Lipid-soluble Vitamins Research Articles

Total Lipids, Fatty Acid Composition, Total Cholesterol and Lipid-Soluble Antioxidant Vitamins in the longissimus lumborum Muscle of Water Buffalo (Bubalus bubalis) from Different Production Systems of the Brazilian Eastern Amazon.

Simple SummaryThe constant search for higher living standards and better health makes consumers more aware of the nutritional compositions of foods. Water buffalo meat has so far been poorly characterized. In this work, we have analyzed the influence of different production systems in the Eastern Amazon on meat nutritional quality parameters of water buffalo. Meat nutritional value was improved when buffaloes were reared in Marajó Island extensive system during the rainy season, as it had lower levels of cholesterol and higher amounts of α-tocopherol, associated with a higher h/H ratio and a lower index of atherogenic. Also, this meat had lower levels of saturated fatty acids and higher amounts of mono- and polyunsaturated fatty acids. Overall, meat from buffaloes raised in pasture production systems showed better lipid nutritional quality.The aim of this study was to analyze the influence of distinct production systems and seasonal variation in the Brazilian Eastern Amazon on the meat lipid composition of water buffaloes. Water buffaloes were reared in commercial farms in the Eastern Amazon either in extensive systems (Marajó Island, Nova Timboteua and Santarém locations), during rainy or dry seasons, or intensive (feedlot) systems. Animals reared in extensive systems were fed natural pastures, and those reared in feedlots were fed sorghum silage and commercial pellets. Buffaloes were slaughtered and ribeye muscle (longissimus lumborum) samples collected. Lipid-soluble antioxidant vitamins and fatty acids were analyzed. The nutritional value of meat from buffaloes reared in Marajó Island extensive system during the rainy season was higher than that of other systems, as it had lower levels of cholesterol and higher amounts of α-tocopherol associated with higher hypocholesterolaemic/hypercholesterolaemic ratio and lower index of atherogenic. Also, this meat had lower percentages of saturated fatty acids and higher proportions of mono- and polyunsaturated fatty acids (PUFA), particularly n-3 PUFA, with increased PUFA/saturated fatty acids ratio and decreased n-6/n-3 PUFA ratio. However, all extensive systems produced meat with a relatively low index of thrombogenicity values, which is advantageous for human health.

Biochemical parameters and antioxidant property of three Salvia L. taxa endemic in Turkey.

The aim of the present study was to determine and compare the fatty acids, lipid soluble vitamins, sterols, phenolics, and antioxidant capacities of three endemic Salvia L. taxa (S. euphratica var. Montbret & Aucher ex Bentham leiocalycina (Rech. Fil.) Hedge, S. euphratica var. Montbret & Aucher ex Bentham euphratica (Rech. Fil.) Hedge and S. pseudoeuphratica Rech.Fil.) and to evaluate these results systematically. The fatty acid compositions were determined by using gas chromatography, while the lipid soluble vitamins, sterols, and phenolics were determined by using HPLC. Also, the antioxidant capacities of three Salvia taxa were measured in vitro. Palmitic acid was found as major saturated fatty acid while oleic acid, linoleic acid, α-linolenic acid, and erucic acid were found as major unsaturated fatty acids in the present study. It was found that S. euphratica var. euphratica had lower palmitic acid (8.94 ± 0.71%), total saturated fatty acid (19.16 ± 0.15%), and higher unsaturated fatty acid content (82.08 ± 0.52%) than other studied taxa. Furthermore, it was shown that S. euphratica var. euphratica had different 18.3/18:2 (0.36) unsaturated/saturated fatty acid (4.28) ratios. However, this study demonstrated that Salvia taxa had low lipid soluble vitamins, sterol contents. On the other hand, it was shown that Salvia taxa had similar catechin (509.2 ± 4.21 µg/g and 552.2 ± 9.21 µg/g) and vanillic acid amounts (351.2 ± 2.17 µg/g and 396.8 ± 4.1 µg/g) in this study. And also, it was found that Salvia taxa had high rosmarinic acid content while S. euphratica var. leiocalycina had the highest rosmarinic acid content (1480 ± 7.57 µg/g). On the other hand, it was shown that the two ferulic acid contents of S. euphratica varieties were higher (1175 ±/5.21 µgmg-1740.2 ± 4.82 µg/mg) than the ferulic acid content of S. pseudoeuphratica of which was the lowest (19.2 ± 0.97 µg/mg). The present results suggested that the biochemical results guided the morphological studies, and Salvia taxa have a potent antioxidant capacity.

