Metabolism Of Fat-soluble Vitamins Research Articles

Mass-spectrometric analysis of APOB polymorphism rs1042031 (G/T) and its influence on serum proteome of coronary artery disease patients: genetic-derived proteomics consequences.

Genetic polymorphisms of apolipoprotein B gene (APOB) may result into serum proteomic perturbance in Coronary Artery Disease (CAD). The current case-control cohort of Pakistani subjects was designed to analyze the genetic influence of APOB rs1042031, (G/T) genotype on serum proteome. Subjects were categorized into two groups: CAD patients (n = 480) and healthy individuals (n = 220). For genotyping, tetra ARMS-PCR was carried out and validated through sequencing, whereas LC/MS-based proteomic analysis of serum samples was performed through label-free quantification. In initial step of genotyping, the frequencies of each genotype GG, GT, and TT were 70%, 27%, and 30% in CAD patients, while in control group, the subjects were 52%, 43%, and 5%, respectively, in CAD patients. The genotypic frequencies in patients vs. control groups found significantly different (p = 0.004), and a strong association of dominant alleles GG with the CAD was observed in both dominant (OR: 2.4 (1.71-3.34), p = 0.001) and allelic genetic models (OR: 2.0 (1.45-2.86), p = 0.001). In second step of label-free quantitation, a total of 40 significant proteins were found with altered expression in CAD patients. The enriched Gene Ontology (GO) terms of molecular functions and pathways of these protein showed upregulated pathways as follows: chylomicron remodeling and assembly, complement cascade activation, plasma lipoprotein assembly, apolipoprotein-A receptor binding, and metabolism of fat-soluble vitamins in G allele carrier of rs1042031 (G > T) vs. mutant T-allele carriers. This study provides better understanding of CAD pathobiology by proteogenomics of APOB. It evidences the influence of APOB rs1042031-dominant (GG) genotype with CAD patients.

Genetic Networks of Alzheimer's Disease, Aging, and Longevity in Humans.

Human genomic analysis and genome-wide association studies (GWAS) have identified genes that are risk factors for early and late-onset Alzheimer's disease (AD genes). Although the genetics of aging and longevity have been extensively studied, previous studies have focused on a specific set of genes that have been shown to contribute to or are a risk factor for AD. Thus, the connections among the genes involved in AD, aging, and longevity are not well understood. Here, we identified the genetic interaction networks (referred to as pathways) of aging and longevity within the context of AD by using a gene set enrichment analysis by Reactome that cross-references more than 100 bioinformatic databases to allow interpretation of the biological functions of gene sets through a wide variety of gene networks. We validated the pathways with a threshold of p-value < 1.00 × 10-5 using the databases to extract lists of 356 AD genes, 307 aging-related (AR) genes, and 357 longevity genes. There was a broad range of biological pathways involved in AR and longevity genes shared with AD genes. AR genes identified 261 pathways within the threshold of p < 1.00 × 10-5, of which 26 pathways (10% of AR gene pathways) were further identified by overlapping genes among AD and AR genes. The overlapped pathways included gene expression (p = 4.05 × 10-11) including ApoE, SOD2, TP53, and TGFB1 (p = 2.84 × 10-10); protein metabolism and SUMOylation, including E3 ligases and target proteins (p = 1.08 × 10-7); ERBB4 signal transduction (p = 2.69 × 10-6); the immune system, including IL-3 and IL-13 (p = 3.83 × 10-6); programmed cell death (p = 4.36 × 10-6); and platelet degranulation (p = 8.16 × 10-6), among others. Longevity genes identified 49 pathways within the threshold, of which 12 pathways (24% of longevity gene pathways) were further identified by overlapping genes among AD and longevity genes. They include the immune system, including IL-3 and IL-13 (p = 7.64 × 10-8), plasma lipoprotein assembly, remodeling and clearance (p < 4.02 × 10-6), and the metabolism of fat-soluble vitamins (p = 1.96 × 10-5). Thus, this study provides shared genetic hallmarks of aging, longevity, and AD backed up by statistical significance. We discuss the significant genes involved in these pathways, including TP53, FOXO, SUMOylation, IL4, IL6, APOE, and CEPT, and suggest that mapping the gene network pathways provide a useful basis for further medical research on AD and healthy aging.

Quantitative Proteomics Analysis of Berberine-Treated Colon Cancer Cells Reveals Potential Therapy Targets.

