PubMed

Related Articles Panomics for Precision Medicine. Trends Mol Med. 2017 Dec 04;: Authors: Sandhu C, Qureshi A, Emili A Abstract Medicine is poised to undergo a digital transformation. High-throughput platforms are creating terabytes of genomic, transcriptomic, proteomic, and metabolomic data. The challenge is to interpret these data in a meaningful manner - to uncover relationships that are not readily apparent between molecular profiles and states of health or disease. This will require the development of novel data pipelines and computational tools. The combined analysis of multi-dimensional data is referred to as 'panomics'. The ultimate hope of integrative panomics is that it will lead to the discovery and application of novel markers and targeted therapeutics that drive forward a new era of 'precision medicine' where inter-individual variation is accounted for in the treatment of patients. PMID: 29217119 [PubMed - as supplied by publisher]

16 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2017/12/08PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

16 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2017/12/08PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

22 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2017/12/07PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

22 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2017/12/07PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

Related Articles Phytochemical variation among the traditional Chinese medicine Mu Dan Pi from Paeonia suffruticosa (tree peony). Phytochemistry. 2017 Dec 02;146:16-24 Authors: Li SS, Wu Q, Yin DD, Feng CY, Liu ZA, Wang LS Abstract Mu Dan Pi is a traditional Chinese medicine used to treat inflammation, cancer, allergies, diabetes, angiocardiopathy, and neurodegenerative diseases. In this study, the metabolome variation within Mu Dan Pi collected from 372 tree peony cultivars was systematically investigated. In total, 42 metabolites were identified, comprising of 14 monoterpene glucosides, 11 tannins, 8 paeonols, 6 flavonoids, and 3 phenols. All cultivars revealed similar metabolite profiles, however, they were further classified into seven groups on the basis of their varying metabolite contents by hierarchical cluster analysis. Traditional cultivars for Mu Dan Pi were found to have very low metabolite contents, falling into clusters I and II. Cultivars with the highest amounts of metabolites were grouped in clusters VI and VII. Five potential cultivars, namely, 'Bai Yuan Qi Guan', 'Cao Zhou Hong', 'Da Zong Zi', 'Sheng Dan Lu', and 'Cheng Xin', with high contents of monoterpene glycosides, tannins, and paeonols, were further screened. Interestingly, the majority of investigated cultivars had relatively higher metabolite contents compared to the traditional medicinal tree peony cultivars. PMID: 29207319 [PubMed - as supplied by publisher]

Related Articles 8-oxoguanine DNA glycosylase (Ogg1) controls hepatic gluconeogenesis. DNA Repair (Amst). 2017 Nov 28;61:56-62 Authors: Scheffler K, Rachek L, You P, Rowe AD, Wang W, Kuśnierczyk A, Kittelsen L, Bjørås M, Eide L Abstract Mitochondrial DNA (mtDNA) resides in close proximity to metabolic reactions, and is maintained by the 8-oxoguanine DNA glycosylase (Ogg1) and other members of the base excision repair pathway. Here, we tested the hypothesis that changes in liver metabolism as under fasting/feeding conditions would be sensed by liver mtDNA, and that Ogg1 deficient mice might unravel a metabolic phenotype. Wild type (WT) and ogg1-/- mice were either fed ad libitum or subjected to fasting for 24h, and the corresponding effects on liver gene expression, DNA damage, as well as serum values were analyzed. Ogg1 deficient mice fed ad libitum exhibited hyperglycemia, elevated insulin levels and higher liver glycogen content as well as increased accumulation of 8oxoG in mtDNA compared to age- and gender matched WT mice. Interestingly, these phenotypes were absent in ogg1-/- mice during fasting. Gene expression and functional analyses suggest that the diabetogenic phenotype in the ogg1-/- mice is due to a failure to suppress gluconeogensis in the fed state. The ogg1-/- mice exhibited reduced mitochondrial electron transport chain (ETC) capacity and a combined low activity of the pyruvate dehydrogenase (PDH), alluding to inefficient channeling of glycolytic products into the citric acid cycle. Our data demonstrate a physiological role of base excision repair that goes beyond DNA maintenance, and implies that DNA repair is involved in regulating metabolism. PMID: 29207315 [PubMed - as supplied by publisher]