Delta-Tocopherol Suppresses the Dysfunction of Thermogenesis due to Inflammatory Stimulation in Brown Adipocytes.

Brown adipose tissue (BAT) functions as a radiator for thermogenesis and helps maintain body temperature and regulate metabolism. Inflammatory signals have been reported to inhibit PGC-1α activation and UCP1-mediated thermogenesis in brown adipocytes. Inflammation is mainly caused by cell hypertrophy and macrophage invasion due to obesity, and invading macrophages secrete inflammatory cytokines, including TNF-α, IL1β, and IL6, which suppress the thermogenesis in BAT. Tocopherol is a lipid-soluble vitamin with anti-inflammatory effects is expected to contribute to the suppression of inflammation in adipose tissue. In this study, we investigated the protective effect of tocopherols, α-tocopherol (α-toc) and δ-tocopherol (δ-toc), against brown adipocyte inflammation and thermogenesis dysfunction.Inflammatory stimulation by TNF-α, a major inflammatory cytokine, significantly decreased the protein expression levels of UCP1 and PGC-1α in rat primary brown adipocytes. The pre-incubation of α-toc or δ-toc significantly suppressed the decrease in UCP1 and PGC-1α expression and lipid accumulation. Additionally, α-toc and δ-toc suppress the induction of ERK1/2 gene expression, implying that an antiinflammatory effect is involved in this protective effect. We fed mice a high-fat diet for 16 weeks and investigated the effects of α-toc and δ-toc in the diet. Intake of α-toc and δ-toc significantly suppressed weight gain and hypertrophy of brown adipocytes. Our results suggest that α-toc and δ-toc suppress the dysfunction of thermogenesis in brown adipocytes due to inflammation and contribute to the treatment of obesity and obesity-related metabolic diseases.

Profiling of Essential Mineral Content, Heavy Metals, and Bacterial Contaminants in Conventional and Organic Eggs Available in the Hypermarkets of the Eastern Province of Saudi Arabia

Eggs are commonly regarded as one of the best sources of various macro and micronutrients, in particular, high biological value (BV) proteins and both saturated and unsaturated fatty acids. Apart from proteins, eggs are excellent sources of various high health value lipid components, carotenoids, minerals, and both water and lipid-soluble vitamins. However, the nutrient-rich nature of this 'superfood' also makes them susceptible to microbial contamination from various sources, such as fecal matter, drinking water for layer chicken, and the surrounding environment. Moreover, drinking water and chicken feed are also sources of heavy metal contamination. The presence of both factors poses serious health concerns for consumers. The main aim of this research was to proximate heavy metals and bacterial contaminants in nine different brands of brown organic and conventional white eggs available in the hypermarkets of the Eastern Province of Saudi Arabia. An Inductively Coupled Plasma-Optical Emission Spectrometer (ICP-OES) was used to determine the concentration of metals with high sensitivity. Standard plate count was followed by enrichment of bacterial contaminants in a double-strength nutrient broth medium for microbiological assessment. The results indicated that Pb, Cd, Al, and As were present in high concentrations in all egg brands of both types (organic and conventional). The estimated daily intake (EDI) values for Ca, Fe, Mn, and Mg were within the range of WHO-recommended thresholds, and these essential minerals were present in adequate amounts in all egg brands. The two major groups predominating the microbial loads were the family Enterobacteriaceae and Pseudomonas sp. The presence of heavy metals, such as Al, As, Pb, and Cd, in nearly all the brands in amounts that exceeded the established ADI and EDI thresholds was considerably concerning. In particular, the elevated levels of Cd and Pb in group 1 and group 2A probable human carcinogens, respectively, demands that local regulatory authorities investigate the sources of heavy metal contamination and alleviate this considerable risk to human health. Furthermore, this study could be a benchmark for establishing food safety and hygiene standards for local egg production, storage, handling, and transport in Saudi Arabia.