Simple SummaryColon cancer is one of the most common malignant tumors and beberine has been found to exert potential anti-colon cancer activity in vitro and in vivo. In this study, by using proteomics and bioinformatics approaches, we report that berberine may inhibit the proliferation of colon cancer cells by regulating mitochondrial translation and ribosome biogenesis, as well as by promoting calcium mobilization and metabolism of fat-soluble vitamins. Moreover, GTPase ERAL1 and mitochondrial ribosomal proteins MRPL11, 15, 30, 37, 40, and 52 have great potential to serve as potential therapeutic targets for colon cancer treatment.Colon cancer is one of the most lethal malignancies worldwide. Berberine has been found to exert potential anti-colon cancer activity in vitro and in vivo, although the detailed regulatory mechanism is still unclear. This study aims to identify the underlying crucial proteins and regulatory networks associated with berberine treatment of colon cancer by using proteomics as well as publicly available transcriptomics and tissue array data. Proteome profiling of berberine-treated colon cancer cells demonstrated that among 5130 identified proteins, the expression of 865 and 675 proteins were changed in berberine-treated HCT116 and DLD1 cells, respectively. Moreover, 54 differently expressed proteins that overlapped in both cell lines were mainly involved in mitochondrial protein synthesis, calcium mobilization, and metabolism of fat-soluble vitamins. Finally, GTPase ERAL1 and mitochondrial ribosomal proteins including MRPL11, 15, 30, 37, 40, and 52 were identified as hub proteins of berberine-treated colon cancer cells. These proteins have higher transcriptional and translational levels in colon tumor samples than that of colon normal samples, and were significantly down-regulated in berberine-treated colon cancer cells. Genetic dependency analysis showed that silencing the gene expression of seven hub proteins could inhibit the proliferation of colon cancer cells. This study sheds a light for elucidating the berberine-related regulatory signaling pathways in colon cancer, and suggests that ERAL1 and several mitochondrial ribosomal proteins might be promising therapeutic targets for colon cancer.

Widespread basal cytochrome P450 expression in extrahepatic bovine tissues and isolated cells

Periparturient cattle face increased risk of both metabolic and infectious diseases. Factors contributing to this predisposition include oxidized polyunsaturated fatty acids, also known as oxylipids, whose production is altered during the periparturient period and in diseased cattle. Alterations in the production of oxylipids derived from cytochrome P450 (CYP450) enzymes are over-represented during times of increased disease risk and clinical disease, such as mastitis. Many of these same CYP450 enzymes additionally regulate metabolism of fat-soluble vitamins, such as A, D, and E. These vitamins are essential to maintaining immune health, yet circulating concentrations are diminished near calving. Despite this, a relatively small amount of research has focused on the roles of CYP450 enzymes outside of the liver. The aim of this paper is to describe the relative gene expression of 11 CYP450 in bovine tissues and common in vitro bovine cell models. Eight tissue samples were collected from 3 healthy dairy cows after euthanasia. In vitro samples included primary bovine aortic and mammary endothelial cells and immortalized bovine kidney and mammary epithelial cells. Quantitative real-time-PCR was carried out to assess basal transcript expression of CYP450 enzymes. Surprisingly, CYP450 mRNA was widely expressed in all tissue samples, with predominance in the liver. In vitro CYP450 expression was less robust, with several cell types lacking expression of specific CYP450 enzymes altogether. Overall, cell culture models did not reflect expression of tissue CYP450. However, when CYP450 were organized by activity, certain cell types consistently expressed specific functional groups. These data reveal the widespread expression of CYP450 in individual organs of healthy dairy cows. Widespread expression helps to explain previous evidence of significant changes in CYP450-mediated oxylipid production and fat-soluble vitamin metabolism in organ microenvironments during periods of oxidative stress or disease. As such, these data provide a foundation for targeted functional experiments aimed at understanding the activities of specific CYP450 and associated therapeutic potential during times of increased disease risk.

