Lipophilic Vitamin Research Articles

Ocular Drug Delivery through pHEMA-Hydrogel Contact Lenses Co-Loaded with Lipophilic Vitamins

Ocular drug delivery through hydrogel contact lenses has great potential for the treatment of ocular diseases. Previous studies showed that the loading of lipophilic vitamin E to silicone-hydrogel contact lenses was beneficial in ocular drug delivery. We hypothesized that vitamin E loading to another type of popular hydrogel contact lenses, pHEMA-hydrogel contact lenses, improves ocular drug delivery by increasing the drug loading or the duration of drug release. Loading of vitamin E to pHEMA-hydrogel contact lenses significantly increased the loading of a hydrophilic drug surrogate (Alexa Fluor 488 dye) and two hydrophilic glaucoma drugs (timolol and brimonidine) to the lenses by 37.5%, 19.1%, and 18.7%, respectively. However, the release duration time was not significantly altered. Next, we hypothesized that the lipophilic nature of vitamin E attributes to the enhanced drug loading. Therefore, we investigated the effects of co-loading of another lipophilic vitamin, vitamin A, on drug surrogate delivery. We found out that vitamin A loading also increased the loading of the drug surrogate to pHEMA-hydrogel contact lenses by 30.3%. Similar to vitamin E loading, vitamin A loading did not significantly alter the release duration time of the drug or drug surrogate.

The Lipophilic Vitamin C Derivative, 6-O-Palmitoylascorbate Protects Human Keratinocytes and 3D-Human Skin Equivalents Against X-Ray-Induced Oxidative Stress and Apoptosis More Markedly Than L-Ascorbic Acid.

The aim of this study was to investigate preventive effects of the lipophilic vitamin C derivative, 6-O-palmitoylascorbate (PlmtVC) against X-ray radiation-induced harmful events. Free radical scavenging activity tests showed that both fresh and old (being kept at 37°C for 72 h) solutions of PlmtVC showed significantly higher abilities for scavenging both DPPH and peroxyl radical (ROO·) radicals than L-ascorbic acid (L-AA) under the same conditions, suggesting that PlmtVC is an antioxidant more efficient and stable than L-AA. Irradiation with X-ray (15 Gy) increased intracellular ROS production, lipid peroxidation and protein carbonylation, in human keratinocytes HaCaT, all of which were repressed, especially for intracellular ROS more markedly, by PlmtVC than by L-AA. After X-ray (15 Gy)-irradiation, caspase 3/7 activation and TUNEL-detected DNA-strand-breakages characteristic of apoptosis obviously increased in HaCaT cells or 3D-skin tissue equivalents, respectively, both of which were prevented more appreciably by PlmtVC than by L-AA. PlmtVC also noticeably prevented cumene hydroperoxide-induced generation of cellular ROS in epidermis parts of 3D-skin equivalents. Thus, PlmtVC prevents X-ray-induced diverse harmful effects, through its antioxidant activity and the palmitoyl moiety-based lipophilicity, more efficiently than L-AA. J. Cell. Biochem. 118: 318-329, 2017. © 2016 Wiley Periodicals, Inc.

Morphological stability of microencapsulated vitamin formulations by AFM imaging

Abstract The morphological stability of microencapsulated lipophilic vitamin formulations directly influences the long-term storage stability and performance in final applications. The internal particle morphology of three commercial dry Vitamin A acetate formulations differing in their matrix composition (hydrocolloid/polysaccharide and plasticizer) was systematically characterized by atomic force microscopy (AFM). The evolution of the particle internal morphology after per-se storage at 25 and 40 °C for ten months was investigated. Furthermore, an accelerated stress test by in-situ heating and AFM imaging was developed. Surface roughness parameters from the AFM images were used to semi-quantitatively estimate the evolution of the particle internal microstructure, and thus the aging and destabilization of the lipophilic vitamin formulations. The influence of humidity level on the thermal morphological restructuring of one of the commercial samples was also investigated. This study has shown that such AFM investigations of microparticles are a novel analytical tool to rapidly estimate the physical stability of the lipophilic vitamin dried emulsions.

Low Vitamin D Levels Do Not Predict Hyperglycemia in Elderly Endurance Athletes (but in Controls).