Phytonutrients and Metabolism Changes in Topped Radish Root and Its Detached Leaves during 1 °C Cold Postharvest Storage

Glucosinolates, lipid-soluble vitamins E and K contents, primary metabolites and plant hormones were analyzed from topped radish root and detached leaf during storage at 1 °C. The topped root was analyzed at 0, 5, 15, 30, and 90 days after storage while the detached leaf was analyzed at 0, 5, 15, 30, and 45 days in an airtight storage atmosphere environment. The results showed that aliphatic glucosinolates were gradually decreased in leaf but not in root. There was a highly significant correlation between tryptophan and 4-methoxyindoleglucobrassicin in both tissues (r = 0.922, n = 10). There was no significant difference in vitamins E and K in leaf and root during storage. Plant hormones partially explained the significantly changed metabolites by tissue and time, which were identified during cold storage. Phenylalanine, lysine, tryptophan, and myo-inositol were the most important biomarkers that explained the difference in leaf and root tissue during cold storage. The most different metabolism between leaf and root tissue was starch and sucrose metabolism. Therefore, different postharvest technology or regimes should be applied to these tissues.

The biochemical content and antioxidant capacities of endemic Tanacetum densum (Lab.) Schultz Bip. subsp. laxum, and Tanacetum densum (Lab.) Schultz Bip. subsp. amani Heywood growing in Turkey.

Medicinal plants have a significant role in preventing and curing several diseases, and Tanacetum L. is one of these plants. The aim of the present study is to determine the fatty acid, lipid-soluble vitamin, sterol, phenolic content, and antioxidant capacity of Tanacetum densum subsp. laxum and Tanacetum densum subsp. amani, to compare the effect of altitude on the biochemical content and to compare systematically by using fatty acids and phenolics. This study showed that palmitic acid (C16:0) and stearic acid (C18:0) are major sources of saturated fatty acid and oleic acid (C18:1 n9), and linoleic acid (18:2 n6c) and a-linolenic acid (C18:3 n3) are the principal unsaturated fatty acids in the two endemic Tanacetum densum taxa. Also, this study found that the unsaturated fatty acid content (60.11±1.61%) of Tanacetum densum subsp. laxum was higher than the unsaturated fatty acid content (44.13±1.28%) of Tanacetum densum subsp. amani. And also, the ω6/ω3 ratio of Tanacetum densum subsp. laxum (1.74) and Tanacetum densum subsp. amani (1.60) was found to be similar. However, this study determined that the lipid soluble vitamin and sterol content of two endemic Tanacetum taxa are low except for stigmasterol. Present study showed that catechin is principal phenolic in the Tanacetum densum taxa. This study also found that Tanacetum densum subsp. laxum and Tanacetum densum subsp. amani had the highest levels of catechin, vanillic acid, and caffeic acid content though the phenolic amounts, particularly catechin and quercetin, were dissimilar in the T. densum taxa. This study suggested that ecological conditions such as altitude may affect the biochemical content of two endemic Tanacetum densum taxa. Furthermore, the current study determined that two endemic Tanacetum L. taxa had potent radical scavenging capacities and found a correlation between total phenolics and antioxidant activity.

