Carole Vaysse

Association of macular pigment density with plasma ω-3 fatty acids: the PIMAVOSA study

PURPOSE To assess the correlation between macular pigment optical density and plasma levels of lutein, zeaxanthin, and fatty acids, especially omega-3 polyunsaturated fatty acids (PUFAs). METHODS The PIMAVOSA study is an observational study of 107 healthy volunteers, aged 20 to 60 years and born in southwest France, without histories of ocular disease. Macular pigment optical density (MPOD) was measured using the two-wavelength autofluorescence method with a modified scanning laser ophthalmoscope. Plasma measurements (lutein, zeaxanthin, and fatty acids) were performed from fasting blood samples collected on the day of the eye examination. RESULTS MPOD within 6° correlated with plasma levels of lutein and zeaxanthin (r = 0.35, P < 0.001, and r = 0.30, P < 0.005, respectively). MPOD also significantly correlated with total plasma omega-3 PUFAs (r = 0.22, P < 0.05). Among the different omega-3 PUFAs, docosapentaenoic acid (DPA) had the highest correlation with MPOD (r = 0.31, P < 0.001), whereas correlation with eicosapentaenoic acid (EPA) was moderate (r = 0.21, P < 0.05) and did not reach statistical significance for docosahexaenoic acid (r = 0.14, P = 0.14). CONCLUSIONS In the present study, macular pigment density was associated not only with plasma lutein and zeaxanthin but also with omega-3 long-chain PUFAs, particularly with EPA and DPA. Further studies will be needed to confirm these findings and to identify the underlying mechanisms.

Dietary emulsifiers from milk and soybean differently impact adiposity and inflammation in association with modulation of colonic goblet cells in high‐fat fed mice

SCOPE Enhanced adiposity and metabolic inflammation are major features of obesity that could be impacted by dietary emulsifiers. We investigated in high-fat fed mice the effects of using a new polar lipid (PL) emulsifier from milk (MPL) instead of soybean lecithin (soybean PL [SPL]) on adipose tissue and intestinal mucosa function. METHODS AND RESULTS Four groups of C57BL6 mice received for 8 wks a low-fat (LF) diet or a high-fat diet devoid of PLs or an high-fat diet including MPL (high-fat-MPL) or SPL (high-fat-SPL). Compared with high-fat diet, high-fat-SPL diet increased white adipose tissue (WAT) mass (p < 0.05), with larger adipocytes (p < 0.05) and increased expression of tumor necrosis factor alpha, monochemoattractant protein-1, LPS-binding protein, and leptin (p < 0.05). This was not observed with high-fat-MPL diet despite similar dietary intakes and increased expression of fatty acid transport protein 4 and microsomal TG transfer protein, involved in lipid absorption, in upper intestine (p < 0.05). High-fat-MPL mice had a lower expression in WAT of cluster of differentiation 68, marker of macrophage infiltration, versus high-fat and high-fat-SPL mice (p < 0.05), and more goblet cells in the colon (p < 0.05). CONCLUSIONS Unlike SPL, MPL in the high-fat diet did not induce WAT hypertrophy and inflammation but increased colonic goblet cells. This supports further clinical exploration of different sources of dietary emulsifiers in the frame of obesity outbreak.

Safety and Tolerance Evaluation of Milk Fat Globule Membrane-Enriched Infant Formulas: A Randomized Controlled Multicenter Non-Inferiority Trial in Healthy Term Infants

Objective This multicenter non-inferiority study evaluated the safety of infant formulas enriched with bovine milk fat globule membrane (MFGM) fractions. Methods Healthy, full-term infants (n = 119) age ≤14 days were randomized to standard infant formula (control), standard formula enriched with a lipid-rich MFGM fraction (MFGM-L), or standard formula enriched with a protein-rich MFGM fraction (MFGM-P). Primary outcome was mean weight gain per day from enrollment to age 4 months (non-inferiority margin: –3.0 g/day). Secondary (length, head circumference, tolerability, morbidity, adverse events) and exploratory (phospholipids, metabolic markers, immune markers) outcomes were also evaluated. Results Weight gain was non-inferior in the MFGM-L and MFGM-P groups compared with the control group. Among secondary and exploratory outcomes, few between-group differences were observed. Formula tolerance rates were high (>94%) in all groups. Adverse event and morbidity rates were similar across groups except for a higher rate of eczema in the MFGM-P group (13.9% vs control [3.5%], MFGM-L [1.4%]). Conclusion Both MFGM-enriched formulas met the primary safety endpoint of non-inferiority in weight gain and were generally well tolerated, although a higher rate of eczema was observed in the MFGM-P group.