Background and AimRecent studies revealed a link between hypovitaminosis D3 and the risk for hyperglycemia. Further mechanistic and interventional investigations suggested a common reason for both conditions rather than a causal relationship. Exposure to sunlight is the most relevant source of vitamin D3 (25(OH)D), whereas adipose tissue is able to store relevant amounts of the lipophilic vitamin. Since running/bicycling leads to increased out-door time and alters physiological response mechanisms, it can be hypothesized that the correlation between hypovitaminosis D3 and hyperglycemia might be disturbed in outdoor athletes.Methods47 elderly marathoners/bicyclists and 47 age/sex matched controls were studied in a longitudinal setting at baseline and after three years. HbA1c as a surrogate for (pre-)diabetic states was quantified via HPLC, 25(OH)D levels were measured by means of chemiluminescent assays. Physical performance was assessed by ergometry.ResultsWhen adjusted for seasonal variations, 25(OH)D was significantly higher in athletes than in controls. 25(OH)D levels inversely correlated with triglycerides in both groups, whereas only in controls an association between high BMI or low physical performance with hypovitaminosis D3 had been found. Likewise, the presence of hypovitaminosis D3 at baseline successfully predicted hyperglycemia at the follow up examinations within the control group (AUC = 0.85, 95% CI [0.74, 0.96], p < .001, statistically independent from BMI), but not in athletes.ConclusionOur data suggest that mechanisms of HbA1c elevation might differ between athletes and controls. Thus, intense physical activity must be taken into account as a potential pre-analytic confounder when it is aimed to predict metabolic risk by vitamin D3 levels.

Adsorptive stripping voltammetry in lipophilic vitamins determination

The aim of this contribution was to check if adsorptive stripping differential pulse voltammetry (AdSDPV) is suitable tool for sensitive simultenous electrochemical detection of lipophilic vitamins. Retinol (vitamin A1), cholecalciferol (vitamin D3), α-tocopherol (vitamin E) and phylloquinone (vitamin K1) were selected as representatives. All electrochemical measurements were performed in two separate steps due to the lipophilic character of the analytes. In the first step, an accumulation of lipophilic vitamin on the surface of glassy carbon electrode (GCE) was done by immersing working electrode into the aqueous”‘acetonitrile solutions (50%, v/v) of each vitamin (50.0 µmol.L-1) at 400 rpm for 5 min. In the second one, differential pulse voltammetry of accumulated vitamins was performed in 0.01 mol.L-1 acetate (pH 4.5) buffer at potential step (Estep) 5 mV, potential of amplitude (Eampl) 25 mV, interval time (t) 0.1 s and scan rate (ν) 50 mV.s-1. It was observed that electrochemical behaviour of lipophilic vitamins adsorbed on surface of solid GCE in the aqueous electrolyte was very similar to those performed in organic/aqueous electrolyte in literature. Due to reversible electrochemical behaviour of vitamin K1 (phylloquinone/phyllohydroquinone redox couple), it was possible to detect all lipophilic vitamins only in one analysis. Observed values of peak potentials (Ep) were sufficiently different for their recognition which was confirmed by the analysis of real sample. The results obtained in this study showed that simultaneous determination of some lipophilic vitamins is possible requiring further optimization study. For this reason, it is necessary to understand this work as an initial step in simultaneous determination of lipophilic vitamins without application of any chromatographic technique.

Efficacy of peptide nucleic acid and selected conjugates against specific cellular pathologies of amyotrophic lateral sclerosis

Cellular studies have been undertaken on a nonamer peptide nucleic acid (PNA) sequence, which binds to mRNA encoding superoxide dismutase 1, and a series of peptide nucleic acids conjugated to synthetic lipophilic vitamin analogs including a recently prepared menadione (vitamin K) analog. Reduction of both mutant superoxide dismutase 1 inclusion formation and endoplasmic reticulum stress, two of the key cellular pathological hallmarks in amyotrophic lateral sclerosis, by two of the prepared PNA oligomers is reported for the first time.