Lipid-soluble vitamins from dairy products: Extraction, purification, and analytical techniques

Milk and dairy products are considered as essential sources of lipid-soluble vitamins (LSVs) for human nutrition. Due to the lower concentrations, complexity, and instability of LSVs during extraction, their quantification remains challenging. This review focus on advances in the extraction and quantification of LSVs from different dairy products. Saponification, and liquid-liquid (LLE), solid-phase (SPE), and supercritical fluid (SFE) extraction methods, as well as dispersive liquid-liquid microextraction, are the most common techniques. Liquid chromatography-mass spectrophotometry (LC-MS) has unique advantages for LSVs determination and quantification due to its high sensitivity and specificity.

Mediterranean Diet Affects Blood Circulating Lipid-Soluble Micronutrients and Inflammatory Biomarkers in a Cohort of Breast Cancer Survivors: Results from the SETA Study

Breast cancer (BC) is a major public health concern and substantial research has shown that adhering to a healthy dietary pattern, such as the Mediterranean Diet (MD), may prevent the onset of cancer and BC relapses. This study aims at specifically investigating the association of MD with circulating dietary-related biomarkers in a cohort of BC survivors. Eighty patients (mean age of 54.9 ± 10.6) with a histologically confirmed diagnosis of BC who had not received any pharmacological or radiotherapy treatment for at least two months were enrolled. Fasting serum lipid-soluble vitamins (retinol, tocopherol), plant pigments (β-carotene, lutein + zeaxanthin, cryptoxanthin, lycopene), inflammatory and oxidative stress markers (ceruloplasmin; haptoglobin; paraoxonases; reactive oxygen molecule; thiol groups, Ferric reducing antioxidant power), and cardiometabolic parameters (body mass index (BMI); glucose; insulin; HOMA-IR; total cholesterol; LDL-cholesterol; HDL-cholesterol; triglycerides) were analyzed. Adherence to the MD was assessed through the Mediterranean Diet Score (MDS) questionnaire. Fasting blood samples were collected for the evaluation of selected biomarkers. MDS resulted positively correlated with β-carotene (r 0.331; p < 0.01) and lycopene (r 0.274; p < 0.05) and negatively with retinol (r −0.346; p < 0.05). Among the investigated inflammatory biomarkers, MDS was only correlated with antioxidant capacity (r 0.256; p < 0.05), while none of the investigated cardiometabolic parameters were significantly correlated with this index. The strong significant correlation between β-carotene and MDS encourages us to consider this pro-vitamin as a putative biomarker to take into account for evaluating the adherence to the MD.

The Role of Vitamins in Neurodegenerative Disease: An Update.

Acquiring the recommended daily allowance of vitamins is crucial for maintaining homeostatic balance in humans and other animals. A deficiency in or dysregulation of vitamins adversely affects the neuronal metabolism, which may lead to neurodegenerative diseases. In this article, we discuss how novel vitamin-based approaches aid in attenuating abnormal neuronal functioning in neurodegeneration-based brain diseases such as Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, Amyotrophic lateral sclerosis, and Prion disease. Vitamins show their therapeutic activity in Parkinson’s disease by antioxidative and anti-inflammatory activity. In addition, different water- and lipid-soluble vitamins have also prevented amyloid beta and tau pathology. On the other hand, some results also show no correlation between vitamin action and the prevention of neurodegenerative diseases. Some vitamins also exhibit toxic activity too. This review discusses both the beneficial and null effects of vitamin supplementation for neurological disorders. The detailed mechanism of action of both water- and lipid-soluble vitamins is addressed in the manuscript. Hormesis is also an essential factor that is very helpful to determine the effective dose of vitamins. PubMed, Google Scholar, Web of Science, and Scopus were employed to conduct the literature search of original articles, review articles, and meta-analyses.