The Fraction of α-Linolenic Acid Present in the sn-2 Position of Structured Triacylglycerols Decreases in Lymph Chylomicrons and Plasma Triacylglycerols during the Course of Lipid Absorption in Rats

Little is known about the ability of α-linolenic acid (Ln) to remain in the sn-2 position of TG during the absorption process. The goal of this study was to determine the Ln distribution in the lymph (Study 1) and plasma (Study 2) TG of rats fed a single i.g. load of structured TG [300 mg/rat of either oleic acid (O)/Ln/O TG (OLnO) or Ln/O/O TG (LnOO), n = 7 rats]. In an early fraction (3-4 h) of lymph (OLnO group; 100% Ln in the sn-2 position), 46 ± 2% Ln was maintained in this position in lymph TG. There was even less (29 ± 6%) in the last fraction (7-24 h) (P < 0.05). Ln was also found (9 ± 3%) in the sn-2 position of lymph TG in the LnOO group. The Ln content in lymph phospholipids was twice as high in rats when they were fed LnOO (4.2 ± 0.1%) than OLnO (2.3 ± 0.2%) (P < 0.005). Six hours postprandially (Study 2), 21 ± 3% of the Ln incorporated into plasma TG was located in the sn-2 position in the OLnO group compared to 13 ± 2% in the LnOO group (P < 0.001). Overall, these results indicate that the amount of Ln that moved from the sn-2 position of structured TG to the sn-1(3) position of lymph TG increased during absorption. This may account for a substantial hydrolysis of the 2-monolinolenylglycerols in enterocytes, leading to the intramolecular redistribution of Ln in lymph TG and, consequently, in plasma TG.

Three dimensional morphology of rabies virus studied by cryo-electron tomography

The rabies virus (RABV) continues to be a worldwide health problem. RABV contains a single-stranded RNA genome that associates with the nucleoprotein N. The resulting ribonucleoprotein complex is surrounded by matrix protein M, lipid bilayer and glycoprotein G. RABV was reported to organize in bullet-like virions, but the role of each viral component in adopting this morphology is unclear. We present here a cryo-electron tomography study of RABV showing additional morphologies consisting in bullet-like virions containing a tubular, lipidic appendage having G-protein at its apex. In addition, there was evidence for an important fraction of pleomorphic particles. These pleomorphic forms differed in the amount of membrane-associated M-, M/N-protein providing interesting insight into its role in viral morphogenesis. In the absence of membrane-associated M-, M/N-protein viral morphology was almost spherical. Other images, showing straight membrane portions, correlate with the M-protein recruitment at the membrane independently of the presence of the G-protein. The viral membrane was found to contain a negative net charge indicating that M-, M/N-protein-membrane charge attraction drives this interaction.

Fatty acid composition of adipose tissue and colorectal cancer: a case-control study