A tale of 2 cousins: An atypical and a typical case of abetalipoproteinemia

Abetalipoproteinemia (ABL) is a rare recessive genetic disease caused by mutations of the MTTP gene. This disease is characterised by a defect in the lipidation of APO B and the absence of VLDL and chylomicron production. Patients affected by ABL present neurological, hemalogical and gastro-intestinal symptoms due to deficiency in lipophilic vitamins and fat malabsorption. We herein report the case of two cousins, one presenting classical symptoms of abetalipoproteinemia and one presenting a much attenuated phenotype. The proband carried a novel combination of MTTP mutations, the 1867+1G>A and the R540C mutations. This patient never received any vitamin supplements and was relatively free of symptoms despite an undetectable APO B concentration. Her cousin was homozygous for 1867+1G>A MTTP mutation and presented most of the classical symptoms of ABL. In conclusion we report a very unusual kindred where on affected member is strongly symptomatic of ABL whereas the other presents very mostly asymptomatic disease suggesting that ABL can present itself with a very incomplete clinical penetrance.

Modulation of Gel Phase Model Membranes by Vitamin D-Related Proteins

Severe vitamin D deficiency has long been linked to dysfunctions of the musculoskeletal system, and more recent studies have also associated vitamin D deficiency with other conditions, ranging from certain cancers to cardiovascular disease and diabetes. Vitamin D is a steroidal hormone that can be biosynthesized from 7-dehydrocholesterol by the action of UV light on skin (vitamin D3 only), or obtained from dietary sources (vitamins D3 and D2). Vitamins D3 and D2 are inactive precursor molecules that must be successively hydroxylated in the kidney and liver in order to become active. The vitamin D binding protein (DBP, GC-globulin) is responsible for transporting the lipophilic vitamin D throughout the body, and the vitamin D receptor (VDR) is the transcription factor that exerts the most well-established activities of vitamin D in the cell nucleus. Here, we present data based on synchrotron X-ray diffraction, 31P NMR and 2H NMR describing the effects of DBP and VDR in modulating the phase behavior of model membranes composed of DPPC, brain-sphingomyelin and cholesterol. Initial results suggest that DBP particularly interacts with the bilayers to reduce the gel-fluid lamellar phase transition and increase lipid mixing in ternary membranes, with the effect of VDR being somewhat less significant. These data have consequences for our understanding of how the action of soluble proteins that bind lipophilic, membrane-based molecules may alter bilayer structure and dynamics as they interact with the membrane surface to identify and extract their target.

Determination of antioxidant and antimicrobial properties of Eremurus spectabilis Bieb.

In this study, in vitro antioxidant and antimicrobial activities of the E. spectabilis Bieb., which is consumed as a vegetable among people, was investigated and Kluyveromyces lactis ’s antioxidant activies in anaerobic cultural environment is researched. This purpose; 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity, flavonoid, resveratrol, sugar contents, lipid peroxidation (LPO) levels, fatty acid level, lipophilic vitamin values, protein and glutathione amounts were measured. In the FeCl group in which FeCl 2 + H 2 O 2 is applied, when compared with LPO level control group (K), it was observed that it increase in high amount (p<0.05). LPO level decreases in certain proportions in treatment groups. It is suggested that the lowering effect of the LPO of E. spectabilis extracts are arise from phytochemical like flavonoids that it includes. As a result of the antibacterial activity studies, it was observed that E. spectabilis have different proportional antimicrobial activities against E. coli, S. aureus, Epidermophyton spp. and C. albicans .

Dietary Vitamin K Intake Is Associated with Cognition and Behaviour among Geriatric Patients: The CLIP Study.

Our objective was to determine whether dietary vitamin K intake was associated with cognition and behavior among older adults. 192 consecutive participants ≥65 years, recruited in the cross-sectional CLIP (Cognition and LIPophilic vitamins) study, were separated into two groups according to the tertiles of dietary phylloquinone intake (i.e., lowest third below 207 µg/day versus the other two thirds combined). Daily dietary phylloquinone intake was estimated from 50-item interviewer-administered food frequency questionnaire. Cognition was assessed with Mini-Mental State Examination (MMSE); behaviour with Frontotemporal Behavioral Rating Scale (FBRS). Age, gender, social problems, education, body mass index (BMI), comorbidities, history of stroke, use vitamin K antagonists, inadequate fatty fish intake, serum thyroid-stimulating hormone (TSH), vitamin B12, albumin, and estimated glomerular filtration rate were used as confounders. Compared to participants in the lowest third of dietary phylloquinone intake (n = 64), those with higher intake had higher (i.e., better) mean MMSE score (22.0 ± 5.7 versus 19.9 ± 6.2, p = 0.024) and lower (i.e., better) FBRS score (1.5 ± 1.2 versus 1.9 ± 1.3, p = 0.042). In multivariate linear regressions, log dietary phylloquinone intake was positively associated with MMSE score (adjusted β = 1.66, p = 0.013) and inversely associated with FBRS score (adjusted β = −0.33, p = 0.037). Specifically, log dietary phylloquinone intake correlated negatively with FBRS subscore of physical neglect (r = −0.24, p = 0.001). Higher dietary phylloquinone intake was associated with better cognition and behavior among older adults.