Pharmacologic and genetic inhibition of cholesterol esterification enzymes reduces tumour burden: A systematic review and meta-analysis of preclinical models

Cholesterol esterification proteins Sterol-O acyltransferases (SOAT) 1 and 2 are emerging prognostic markers in many cancers. These enzymes utilise fatty acids conjugated to coenzyme A to esterify cholesterol. Cholesterol esterification is tightly regulated and enables formation of lipid droplets that act as storage organelles for lipid soluble vitamins and minerals, and as cholesterol reservoirs. In cancer, this provides rapid access to cholesterol to maintain continual synthesis of the plasma membrane. In this systematic review and meta-analysis, we summarise the current depth of understanding of the role of this metabolic pathway in pan-cancer development. A systematic search of PubMed, Scopus, Web of Science, and Cochrane Library for preclinical studies identified eight studies where cholesteryl ester concentrations were compared between tumour and adjacent-normal tissue, and 24 studies where cholesterol esterification was blocked by pharmacological or genetic approaches. Tumour tissue had a significantly greater concentration of cholesteryl esters than non-tumour tissue (p < 0.0001). Pharmacological or genetic inhibition of SOAT was associated with significantly smaller tumours of all types (p ≤ 0.002). SOAT inhibition increased tumour apoptosis (p = 0.007), CD8 + lymphocyte infiltration and cytotoxicity (p ≤ 0.05), and reduced proliferation (p = 0.0003) and metastasis (p < 0.0001). Significant risk of publication bias was found and may have contributed to a 32% overestimation of the meta-analysed effect size. Avasimibe, the most frequently used SOAT inhibitor, was effective at doses equivalent to those previously reported to be safe and tolerable in humans. This work indicates that SOAT inhibition should be explored in clinical trials as an adjunct to existing anti-neoplastic agents.

Bile acid homeostasis in female mice deficient in Cyp7a1 and Cyp27a1

Bile acids (BAs) are amphipathic molecules important for metabolism of cholesterol, absorption of lipids and lipid soluble vitamins, bile flow, and regulation of gut microbiome. There are over 30 different BA species known to exist in humans and mice, which are endogenous modulators of at least 6 different membrane or nuclear receptors. This diversity of ligands and receptors play important roles in health and disease; however, the full functions of each individual BA in vivo remain unclear. We generated a mouse model lacking the initiating enzymes, CYP7A1 and CYP27A1, in the two main pathways of BA synthesis. Because females are more susceptible to BA related diseases, such as intrahepatic cholestasis of pregnancy, we expanded this model into female mice. The null mice of Cyp7a1 and Cyp27a1 were crossbred to create double knockout (DKO) mice. BA concentrations in female DKO mice had reductions in serum (63%), liver (83%), gallbladder (94%), and small intestine (85%), as compared to WT mice. Despite low BA levels, DKO mice had a similar expression pattern to that of WT mice for genes involved in BA regulation, synthesis, conjugation, and transport. Additionally, through treatment with a synthetic FXR agonist, GW4064, female DKO mice responded to FXR activation similarly to WT mice.

Advances in metabolic engineering for vitamins production

Vitamins are organic substances that are essential for the maintenance of life activities. Generally, vitamins need to be obtained from the diet or from some synthetic source as the body cannot synthesize vitamins, or the amounts of the synthesized vitamins are insufficient. At present, vitamins are widely used in medicine, food additives, feed additives, cosmetics and other fields, and the global demand for vitamins is constantly growing. Vitamins can be produced from chemical or microbial synthesis. Chemical synthesis usually requires harsh reaction conditions, produces serious wastes, and creates great potential safety hazard. In contrast, microbial synthesis of vitamins is greener, safer, and requires much less energy input. This review summarizes the advances in metabolic engineering for vitamins production in the past 30 years, with a focus on production of water-soluble vitamins (vitamins B1, B2, B3, B5, B6, B7, B9, B12 and vitamin C precursors) and lipid-soluble vitamins (vitamin A, precursors of vitamin D, vitamin E and vitamin K). Moreover, the bottlenecks for fermentative production of vitamins are discussed, and future perspectives for developing next generation vitamins producing strains using synthetic biotechnology are prospected.

