Changes in Plasma Phospholipid Metabolism Are Associated with Clinical Manifestations of Systemic Sclerosis

Systemic sclerosis (SSc) is an autoimmune disease with fibrosis of the skin and/or internal organs, causing a decrease in quality of life and survival. There is no causative therapy, and the pathophysiology of the SSc remains unclear. Studies showed that lipid metabolism was relevant for autoimmune diseases, but little is known about the role of lipids in SSc. In the present study, we sought to explore the phospholipid profile of SSc by using the lipidomics approach. We also aimed to analyze lipidomics results for different clinical manifestations of SSc. Experiments were performed using high-performance liquid chromatography coupled to mass spectrometry for the lipidomic profiling of plasma samples from patients with SSc. Our study showed, for the first time, significant changes in the level of phospholipids such as plasmalogens and sphingomyelins from the plasma of SSc patients as compared to controls. Phosphatidylcholine plasmalogens species and sphingomyelins were significantly increased in SSc patients as compared to controls. Our results also demonstrated a significant association of changes in the metabolism of phospholipids (phosphatidylcholine and phosphatidylethanolamine plasmalogens species and sphingomyelins) with different clinical manifestations of SSc. Further lipidomic studies might lead to the detection of lipids as new biomarkers or therapeutic targets of SSc.

FADS1 rs174550 genotype and high linoleic acid diet modify plasma PUFA phospholipids in a dietary intervention study

Introduction Fatty acid desaturase 1 (FADS1) gene encodes for delta-5 desaturase enzyme which is needed in conversion of linoleic acid (LA) to arachidonic acid (AA). Recent studies have shown that response to dietary PUFAs differs between the genotypes in circulating fatty acids. However, interactions between the FADS1 genotype and dietary LA on overall metabolism have not been studied. Objectives We aimed to examine the interactions of FADS1 rs174550 genotypes (TT and CC) and high-LA diet to identify plasma metabolites that respond differentially to dietary LA according to the FADS1 genotype. Methods A total of 59 men (TT n = 26, CC n = 33) consumed a sunflower oil supplemented diet for 4 weeks. Daily dose of 30, 40, or 50 ml was calculated based on body mass index. It resulted in 17–28 g of LA on top of the usual daily intake. Fasting plasma samples at the beginning and at the end of the intervention were analyzed with LC–MS/MS non-targeted metabolomics method. Results At the baseline, the carriers of FADS1 rs174550-TT genotype had higher abundance of long-chain PUFA phospholipids compared to the FADS1 rs174550-CC one. In response to the high-LA diet, LA phospholipids and long-chain acylcarnitines increased and lysophospholipids decreased in fasting plasma similarly in both genotypes. LysoPE (20:4), LysoPC (20:4), and PC (16:0_20:4) decreased and cortisol increased in the carriers of rs174550-CC genotype; however, these genotype–diet interactions were not significant after correction for multiple testing. Conclusion Our findings show that both FADS1 rs174550 genotype and high-LA diet modify plasma phospholipid composition. Trial registration The study was registered to ClinicalTrials: NCT02543216, September 7, 2015 (retrospectively registered).

Changes of Plasma Phospholipid Fatty Acids Profiles in Pregnancy in Relation to the Diagnosis and Treatment of Gestational Diabetes Mellitus

Background Plasma phospholipid fatty acids (FAs) in early and mid-pregnancy have been prospectively related to gestational diabetes mellitus (GDM) risk. Yet, changes of FAs following GDM diagnosis and treatment and their implications for glucose metabolism and control remain understudied. Methods From the Eunice Kennedy Shriver National Institute Child Health and Human Development Fetal Growth Studies–Singleton Cohort of 2802 pregnant women, we ascertained 85 GDM cases using the Carpenter and Coustan criteria and 85 non-GDM controls after exclusion. Using plasma collected before (23–31 weeks) and after GDM diagnosis (33–39 weeks), we quantified 25 saturated, poly- and monounsaturated FAs levels. We estimated the fold change of FAs before and after GDM diagnosis, using multiple linear mixed models adjusting for confounders. Results Eight FAs showed significant fold changes from the baseline values (23–31 weeks) among GDM cases as compared to women without GDM. Five FAs showed reduced fold changes [myristic acid (14:0): β: −0.22 (95% CI: −0.30, −0.14), palmitic acid (16:0): β: −0.02 (95% CI: −0.04, −0.01), cis-palmitoleic acid (16:1n7): β: −0.15 (95% CI: −0.24, −0.05), alpha-linolenic acid (18:3n3): β: −0.19 (95% CI: −0.31, −0.07], and dihomo-gamma-linoleic acid (20:3n6): β:−0.16; 95% CI: −0.21, −0.11)], whereas 3 showed increases [heptadecanoic acid (17:0): β: 0.17 (95% CI: 0.11, 0.22), cis-vaccenic acid (18:1n7): β: 0.06 (95% CI: 0.03, 0.10), and arachidonic acid (20:4n6): β: 0.10 (95% CI: 0.06, 0.13)]. Conclusions Our study identified 8 FAs with unique patterns of change before and after GDM diagnosis that differed significantly between women with and without GDM. Our findings may shed light on the role of FA metabolism in the pathophysiology and disease management and progression of GDM. Clinical Trial Registry NCT00912132

Zinc Deficiency, Plasma Fatty Acid Profile and Desaturase Activities in Hemodialysis Patients: Is Supplementation Necessary?