Interspecies and seasonal differences of retinol in dairy ruminant´s milk

Milk is an essential source of macronutrients and among lipophilic vitamins is significant source of retinol. The contribution of milk to the reference daily intake for retinol varies from 11% to 16%, worldwide. The most consumed dairy products are fresh, dehydrated and condensed milk in which the amonuts of retinol are not modified to those of in whole milk. Retinol is essential to ensure a good functionality of the immune system and plays a critical role in vision, reproduction, cell differentiation as well as growth and development and is found only in animal tissues. The aim of our study was to evaluate the interspecies differences in the retinol concentration of whole raw bovine, caprine and ovine milk and to observe seasonal variation of retinol in bulk tank milk samples. Samples of raw milk were colleceted on different farms in the Czech Republic between 2013 and 2014. Retinol was measured by ultra high performance liquid chromatography with UV detection (325 nm) in isocratic mode after alkaline saponification with methanolic potassium hydroxide solution and liquid-liquid extraction into non polar organic solvent of whole raw milk. To avoid vitamin losses or degradation during the procedure, antioxidants were added to the sample extraction media. Our results indicate significant interspecies differences between bovine and ovine milk and caprine and ovine milk. Concentration of retinol is very similar in bovine and caprine milk 0.96 ±0.11 mg/L, 0.94 ±0.25 mg/L, respectively. The mean concentration in sheep´s milk is 1.75 ±0.24 mg/L. The seasonal variation of retinol in raw bovine milk was detected as high significant, with the highest concentration during winter. These results contribute to the nutrition evaluation of milk in the Czech Republic and indicate, that the sheep´s milk is the best source of retinol among the milks of ruminants kept in the Czech Republic, however it is not used in its fluid form for human consumption.

The effects of Juglans regia L. (walnut) extract on certain biochemical paramaters and in the prevention of tissue damage in brain, kidney, and liver in CCl4 applied Wistar rats

Abstract Objective: The purpose of this study is to demonstrate protective effects of walnut samples on CCl4- induced tissue damage in vivo. Methods: Walnut fruits were extracted and then subjected to vitamin and flavonoid analyses. The extracts obtained were injected intraperitoneally every other day to Wistar male rats given carbon tetrachloride (CCl4) and the animals were decapitated at the end of the study period. The brain, kidney, and liver tissues were removed and lipid peroxidation (LPO) measurements were done in the lipid fraction generated. The fatty acids in the lipid extract were analyzed by gas chromatography after converting them into methyl esters. In addition, the amounts of glutathione, protein, and vitamins were analyzed. Results: Given the results achieved, it was found that the levels of fatty acids increased in the brain and kidney tissues after CCl4 administration (p&lt;0.001). In the groups given walnut extract against CCl4, it was found that the glutathione (GSH) level increased and malondialdehyde (MDA) level reduced in all tissues (p&lt;0.05, p&lt;0.01). Given lipophilic vitamin levels, it was found that α-tocopherol level increased in the brain and liver tissues in the group receiving additional walnut in comparison with the controls (p&lt;0.05), and cholesterol level increased in the tissues, except kidney, in all groups in comparison with the control group (p&lt;0.05, p&lt;0.001). Conclusion: Our data indicates that walnut extract has protective effects against LPO formation in the brain, kidney and liver tissues.