A Low Vitamin A Diet Decreases Skeletal Muscle Performance

Vitamin A (retinol) is an essential lipid-soluble vitamin important for a number of biological functions. In mice, reduction of its dietary content by substituting standard rodent chow with a chow containing 5 times less vitamin A and feeding mice for two generations with this modified diet, results in the depletion of all-trans- retinoic acid. In the present study we investigated if the low vitamin A diet affects skeletal muscle function. Mice fed the low vitamin A diet ran significantly less and at a slower speed compared to age matched chow fed mice.

Association Between ApoE Status, Circulating Vitamin A and Vitamin E Levels with Dyslipidemia in Aging Adults

The influence of ApoE or lipid-soluble vitamins on lipid profile has been well documented. However, the association between ApoE status, vitamin A (VA) and vitamin E (VE) with dyslipidemia has been seldom reported. The aim of the present study was to investigate the impact of ApoE status on circulating VA and VE in aging adults with dyslipidemia. A total of 1754 Chinese aged 55-75 was recruited from community health centers. They were interviewed to obtain demographic information. Food frequency questionnaire (FFQ) was used to investigate daily food intakes of the participants. Fasting venous blood samples were taken and used for serum lipid profile measurement and ApoE genotyping. Serum VA and VE concentrations were determined by using high-performance liquid chromatography (HPLC). Serum VE and VA concentrations were circulating lipids and ApoE status dependent. Dyslipidemia subjects showed higher serum TC, TG, HDL-c/LDL-c ratio, VE and lipid-adjusted VE levels than normal subjects. ApoE genotype-dependent differences in serum lipid profile, VE and VA levels were observed in both normal and dyslipidemia subjects. The relationship between circulating VA with dyslipidemia is modifiable by lipid status. Higher serum VE and lipid adjusted VE levels associated with increased risk of dyslipidemia in aging Chinese adults, especially in ApoE4 carriers. Large scale longitudinal study is required to determine the optimal circulating VE levels in the elderly based on different lipid profiles and ApoE status.

Systemic metabolite profiling reveals sexual dimorphism of AIBP control of metabolism in mice.

Emerging studies indicate that APOA-I binding protein (AIBP) is a secreted protein and functions extracellularly to promote cellular cholesterol efflux, thereby disrupting lipid rafts on the plasma membrane. AIBP is also present in the mitochondria and acts as an epimerase, facilitating the repair of dysfunctional hydrated NAD(P)H, known as NAD(P)H(X). Importantly, AIBP deficiency contributes to lethal neurometabolic disorder, reminiscent of the Leigh syndrome in humans. Whereas cyclic NADPHX production is proposed to be the underlying cause, we hypothesize that an unbiased metabolic profiling may: 1) reveal new clues for the lethality, e.g., changes of mitochondrial metabolites., and 2) identify metabolites associated with new AIBP functions. To this end, we performed unbiased and profound metabolic studies of plasma obtained from adult AIBP knockout mice and control littermates of both genders. Our systemic metabolite profiling, encompassing 9 super pathways, identified a total of 640 compounds. Our studies demonstrate a surprising sexual dimorphism of metabolites affected by AIBP deletion, with more statistically significant changes in the AIBP knockout female vs male when compared with the corresponding controls. AIBP knockout trends to reduce cholesterol but increase the bile acid precursor 7-HOCA in female but not male. Complex lipids, phospholipids, sphingomyelin and plasmalogens were reduced, while monoacylglycerol, fatty acids and the lipid soluble vitamins E and carotene diol were elevated in AIBP knockout female but not male. NAD metabolites were not significantly different in AIBP knockout vs control mice but differed for male vs female mice. Metabolites associated with glycolysis and the Krebs cycle were unchanged by AIBP knockout. Importantly, polyamine spermidine, critical for many cellular functions including cerebral cortex synapses, was reduced in male but not female AIBP knockout. This is the first report of a systemic metabolite profile of plasma samples from AIBP knockout mice, and provides a metabolic basis for future studies of AIBP regulation of cellular metabolism and the pathophysiological presentation of AIBP deficiency in patients.