BACKGROUND Unlike experimental results, epidemiologic studies that used dietary questionnaires were not convincing as regards the relations between dietary fatty acids (FAs) and risk of colorectal cancer (CRC). The FA composition of adipose tissue, which is considered to be an indicator of dietary intake over 2-3 y because of the slow turnover rate, appears promising but has so far been rarely used to explore the relation between CRC and exogenous or endogenously produced FAs. OBJECTIVE In this case-control study, we aimed to investigate associations between risk of CRC and the FA composition of subcutaneous adipose tissue and product-to-precursor ratios as indexes of enzymatic activities. DESIGN From 2008 to 2011, we recruited 203 cases with newly diagnosed CRC and elective surgery with a curative intent and 223 control subjects with planned abdominal surgery for benign disease and no history of CRC or polyp resection. During surgery, abdominal subcutaneous adipose tissue samples were optimally collected, stored, and analyzed by using high-performance gas chromatography. Multivariate logistic regression was used to estimate ORs for CRC in relation to individual FAs divided into tertiles according to the FA distribution in controls. RESULTS After adjustment, significant positive associations with CRC risk were observed in highest compared with lowest tertiles of 16:1n-9 (OR: 1.75; 95% CI: 1.00, 3.06; P-trend = 0.045), 20:3n-6 (OR: 1.79; 95% CI: 1.01, 3.17; P-trend = 0.038), 22:5n-3 (OR: 1.82; 95% CI: 1.06, 3.12; P-trend = 0.023), and the ratio of 18:2n-6 to 18:3n-3 (OR: 2.34; 95% CI: 1.37, 3.98; P-trend = 0.001). Significant inverse associations were observed for 18:3n-3 (OR: 0.48; 95% CI: 0.29, 0.81; P-trend = 0.007). Several product-to-precursor ratios showed significant differences between cases and controls in particular ratios that reflected elongase 2/5 activity. CONCLUSIONS CRC patients presented higher concentrations of some FAs but lower concentrations of α-linolenic acid in their subcutaneous adipose tissue than did controls. These results may reflect both dietary patterns and altered FA metabolism but require mechanistic explorations.

A high-fat diet induces lower expression of retinoid receptors and their target genes GAP-43/neuromodulin and RC3/neurogranin in the rat brain

Numerous studies have reported an association between cognitive impairment in old age and nutritional factors, including dietary fat. Retinoic acid (RA) plays a central role in the maintenance of cognitive processes via its nuclear receptors (NR), retinoic acid receptor (RAR) and retinoid X receptor (RXR), and the control of target genes, e.g. the synaptic plasticity markers GAP-43/neuromodulin and RC3/neurogranin. Given the relationship between RA and the fatty acid signalling pathways mediated by their respective NR (RAR/RXR and PPAR), we investigated the effect of a high-fat diet (HFD) on (1) PUFA status in the plasma and brain, and (2) the expression of RA and fatty acid NR (RARbeta, RXRbetagamma and PPARdelta), and synaptic plasticity genes (GAP-43 and RC3), in young male Wistar rats. In the striatum of rats given a HFD for 8 weeks, real-time PCR (RT-PCR) revealed a decrease in mRNA levels of RARbeta ( - 14 %) and PPARdelta ( - 13 %) along with an increase in RXRbetagamma (+52 %). Concomitantly, RT-PCR and Western blot analysis revealed (1) a clear reduction in striatal mRNA and protein levels of RC3 ( - 24 and - 26 %, respectively) and GAP-43 ( - 10 and - 42 %, respectively), which was confirmed by in situ hybridisation, and (2) decreased hippocampal RC3 and GAP-43 protein levels (approximately 25 %). Additionally, HFD rats exhibited a significant decrease in plasma ( - 59 %) and brain ( - 6 %) n-3 PUFA content, mainly due to the loss of DHA. These results suggest that dietary fat induces neurobiological alterations by modulating the brain RA signalling pathway and n-3 PUFA content, which have been previously correlated with cognitive impairment.

Erythrocyte DHA level as a biomarker of DHA status in specific brain regions of n-3 long-chain PUFA-supplemented aged rats