Secreted phospholipase A2 inhibitor modulates fatty acid composition and reduces obesity-induced inflammation in Beagle dogs

Secreted phospholipase A2 inhibitor (sPLA2i) has been reported to have an anti-inflammatory function by blocking the production of inflammatory mediators. Obesity is characterized by low-grade inflammation and oxidative stress. The aim of this study was to investigate the effects of dietary supplementation of sPLA2i on inflammation, oxidative stress and serum fatty acid profile in dogs. Seven obese and seven lean Beagle dogs were used in a 28-day double blind cross-over design. Dogs were fed a control diet without supplemental sPLA2i or an sPLA2i supplemented diet.The sPLA2i diet decreased plasma fibrinogen levels and increased the protein:fibrinogen ratio in obese dogs to levels similar to those of lean dogs fed the same diet. Obese dogs had a higher plasma concentration of the lipophilic vitamin A with potential antioxidative capacity and a lower ratio of retinol binding protein 4:vitamin A compared to lean dogs, independent of the diets. A higher proportion of myristic acid (C14:0) and a lower proportion of linoleic acid (C18:2n-6) were observed in the dogs fed with the sPLA2i diet compared to dogs fed with the control diet. Furthermore, a higher ratio of n-6 to n-3, a lower proportion of n-3 polyunsaturated fatty acids and lower omega-3 index were observed in obese compared to lean dogs. The results indicate that obese dogs are characterized by a more ‘proinflammatory’ serum fatty acid profile and that diet inclusion of sPLA2i may reduce inflammation and alter fatty acid profile.

Factors influencing the content of vitamins A and E in sheep and goat milk

The content of lipophilic vitamins A and E was determined in samples of sheep and goat milk of different breeds coming from 9 farms in central, eastern, and southern Bohemia. Samples were collected throughout the period of lactation (from April to September). Vitamins A and E were determined by HPLC using DAD and FLD detectors. Vitamin A was determined in all samples but only α-tocopherol (out of various forms of vitamin E) was detected in all samples. The total average content of vitamins A and E in raw milk of all sheep breeds during lactation was 0.93 ± 0.07 and 2.93 ± 0.87 mg/kg, levels of these vitamins in goat milk were 0.79 ± 0.08 and 1.29 ± 0.35 mg/kg, respectively. The results showed a significantly medium and strong correlation between the content of vitamin A and E and the content of fat (R2 = 0.57 and 0.75, respectively). The year did not have any statistically significant influence on the content of monitored vitamins. The content of both vitamins is dependent on the phase of lactation. The levels of vitamins A and E were significantly lower in the early phase and significantly higher in the late phase of lactation. The amount of monitored vitamins slightly decreased during pasteurisation. A strong decrease in the content of both vitamins was observed during the first two weeks after milk storage in a freezing box at the temperature of -20°C (about 11-55%).

Biology of subjective cognitive complaint amongst geriatric patients: vitamin D involvement.

Insufficiency in vitamin D, a neurosteroid hormone, is associated with cognitive decline in older adults. The impact on the subjective perception of cognitive decline has not yet been examined. The objective of this cross-sectional hospital-based study was to determine whether vitamin D insufficiency was associated with subjective cognitive complaint amongst geriatric patients. Ninety-nine consecutive Caucasian in- and outpatients recruited in the 'Cognition and LIPophilic vitamins' (CLIP) study, who had no advanced cognitive disorders (i.e., Mini-Mental State Examination score≥20) and who took no vitamin D supplements, were categorized into 2 groups based on vitamin D insufficiency (i.e., serum 25-hydroxyvitamin D≥75 nmol/L). Subjective cognitive complaint was examined using the Memory Complaint Questionnaire (MAC-Q; score 0-30, best). MAC-Q score<15 out of 30 defined severe cognitive complaint. Age, gender, body mass index, education level, comorbidity burden, functional autonomy, mood, and serum concentrations of parathyroid hormone, calcium, thyroid-stimulating hormone and vitamin B12, and estimated glomerular filtration rate were used as potential confounders. Compared to participants with serum 25OHD>75 nmol/L, those with vitamin D insufficiency (n=89) had a lower mean MAC-Q score (14.9±2.9 versus 17.1±1.6, P=0.02) and more often a MAC-Q score<15 (52.8% versus 10.0%, P=0.01). Vitamin D insufficiency was inversely associated with the MAC-Q score (adjusted β=-2.84, P=0.03), and positively associated with severe cognitive complaint (adjusted OR=10.07, P=0.03). Vitamin D insufficiency was associated with subjective cognitive complaint in the studied cohort of geriatric patients.