Vitamin D Deficiency in the Elderly Patients and Role of Vitamin D in the Prevention of COVID-19 Infection

SARS Covid'19 is declared as a global pandemic by World Health Organization [1]. The aim of this short report is to find out the association of Vitamin D in prevention of Covid'19 in elderly patients who are already having other co-morbidities. People of any age are susceptible to Corona virus but the elderly patients and patients with chronic underlying diseases are at higher risk. Many elderly patients with COVID-19 are at risk of mal-nutrition [2].&#x0D; Vitamins are of two types, Lipid soluble vitamins and water-soluble vitamins [3]. Lipid soluble vitamins can be stored in the body while water soluble vitamins cannot be stored in the body, hence needed to take regularly [4]. Vitamin D is a lipid soluble vitamin also it can be synthesized by our own body.

CFTR Modulator Therapy with Lumacaftor/Ivacaftor Alters Plasma Concentrations of Lipid-Soluble Vitamins A and E in Patients with Cystic Fibrosis.

Rationale: Cystic fibrosis (CF), caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, leads to impaired pancreatic function and therefore reduced intestinal absorption of lipids and fat-soluble vitamins especially in patients with CF developing pancreatic insufficiency (PI). Previous studies showed that CFTR modulator therapy with lumacaftor-ivacaftor (LUM/IVA) in Phe508del-homozygous patients with CF results in improvement of pulmonary disease and thriving. However, the effects of LUM/IVA on plasma concentration of the lipid soluble vitamins A and E remain unknown. Objectives: To investigate the course of plasma vitamin A and E in patients with CF under LUM/IVA therapy. Methods: Data from annual follow-up examinations of patients with CF were obtained to assess clinical outcomes including pulmonary function status, body mass index (BMI), and clinical chemistry as well as fat-soluble vitamins in Phe508del-homozygous CF patients before initiation and during LUM/IVA therapy. Results: Patients with CF receiving LUM/IVA improved substantially, including improvement in pulmonary inflammation, associated with a decrease in blood immunoglobulin G (IgG) from 9.4 to 8.2 g/L after two years (p < 0.001). During the same time, plasma vitamin A increased significantly from 1.2 to 1.6 µmol/L (p < 0.05), however, levels above the upper limit of normal were not detected in any of the patients. In contrast, plasma vitamin E as vitamin E/cholesterol ratio decreased moderately over the same time from 6.2 to 5.5 µmol/L (p < 0.01). Conclusions: CFTR modulator therapy with LUM/IVA alters concentrations of vitamins A and vitamin E in plasma. The increase of vitamin A must be monitored critically to avoid hypervitaminosis A in patients with CF.

Polyunsaturated \u03c9-3 fatty acids inhibit ACE2-controlled SARS-CoV-2 binding and cellular entry

The strain SARS-CoV-2, newly emerged in late 2019, has been identified as the cause of COVID-19 and the pandemic declared by WHO in early 2020. Although lipids have been shown to possess antiviral efficacy, little is currently known about lipid compounds with anti-SARS-CoV-2 binding and entry properties. To address this issue, we screened, overall, 17 polyunsaturated fatty acids, monounsaturated fatty acids and saturated fatty acids, as wells as lipid-soluble vitamins. In performing target-based ligand screening utilizing the RBD-SARS-CoV-2 sequence, we observed that polyunsaturated fatty acids most effectively interfere with binding to hACE2, the receptor for SARS-CoV-2. Using a spike protein pseudo-virus, we also found that linolenic acid and eicosapentaenoic acid significantly block the entry of SARS-CoV-2. In addition, eicosapentaenoic acid showed higher efficacy than linolenic acid in reducing activity of TMPRSS2 and cathepsin L proteases, but neither of the fatty acids affected their expression at the protein level. Also, neither reduction of hACE2 activity nor binding to the hACE2 receptor upon treatment with these two fatty acids was observed. Although further in vivo experiments are warranted to validate the current findings, our study provides a new insight into the role of lipids as antiviral compounds against the SARS-CoV-2 strain.