Background: Desaturation and elongation are critical processes in endogenous metabolic fatty acid pathways. Zinc (Zn) is a cofactor for desaturases and elongases enzymes. There is limited evidence regarding the relationships between biomarkers of Zn status, nutritional intake, plasma phospholipid fatty acid profile and clinical outcomes among patients undergoing hemodialysis (HD).Objective: To examine the relationships between dietary and serum levels of Zn and Cu/Zn ratio and to explore associations of these micronutrients with PUFA profile and estimated desaturase and elongase enzyme activities in serum phospholipids among HD patients.Methods: This study included 40 adult patients undergoing hemodialysis treatment. Repeated 24-h recalls were applied for dietary intake assessment. Serum concentration of Zn and Cu were determined using inductively coupled plasma mass spectrometry and fatty acid composition by gas-liquid chromatography. Desaturase and elongase activities were calculated from product-precursor fatty acid ratios.Results: Inadequate dietary Zn intake was found in 55% of HD patients. They all had serum Zn concentration below the reference value of 60 μg/dL (mean 38.8 ± 7.72 μg/dL). Adequate zinc intake was accompanied with significantly higher intake of energy, total fats, SFA, MUFA and proteins. There was no correlation between Zn serum status and Zn intake estimates. Serum Cu/Zn ratio was high, (2.76 ± 0.68), directly and significantly associated with HD period, CRP, BMI, VFA, and inversely with Kt/V, albumin, iron, and iPTH. The n-6/n-3 ratio in plasma phospholipids was elevated (12.25 ± 3.45) and patients with inadequate Zn intake had lower n-3 PUFA intake and status compared to those with adequate intake. Serum Zn concentrations were inversely correlated with linoleic/dihomo-γ-linolenic acid ratio (LA/DGLA) (p = 0.037), related to D6-desaturase activity (p = 0.033) and directly with DGLA relative abundances (p = 0.024). Cu status was inversely associated with EPA level (p = 0.03) and estimates of elongase activity (p = 0.001). Furthermore, positive relationship was found between the Cu/Zn ratio and determined elongase value (p = 0.01).Conclusion: Findings of this study underpin the high prevalence of Zn deficiency and inadequate n-3 PUFA intake and status among subjects undergoing HD. The results obtained indicate that the assessment of Zn status should be a standard parameter of nutritional status screening in HD patients while emphasizing the importance of Cu/Zn determination. Although further research is warranted, Zn and-n-3 PUFA supplementation in HD patients might be beneficial for the prevention and attenuation of adverse health outcomes

Low linoleic acid foods with added DHA given to Malawian children with severe acute malnutrition improves cognition: a randomized, triple blinded, controlled clinical trial

Background: There is concern that the PUFA composition of ready-to-use therapeutic food (RUTF) for treatment of severe acute malnutrition (SAM) is suboptimal for neurocognitive recovery. Objective: We tested the hypothesis that RUTF made with reduced amounts of linoleic acid, achieved using high oleic (HO) peanuts, with or without added DHA, improves cognition when compared to standard RUTF (S-RUTF). Methods: A triple-blind, randomized, controlled clinical feeding trial was conducted among children with uncomplicated SAM in Malawi with 3 types of RUTF; DHA-HO- RUTF, HO-RUTF and S-RUTF. The primary outcomes, measured in a subset of subjects, were the Malawi Developmental Assessment Tool (MDAT) global and 4 domain (gross motor, fine motor, language and social) z-scores and a modified Willatts problem solving assessment (PSA) intention score for 3 standardized problems, measured 6 months and immediately after completing RUTF therapy, respectively. Plasma fatty acid content, anthropometry and eye tracking were secondary outcomes. Comparisons were made between the novel PUFA RUTFs and S-RUTF. Results: Among the 2565 SAM children enrolled, global MDAT z-score was -0.69 ± 1.19 and -0.88 ± 1.27 for children receiving DHA-HO-RUTF and S-RUTF, respectively (difference 0.19, 95% CI 0.01 to 0.38). The gross motor and social domains had higher z-scores among children receiving either DHA-HO-RUTF than S-RUTF. The PSA problem 3 scores did not differ by dietary group (Odds ratio 0.92, 95% CI 0.67 to 1.26 for DHA-HO-RUTF). After 4 weeks of treatment, plasma phospholipid EPA and a- linolenic acid were greater in children consuming DHA-HO-RUTF or HO-RUTF when compared to S-RUTF (for all 4 comparisons P values < 0.001), but only plasma DHA was greater in DHA-HO-RUTF than S-RUTF ( P <0.001). Conclusions: Treatment of uncomplicated SAM with DHA-HO-RUTF resulted in an improved MDAT score, conferring a cognitive benefit six months after completing diet therapy. This treatment should be explored in operational settings.