n-3 Long-chain PUFA (n-3 LC-PUFA), particularly EPA and DHA, play a key role in the maintenance of brain functions such as learning and memory that are impaired during ageing. Ageing is also associated with changes in the DHA content of brain membranes that could contribute to memory impairment. Limited studies have investigated the effects of ageing and n-3 LC-PUFA supplementation on both blood and brain fatty acid compositions. Therefore, we assessed the relationship between fatty acid contents in plasma and erythrocyte membranes and those in the hippocampus, striatum and cerebral cortex during ageing, and after a 5-month period of EPA/DHA supplementation in rats. In the blood, ageing was associated with an increase in plasma DHA content, whereas the DHA content remained stable in erythrocyte membranes. In the brain, ageing was associated with a decrease in DHA content, which was both region-specific and phospholipid class-specific. In EPA/DHA-supplemented aged rats, DHA contents were increased both in the blood and brain compared with the control rats. The present results demonstrated that n-3 LC-PUFA level in the plasma was not an accurate biomarker of brain DHA status during ageing. Moreover, we highlighted a positive relationship between the DHA levels in erythrocyte phosphatidylethanolamine (PE) and those in the hippocampus and prefrontal cortex in EPA/DHA-supplemented aged rats. Within the framework of preventive dietary supplementation to delay brain ageing, these results suggest the possibility of using erythrocyte PE DHA content as a reliable biomarker of DHA status in specific brain regions.

Effects of Maternal Supplementation With Omega-3 Precursors on Human Milk Composition:

Background: Long-chain polyunsaturated fatty acids (LC-PUFAs) are important for newborn neurosensory development. Supplementation of breastfeeding mothers’ diets with omega-3 PUFAs, such as alpha-linolenic acid (ALA), may increase their concentration in human milk. Research aim: This study aimed to assess human milk composition after 15-day supplementation regimens containing either omega-3 PUFAs or olive oil, which does not provide ALA. Methods: A multicenter factorial randomized trial was conducted with four groups of breastfeeding women, with each group containing 19 to 22 women. After a 15-day ALA washout period, three groups received supplementation with omega-3 precursors for 15 days: an enriched margarine (M), a rapeseed oil (R), and a margarine and rapeseed oil (MR). The fourth was unexposed to omega-3 precursors (olive oil control diet, O). After 15 days, blind determination of human milk fatty acid (FA) composition was assessed by gas chromatography, and the FA composition was compared among groups using variance analyses. Results: Alpha-linolenic acid content, expressed as the mean (standard deviation) total human milk FA percentage, was significantly higher after diet supplementation with omega-3 PUFAs, with values of 2.2% (0.7%) (MR), 1.3% (0.5%) (R), 1.1% (0.4%) (M), and 0.8% (0.3%) (O at D30) (p < .003 for each comparison). The lowest LA–ALA ratio (5.5) was found in the MR group (p < .001). Docosahexaenoic acid and trans FA concentrations did not differ among groups. Conclusion: In lactating women, omega-3 supplementation via the combination of enriched margarine and rapeseed oil increased the ALA content of human milk and generated the most favorable LA–ALA ratio for LC-PUFA synthesis.

Soybean polar lipids differently impact adipose tissue inflammation and the endotoxin transporters LBP and sCD14 in flaxseed vs. palm oil-rich diets

Obesity and type 2 diabetes are nutritional pathologies, characterized by a subclinical inflammatory state. Endotoxins are now well recognized as an important factor implicated in the onset and maintain of this inflammatory state during fat digestion in high-fat diet. As a preventive strategy, lipid formulation could be optimized to limit these phenomena, notably regarding fatty acid profile and PL emulsifier content. Little is known about soybean polar lipid (SPL) consumption associated to oils rich in saturated FA vs. anti-inflammatory omega-3 FA such as α-linolenic acid on inflammation and metabolic endotoxemia. We then investigated in mice the effect of different synthetic diets enriched with two different oils, palm oil or flaxseed oil and containing or devoid of SPL on adipose tissue inflammation and endotoxin receptors. In both groups containing SPL, adipose tissue (WAT) increased compared with groups devoid of SPL and an induction of MCP-1 and LBP was observed in WAT. However, only the high-fat diet in which flaxseed oil was associated with SPL resulted in both higher WAT inflammation and higher circulating sCD14 in plasma. In conclusion, we have demonstrated that LPS transporters LBP and sCD14 and adipose tissue inflammation can be modulated by SPL in high fat diets differing in oil composition. Notably high-flaxseed oil diet exerts a beneficial metabolic impact, however blunted by PL addition. Our study suggests that nutritional strategies can be envisaged by optimizing dietary lipid sources in manufactured products, including fats/oils and polar lipid emulsifiers, in order to limit the inflammatory impact of palatable foods.