The relationships of high-fat diet and metabolism of lipophilic vitamins

Obesity has become a worldwide problem. One dietary style contributing to this epidemic is the Western diet or high-fat diet (HFD), which is marked by its high-fat content. The effects of HFD on the development of chronic metabolic diseases, such as obesity, have been observed in both human and animal studies. Consumption of HFD generally causes increase of body fat mass with development of symptoms of metabolic diseases such as hyperlipidemia and insulin resistance. Micronutrients are essential for the general health of an individual. Their needs are satisfied by dietary intake. Digestion, absorption and transport of dietary lipophilic vitamins share similar pathways as that of dietary fats. It is still unclear how amounts and compositions of dietary fats affect digestion, absorption and function of lipophilic vitamins and vice versa. A better understanding of the impacts of HFD on homeostasis and functions of lipophilic vitamins may shed light on the development mechanisms of obesity and other metabolic diseases. This review aims to investigate the impact of high-fat feeding on functions of lipophilic vitamins. Research included in this review ranges in publication year 1995 to 2014. It seems that the link between fat metabolism and lipophilic vitamin metabolism has started to be recognized. Additional research projects are warranted.

Characterization of partitioning behavior of vitamins in micellar systems using affinity capillary electrophoresis

Introduction: Micellar Electrokinetic Chromatography, sometimes referred as Affinity Capillary Electrophoresis, is a useful tool to the characterization of the drug partitioning in different vehicle systems such as micelles and microemulsions using the capacity factor as hydrophobicity parameter. Bile acids, because of their important role in biological systems, are applied widely in ACE method to characterization of partition properties of solutes. In this paper the interaction of some hydrophilic and lipophilic vitamins with micellar systems consisted of bile salts and phospholipids was considered using ACE. Material and Methods: Three mixed micelles and one microemulsion were employed. The samples were filtered through a 0.45 μm filter. 13 vitamins, consist of 4 lipophilic and 9 hydrophilic vitamins were investigated. Each vitamin was solved in different micellar systems (0.1 mg/ml). Then, using ACE, the electropherogram of samples was obtained under certain run conditions. The capacity factor for each sample was calculated according the migration times in the electropherogram. DMSO and Sudan red were used as EOF tracer and micelle tracer respectively. All experiments were carried out with certain instrumental conditions. Results and Discussion: The results show that the migration times of lipophilic vitamins are equal to migration time of micellar tracer and consequently the capacity factor of all of them tends to infinity. In fact these vitamins, concerning the hydrocarbonic chain in their chemical structure, are incorporated in the inner oil core of mixed micelle or microemulsion and moved with it. Four hydrophilic vitamins (niacinamid, pyridoxine, D-panthenol and cyanocobalamin) have different affinity to Micellar systems. But for each vitamin the affinity to different system is almost same. K′ zero means that vitamin has not any affinity to micelle, remains in aqueous phase and moves with EOF. Five hydrophilic vitamins (ascorbic acid, folic acid, riboflavin, biotin and thiamin) had charged behavior. The electrophoretic mobility of all these vitamins was negative, except thiamin which has positive mobility. Two important parameters that may influence these migration behaviors of charged solutes are pH and micelle concentration. Distribution properties of molecules mostly change depending to pH value of the media because of the effect of pH on the chemical interaction. In the other hand, it might be that the negative charge of bile salt's micelle increases by mixing with phospholipids, and causes to stronger repulsion between negative charged micelle and anion analyte. So the electrophoretic mobility of anionic vitamins in presence of micelle would be reduced. Conclusion: The MEKC technique as a method of ACE was employed to determination partitioning pattern of various kinds of vitamins in a micellar solutions. The affinity of both hydrophilic and lypophilic vitamins to micellar system was investigated by calculation the capacity factor. This value for lypophilic vitamins is infinite, because they incorporate with micelle compositions and moved with them. In contrast hydrophilic vitamins exhibited different partitioning behaviour in micellar solution. The negative value obtained for anionic hydrophilic vitamins can be corrected by change some condition like micellar concentration and the pH of media.

