoic acid and docosahexaenoic acid during pregnancy and lactation would protect offspring fed a high-fat diet from developing metabolic disturbances. Thus, two groups of female hamsters were fed a low-fat control diet, either alone (LC) or enriched with n-3 long chain polyunsaturated fatty acids (LC-PUFA) (LO), through the gestational and lactation periods. After weaning, male pups were randomized to separate groups that received either a control low-fat diet (LC) or a high-fat diet (HC) for 16 weeks. Four groups of pups were defined (LC-LC, LC-HC, LO-LC and LO-HC), based on the combinations of maternal and weaned diets. Maternal n-3 LC-PUFA supplementation was associated with reduced levels of basal plasma glucose, hepatic triglycerides secretion and postprandial lipemia in the LO-HC group compared to the LC-HC group. Respiratory parameters were not affected by maternal supplementation. In contrast, n-3 LC-PUFA supplementation significantly enhanced the activities of citrate synthase, isocitrate dehydrogenase and α-ketoglutarate dehydrogenase compared to the offspring of unsupplemented mothers. Sterol regulatory element binding protein-1c, diacylglycerol O-acyltransferase 2, fatty acid synthase, stearoyl CoA desaturase 1 and tumor necrosis factor α expression levels were not affected by n-3 LC-PUFA supplementation. These results provide evidence for a beneficial effect of n-3 LC-PUFA maternal supplementation in hamsters on the subsequent risk of metabolic syndrome. Underlying mechanisms may include improved lipid metabolism and activation of the mitochondrial oxidative pathway.

Cord blood glutathione depletion in preterm infants: correlation with maternal cysteine depletion.

BACKGROUND: Depletion of blood glutathione (GSH), a key antioxidant, is known to occur in preterm infants. OBJECTIVE: Our aim was to determine: 1) whether GSH depletion is present at the time of birth; and 2) whether it is associated with insufficient availability of cysteine (cys), the limiting GSH precursor, or a decreased capacity to synthesize GSH. METHODOLOGY: Sixteen mothers delivering very low birth weight infants (VLBW), and 16 mothers delivering healthy, full term neonates were enrolled. Immediately after birth, erythrocytes from umbilical vein, umbilical artery, and maternal blood were obtained to assess GSH [GSH] and cysteine [cys] concentrations, and the GSH synthesis rate was determined from the incorporation of labeled cysteine into GSH in isolated erythrocytes ex vivo, measured using gas chromatography mass spectrometry. PRINCIPAL FINDINGS: Compared with mothers delivering at full term, mothers delivering prematurely had markedly lower erythrocyte [GSH] and [cys] and these were significantly depressed in VLBW infants, compared with term neonates. A strong correlation was found between maternal and fetal GSH and cysteine levels. The capacity to synthesize GSH was as high in VLBW as in term infants. CONCLUSION: The current data demonstrate that: 1) GSH depletion is present at the time of birth in VLBW infants; 2) As VLBW neonates possess a fully active capacity to synthesize glutathione, the depletion may arise from inadequate cysteine availability, potentially due to maternal depletion. Further studies would be needed to determine whether maternal-fetal cysteine transfer is decreased in preterm infants, and, if so, whether cysteine supplementation of mothers at risk of delivering prematurely would strengthen antioxidant defense in preterm neonates.

Oral citrulline does not affect whole body protein metabolism in healthy human volunteers: results of a prospective, randomized, double-blind, cross-over study.

BACKGROUND & AIMS: Citrulline increases protein synthesis during refeeding in rodents with short bowel syndrome, aging and malnutrition, and improves nitrogen balance in fed healthy humans. The aim of the current study therefore was to determine whether citrulline had affected protein metabolism in healthy volunteers. METHODS: In a randomized, double-blind, cross-over study, 12 healthy adults received a 5-h intravenous infusion of L-[1-(13)C]-leucine in the post-absorptive state, after a 7-day oral supplementation with 0.18 g/kg/day citrulline, or an iso-nitrogenous placebo. Treatment order was randomized, treatment periods were separated by 13-day wash out. Leucine appearance rate (Ra) was determined from plasma [1-(13)C]-keto-iso-caproate enrichment and leucine oxidation from expired (13)CO(2), and nitrogen balance was estimated from 6-h urinary urea excretion. RESULTS: Compared with placebo, oral citrulline supplementation increased plasma citrulline, arginine and ornithine concentrations, but failed to affect albumin, transthyretin, free insulin and insulin-like growth factor (IGF)-1 plasma concentrations, urinary nitrate excretion, or nitrogen balance. Citrulline supplementation did not alter leucine Ra, leucine oxidation, nor whole-body protein synthesis. CONCLUSION: In healthy, well nourished volunteers, oral citrulline increases plasma citrulline and arginine availability but does not affect whole-body protein kinetics in the post-absorptive state.