Hybrid radial basis function with firefly algorithm and simulated annealing for detection of high cholesterol through iris images

Cholesterol is a lipid (fat) produced by the liver and is required to build and maintain cell membranes. Cholesterol is also important for the metabolism of fat soluble vitamins. This important lipid is found in human blood. Excess cholesterol (high cholesterol) can cause health problems such as being a factor of coronary heart disease that responsible for the heart attacks, liver or kidney disease. Observation of iris pattern can detect several types of diseases, one of which is high cholesterol. The purpose of this research is to detect whether someone is exposed to high cholesterol or not, through iris images based on firefly algorithm, simulated annealing, and radial basis function. Firefly algorithm and simulated annealing are used in the unsupervised learning process in radial basis function neural networks. The stages of high cholesterol detection process are images processing namely grayscale process, thresholding, histogram equalization, segmentation, and detection process is using radial basis function neural network. The percentage success rate of the recognition pattern of iris images for detecting high cholesterol is 89%.

Conjugation metabolism of fat-soluble vitamins by cytosolic sulfotransferases

Conjugation metabolism of fat-soluble vitamins by cytosolic sulfotransferases

Paying attention to the small things: trace minerals and vitamins impact pregnancy wastage

Pregnancy wastage resulting from abortion and stillbirth are a confounding problem for practitioners given the low rate of confirmatory diagnosis. The role of nutrition has been implicated in fetal development and postnatal survival yet minimal evidence has been provided to support a diagnostic connection. This clinical review will provide the background to understanding trace mineral and fat-soluble vitamin metabolism during gestation, implications on abortion, stillbirth, and neonatal survival, and opportunities for diagnosis and prevention. Histologic lesions in aborted or stillborn calves consistent with either iodine or selenium deficiency support a direct role of these trace minerals. Comparison of hepatic mineral concentrations in aborted, stillborn, and abattoir calves suggests other trace mineral and vitamin A deficiencies in these losses, but a more definitive cause and effect association is needed. Maternal nutrition during gestation is critical to ensuring adequate trace mineral and vitamin status during fetal development and into early postnatal life.

脂溶性ビタミンと遺伝子多型 : 代謝および臨床との関連( 第66回大会シンポジウム「栄養と臨床におけるビタミンの遺伝子多型に基づいたテーラーメイド摂取の有用性」)

脂溶性ビタミンと遺伝子多型 : 代謝および臨床との関連( 第66回大会シンポジウム「栄養と臨床におけるビタミンの遺伝子多型に基づいたテーラーメイド摂取の有用性」)

Conjugated linoleic acid influences the metabolism of tocopherol in lactating rats but has little effect on tissue tocopherol concentrations in pups.

BackgroundConjugated linoleic acid (CLA) is known to affect the lipid metabolism in growing and lactating animals. However, potential effects on the metabolism of fat-soluble vitamins in lactating animals and co-occurring effects on their offspring are unknown. We aimed to investigate the effects of dietary CLA on concentrations of tocopherol in various tissues of lactating rats and their offspring and expression of genes involved in tocopherol metabolism.MethodsTwenty-eight Wistar Han rats were allocated to 2 groups and fed either a control diet (control group) or a diet containing 0.9 % of cis-9, trans-11 and trans-10, cis-12 (1:1) CLA (CLA group) during pregnancy and lactation. Feed intake of dams and body weight of dams and their pups were recorded weekly. Tocopherol concentrations in various body tissues were determined at day 14 of lactation in dams and 1, 7 and 14 days after birth in pups. Expression of selected genes involved in metabolism of tocopherol was determined in dams and pups. The data were statistically analysed by analysis of variance.ResultsFeed intake and body weight development of nursing rats and their pups was similar in both groups. In livers of CLA-fed dams, tocopherol concentrations decreased by 24 % but expression of TTPA and CYP3A1, involved in tocopherol transport and metabolism, were not influenced. In the dams’ adipose tissue, gene expression of receptors involved in tissue tocopherol uptake, LDLR and SCARB1, but not of LPL, increased by 30 to 50 % and tocopherol concentrations increased by 47 % in CLA-fed compared to control dams. Expression of LPL, LDLR and SCARB1 in mammary gland was not influenced by CLA-feeding. Tocopherol concentrations in the pup’s livers and lungs were similar in both groups, but at 14 days of age, adipose tissue tocopherol concentrations, and LDLR and SCARB1 expression, were higher in the CLA-exposed pups.ConclusionsWe show that dietary CLA affects tissue concentrations of tocopherol in lactating rats and tocopherol metabolism in rats and pups, but hardly influences tissue tocopherol concentrations in their offspring. This indicates that supplementation of CLA in pregnant and lactating animals is uncritical considering the tocopherol status of new-borns.