A 16-week randomized controlled trial of a fish oil and whey protein-derived supplement to improve physical performance in older adults losing autonomy—A pilot study

Background Low functional capacity may lead to the loss of independence and institutionalization of older adults. A nutritional intervention within a rehabilitation program may attenuate loss of muscle function in this understudied population. Objective This pilot study assessed the feasibility for a larger RCT of a nutritional supplementation in older adults referred to an outpatient assessment and rehabilitation program. Methods Participants were randomized to receive a supplement (EXP: 2g fish oil with 1500 IU vitamin D3 1x/d + 20-30g whey protein powder with 3g leucine 2x/d) or isocaloric placebo (CTR: corn oil + maltodextrin powder) for 16 weeks. Handgrip and knee extension strength (using dynamometry), physical performance tests and plasma phospholipid n-3 fatty acids (using GCMS) were evaluated at weeks 0, 8 and 16; and lean soft tissue mass (using DXA), at weeks 0 and 16. Results Over 2 years, 244 patients were screened, 46 were eligible (18.9%), 20 were randomized, 10 completed the study (6 CTR, 4 EXP). Median age was 87 y (77–94 y; 75% women) and gait speed was 0.69 m/s; 55% had low strength, and all performed under 420m on the 6-minute walk test, at baseline. Overall self-reported compliance to powder and oil was high (96% and 85%) but declined at 16 weeks for fish oil (55%). The EXP median protein intake surpassed the target 1.2–1.5 g/kg/d, without altering usual diet. Proportions of plasma phospholipid EPA and DHA increased significantly 3- and 1.5-fold respectively, at week 8 in EXP, with no change in CTR. Participants were able to complete most assessments with sustained guidance. Conclusion Because of low eligibility, the pilot study was interrupted and deemed non-feasible; adherence to rigorous study assessments and to supplements was adequate except for long-term fish oil. The non-amended protocol may be applied to populations with greater functional capacity. Trial registration ClinicalTrials.gov NCT04454359.

Changes in Phospholipid/Ceramide Profiles and Eicosanoid Levels in the Plasma of Rats Irradiated with UV Rays and Treated Topically with Cannabidiol

Chronic UV radiation causes oxidative stress and inflammation of skin and blood cells. Therefore, in this study, we assessed the effects of cannabidiol (CBD), a natural phytocannabinoid with antioxidant and anti-inflammatory properties, on the phospholipid (PL) and ceramide (CER) profiles in the plasma of nude rats irradiated with UVA/UVB and treated topically with CBD. The results obtained showed that UVA/UVB radiation increased the levels of phosphatidylcholines, lysophospholipids, and eicosanoids (PGE2, TxB2), while downregulation of sphingomyelins led to an increase in CER[NS] and CER[NDS]. Topical application of CBD to the skin of control rats significantly upregulated plasma ether-linked phosphatidylethanolamines (PEo) and ceramides. However, CBD administered to rats irradiated with UVA/UVB promoted further upregulation of CER and PEo and led to significant downregulation of lysophospholipids. This was accompanied by the anti-inflammatory effect of CBD, manifested by a reduction in the levels of proinflammatory PGE2 and TxB2 and a dramatic increase in the level of anti-inflammatory LPXA4. It can therefore be suggested that topical application of CBD to the skin of rats exposed to UVA/UVB radiation prevents changes in plasma phospholipid profile resulting in a reduction of inflammation by reducing the level of LPE and LPC species and increasing antioxidant capacity due to upregulation of PEo species.

Progression of Postprandial Blood Plasma Phospholipids Following Acute Intake of Different Dairy Matrices: A Randomized Crossover Trial

Studies have indicated that the dairy matrix can affect postprandial responses of dairy products, but little is known about the effect on postprandial plasma phospholipid levels. This study investigated postprandial plasma phospholipid levels following consumption of four different dairy products that are similar in micro and macro nutrients, but different in texture and structure: cheddar cheese (Cheese), homogenized cheddar cheese (Hom. Cheese), micellar casein isolate with cream (MCI Drink) or a gel made from the MCI Drink (MCI Gel). The study was an acute randomized, crossover trial in human volunteers with four test days. Blood samples were collected during an 8 h postprandial period and the content of 53 plasma phospholipids was analysed using liquid chromatography-mass spectrometry (LC-MS). No meal–time interactions were revealed; however, for nine of the 53 phospholipids, a meal effect was found. Thus, the results indicated a lower plasma level of specific lyso-phosphatidylethanolamines (LPEs) and lyso-phosphatidylcholines (LPCs) following consumption of the MCI Gel compared to the MCI Drink and Hom. Cheese, which might be attributed to an effect of viscosity. However, further studies are needed in order to reveal more details on the effect of the dairy matrix on postprandial phospholipids.