Food protein-based microspheres for increased uptake of vitamin D3

To protect vitamin D3 during cold storage and exposure to UV-light, vitamin D3 has been entrapped in microspheres formed by bovine protein β-lactoglobulin (βlg) and lysozyme (Lyso) from egg white. The behaviour of the βlg/Lyso microspheres in simulated intestinal fluid and their impact on the kinetic release of D3 were determined. The impact of the D3-loaded βlg/Lyso microspheres on the bioavailability of D3 was evaluated in vivo by force-feeding rats. The data indicate that the βlg/Lyso microspheres effectively improved the stability of D3, which was readily released in the intestines. The release kinetics were accelerated in the presence of proteolytic enzymes. The bioavailability of D3 was improved, as confirmed by the significant increase in the serum levels of 25-hydroxy-D3 in rats. The current work demonstrates that water soluble proteins were used to substantially increase the bioavailability of the lipophilic vitamin, and thus can serve in the oral delivery of D3.

STRA6 is critical for cellular vitamin A uptake and homeostasis.

Vitamin A must be adequately distributed within the body to maintain the functions of retinoids in the periphery and chromophore production in the eyes. Blood transport of the lipophilic vitamin is mediated by the retinol-binding protein, RBP4. Biochemical evidence suggests that cellular uptake of vitamin A from RBP4 is facilitated by a membrane receptor. This receptor, identified as the Stimulated by retinoic acid gene 6 (Stra6) gene product, is highly expressed in epithelia that constitute blood-tissue barriers. Here we established a Stra6 knockout mouse model to analyze the metabolic basis of vitamin A homeostasis in peripheral tissues. These mice were viable when bred on diets replete in vitamin A, but evidenced markedly reduced levels of ocular retinoids. Ophthalmic imaging and histology revealed malformations in the choroid and retinal pigmented epithelium, early cone photoreceptor cell death, and reduced lengths of rod outer segments. Similar to the blood-retina barrier in the RPE, vitamin A transport through the blood-cerebrospinal fluid barrier in the brain's choroid plexus was impaired. Notably, treatment with pharmacological doses of vitamin A restored vitamin A transport across these barriers and rescued the vision of Stra6(-/-) mice. Furthermore, under conditions mimicking vitamin A excess and deficiency, our analyses revealed that STRA6-mediated vitamin A uptake is a regulated process mandatory for ocular vitamin A uptake when RBP4 constitutes the only transport mode in vitamin A deficiency. These findings identifying STRA6 as a bona fide vitamin A transporter have important implications for disease states associated with impaired blood vitamin A homeostasis.

Lipid Metabolism During Pregnancy and its Implications for Fetal Growth

More glucose crosses the placenta than any other substrate, but correlations between its concentration in maternal plasma and fetal growth are not found consistently. The accumulation of maternal fat depots and hyperlipidemia are the two principal changes in lipid metabolism during pregnancy. Although lipids cross the placenta with difficulty, maternal plasma triacylglycerols (TAG) and non-esterified fatty acids (NEFA) correlate with fetal lipids, fetal growth and fat mass under certain conditions. In intrauterine growth restriction, impaired placental transfer of lipophilic compounds (long-chain polyunsaturated fatty acids and lipophilic vitamins) seems to underpin metabolic dysfunction and decreased birth weight. In gestational diabetes mellitus (GDM), maternal TAG and NEFA levels correlate with neonatal anthropometric measures. In GDM, adipocyte fatty acid-binding protein in fetuses correlated with neonatal fat mass; changes in maternal or cord blood leptin, retinol binding protein 4 and adiponectin concentrations have been related to neonatal fat mass or birth weight, although their importance remains to be investigated. The angiopoietin-like protein 4 (ANGPTL-4) is secreted from adipose tissue, liver and placenta, and irreversibly inhibits lipoprotein lipase (LPL) activity. Maternal plasma ANGPTL-4 is decreased in GDM, and it has been proposed to be responsible for an increase in placental LPL activity, which would facilitate a greater fatty acid placental transfer, contributing to the higher fetal fat accumulation. Thus, while evidence suggesting major involvement of maternal lipid metabolism in fetal adiposity and growth exists, the precise mechanisms remain to be elucidated.