Plasma turnover of 3,4-didehydroretinol (vitamin A2) increases in vitamin A-deficient rats fed low versus high dietary fat

Relationships between increased adiposity and fat-soluble vitamin storage and metabolism are poorly understood. To examine these associations, 6% or 21% dietary fat was fed to rats for 11 weeks and tissue vitamin A storage determined. Two levels of supplemental vitamin A were administered. At the end of the tenth week, 3,4-didehydroretinol (DR) was administered orally, and its kinetics were followed for 1 week in serum and tissues. Model-based compartmental analysis was applied to these data. Kidney total retinol (R) concentrations were elevated in rats fed 6% compared with 21% dietary fat (n = 24/group). The fractional transfer coefficient (FTC) describing the movement of tracer from plasma to extravascular stores was two times higher in the 6% compared with the 21% fat group. Consistent with the elevated renal R in 6% fat fed rats, there was a 2-fold increase in the FTC representing tracer distribution from plasma to kidney in the 6% compared with 21% fat group. Taken together with a fat main effect on renal vitamin A, our data support the evidence that faster turnover of kidney R may help set the mechanism governing vitamin A tissue distribution during deficiency. Rats fed 21% versus 6% dietary fat conserved hepatic R more efficiently.

Safety assessment of common foods enriched with natural nonesterified plant sterols

To assess safety during a diet based on low-fat foods enriched with nonesterified wood-derived plant sterols and mineral nutrients related to serum phytosterol, sex hormone and fat-soluble vitamin metabolism. Seventy-one study participants (52 women, 19 men) with mild-to-moderate hypercholesterolemia completed the double-blind, placebo-controlled feeding trial lasting for 15 weeks. The subjects were randomly allocated to the sterol group receiving food items enriched with mineral nutrients as well as with a total of 1.25, 2.5 and 5.0 g per day of plant sterols during the first, second and third 5-week periods, respectively, or to the placebo group receiving similar food items without plant sterols. This outpatient clinical trial with free-living subjects was carried out at two hospital clinics. Two significant findings were observed. Serum sitosterol concentrations increased from 2.84 to 5.35 mg l(-1) (P<0.004 vs placebo) but those of serum total plant sterols did not because of compensatory changes in other phytosterols. The highest plant sterol levels did not exceed 0.6% of total serum sterols. Serum alpha-tocopherol concentrations decreased in the sterol group by 10% (P<0.0002), but the between-group difference disappeared after adjusting for the change in the carrier (LDL cholesterol). Fifteen-week consumption of natural nonesterified plant sterol-enriched food does not cause any serious adverse effects during such a period. However, serum alpha-tocopherol levels were somewhat reduced in the sterol group suggesting that long-term effects of plant sterols on serum fat-soluble vitamin concentrations should be further explored, especially in relation to very low-fat diets.

A PASSION FOR P450s (REMEMBRANCES OF THE EARLY HISTORY OF RESEARCH ON CYTOCHROME P450)

Many members of the superfamily of hemeproteins, known as cytochrome P450 (P450 or CYP), are currently described in the literature (over 2000 at the date of this writing) [see Nelson, 2003 (http://drnelson.utmem.edu/CytochromeP450.html)]. In mammalian tissues, the P450s play central roles in drug and xenobiotic metabolism as well as steroid hormone synthesis, fat-soluble vitamin metabolism, and the conversion of polyunsaturated fatty acids to biologically active molecules. P450s also play a major role in plants by catalyzing the synthesis of a large number of secondary metabolites. Today we appreciate the unique oxygen chemistry catalyzed by the P450 enzymes as well as the dramatic effect of protein structural changes resulting in modifications of substrate specificity. Recent scientific advances have shown the importance of genetic differences (polymorphisms) in altering the physiological response of an animal to endo- and exo-biotic chemicals. In many instances these changes can be directly attributed to small differences in the amino acid sequence of a P450. The present article describes some of the early events associated with the establishment of the biological function of P450s. The 1950s and 1960s showed the transition of P450 from an unknown spectroscopic curiosity to the major player it now occupies in maintaining cellular homeostasis. The P450s are now recognized to occupy a great variety of phylogenetically distributed isoform activities. Much has been learned about the P450s, but much more remains as poorly understood. It has been almost 50 years since this class of unique proteins were discovered and their catalytic functions characterized. The present article describes the background and early history of research leading to our present knowledge of the cytochromes P450. Hopefully we will learn lessons from this history as we venture forward down the path of future scientific discovery.