Cholesterol Pushes Vitamin E and Polyunsaturated Phospholipids Together

Vitamin E (α-tocopherol) is an essential micronutrient that protects membrane lipids from oxidative damage. Whether this lipid-soluble vitamin preferentially locates in the vicinity of polyunsaturated phospholipids that are most vulnerable to oxidation continues to be debated. We apply MD simulations to address this issue. A key role for cholesterol, ubiquitous in mammalian membranes, is revealed. Binding energies measured for vitamin E in all-atom (AA) umbrella sampling simulations are lower for polyunsaturated phospholipids than less unsaturated phospholipids - they do not indicate preferential interaction with polyunsaturated phospholipids. There is a reduction in the binding energy following the introduction of cholesterol, which we suggest drives vitamin E and polyunsaturated phospholipids together. Support is provided by largescale simulations performed over an extended timescale on vitamin E in mixtures of PDPC (1-palmitoyl-2-docosahexaenoylphosphatidylcholine) with SM (sphingomyelin) and cholesterol that separate into a (raft-like) domain enriched in SM and cholesterol (raft-like) and a (non-raft ) region composed primarily of PDPC (non-raft) but depleted in cholesterol. In coarse-grained (CG) and AA simulations vitamin E is excluded from the raft-like domain and thereby placed in closer proximity to polyunsaturated phospholipids. We surmise that the much greater abundance of cholesterol, which has high affinity for saturated SM, relative to vitamin E is responsible.

Completion of the gut microbial epi-bile acid pathway

ABSTRACT Bile acids are detergent molecules that solubilize dietary lipids and lipid-soluble vitamins. Humans synthesize bile acids with α-orientation hydroxyl groups which can be biotransformed by gut microbiota to toxic, hydrophobic bile acids, such as deoxycholic acid (DCA). Gut microbiota can also convert hydroxyl groups from the α-orientation through an oxo-intermediate to the β-orientation, resulting in more hydrophilic, less toxic bile acids. This interconversion is catalyzed by regio- (C-3 vs. C-7) and stereospecific (α vs. β) hydroxysteroid dehydrogenases (HSDHs). So far, genes encoding the urso- (7α-HSDH & 7β-HSDH) and iso- (3α-HSDH & 3β-HSDH) bile acid pathways have been described. Recently, multiple human gut clostridia were reported to encode 12α-HSDH, which interconverts DCA and 12-oxolithocholic acid (12-oxoLCA). 12β-HSDH completes the epi-bile acid pathway by converting 12-oxoLCA to the 12β-bile acid denoted epiDCA; however, a gene(s) encoding this enzyme has yet to be identified. We confirmed 12β-HSDH activity in cultures of Clostridium paraputrificum ATCC 25780. From six candidate C. paraputrificum ATCC 25780 oxidoreductase genes, we discovered the first gene (DR024_RS09610) encoding bile acid 12β-HSDH. Phylogenetic analysis revealed unforeseen diversity for 12β-HSDH, leading to validation of two additional bile acid 12β-HSDHs through a synthetic biology approach. By comparison to a previous phylogenetic analysis of 12α-HSDH, we identified the first potential C-12 epimerizing strains: Collinsella tanakaei YIT 12063 and Collinsella stercoris DSM 13279. A Hidden Markov Model search against human gut metagenomes located putative 12β-HSDH genes in about 30% of subjects within the cohorts analyzed, indicating this gene is relevant in the human gut microbiome.