Related Articles High-resolution metabolomics determines the mode of onset of type 2 diabetes in a 3-year prospective cohort study. Int J Mol Med. 2017 Nov 21;: Authors: Lee Y, Pamungkas AD, Medriano CAD, Park J, Hong S, Jee SH, Park YH Abstract Type 2 diabetes mellitus (DM) is a progressive disease and the rate of progression from non-diabetes to DM varies considerably between individuals, ranging from a few months to many years. It is important to understand the mechanisms underlying the progression of diabetes. In the present study, a high-resolution metabolomics (HRM) analysis was performed to detect potential biomarkers and pathways regulating the mode of onset by comparing subjects who developed and did not develop type 2 DM at the second year in a 3-year prospective cohort study. Metabolic profiles correlated with progression to DM were examined. The subjects (n=98) were classified into four groups: Control (did not develop DM for 3 years), DM (diagnosed with DM at the start of the study), DM onset at the third year and DM onset at the second year. The focus was on the comparison of serum samples of the DM groups with onset at the second and third year from the first year, where these two groups had not developed DM, yet. Analyses involved sample examination using liquid chromatography-mass spectrometry-based HRM and multivariate statistical analysis of the data. Metabolic differences were identified across all analyses with the affected pathways involved in metabolism associated with steroid biosynthesis and bile acid biosynthesis. In the first year, higher levels of cholesterol {mass-to charge ratio (m/z) 369.35, (M+H-H2O)+}, 25-hydroxycholesterol [m/z 403.36, (M+H)+], 3α,7α-dihydroxy-5β-cholestane [m/z 443.33, (M+K)+], 4α-methylzymosterol-4-carboxylate [m/z 425.34, (M+H‑H2O)+], and lower levels of 24,25-dihydrolanosterol [m/z 429.40, (M+H)+] were evident in the group with DM onset at the second year compared with those in the group with DM onset at the third year. These results, with a focus on the cholesterol biosynthesis pathway, point to important aspects in the development of DM and may aid in the development of more effective means of treatment and prevention. PMID: 29207196 [PubMed - as supplied by publisher]

Related Articles Impact of intratumoral heterogeneity of breast cancer tissue on quantitative metabolomics using high-resolution magic angle spinning 1 H NMR spectroscopy. NMR Biomed. 2017 Dec 05;: Authors: Gogiashvili M, Horsch S, Marchan R, Gianmoena K, Cadenas C, Tanner B, Naumann S, Ersova D, Lippek F, Rahnenführer J, Andersson JT, Hergenröder R, Lambert J, Hengstler JG, Edlund K Abstract High-resolution magic angle spinning (HR MAS) nuclear magnetic resonance (NMR) spectroscopy is increasingly being used to study metabolite levels in human breast cancer tissue, assessing, for instance, correlations with prognostic factors, survival outcome or therapeutic response. However, the impact of intratumoral heterogeneity on metabolite levels in breast tumor tissue has not been studied comprehensively. More specifically, when biopsy material is analyzed, it remains questionable whether one biopsy is representative of the entire tumor. Therefore, multi-core sampling (n = 6) of tumor tissue from three patients with breast cancer, followed by lipid (0.9- and 1.3-ppm signals) and metabolite quantification using HR MAS 1 H NMR, was performed, resulting in the quantification of 32 metabolites. The mean relative standard deviation across all metabolites for the six tumor cores sampled from each of the three tumors ranged from 0.48 to 0.74. This was considerably higher when compared with a morphologically more homogeneous tissue type, here represented by murine liver (0.16-0.20). Despite the seemingly high variability observed within the tumor tissue, a random forest classifier trained on the original sample set (training set) was, with one exception, able to correctly predict the tumor identity of an independent series of cores (test set) that were additionally sampled from the same three tumors and analyzed blindly. Moreover, significant differences between the tumors were identified using one-way analysis of variance (ANOVA), indicating that the intertumoral differences for many metabolites were larger than the intratumoral differences for these three tumors. That intertumoral differences, on average, were larger than intratumoral differences was further supported by the analysis of duplicate tissue cores from 15 additional breast tumors. In summary, despite the observed intratumoral variability, the results of the present study suggest that the analysis of one, or a few, replicates per tumor may be acceptable, and supports the feasibility of performing reliable analyses of patient tissue. PMID: 29206323 [PubMed - as supplied by publisher]

Related Articles Merging FT-IR and NGS for simultaneous phenotypic and genotypic identification of pathogenic Candida species. PLoS One. 2017;12(12):e0188104 Authors: Colabella C, Corte L, Roscini L, Shapaval V, Kohler A, Tafintseva V, Tascini C, Cardinali G Abstract The rapid and accurate identification of pathogen yeast species is crucial for clinical diagnosis due to the high level of mortality and morbidity induced, even after antifungal therapy. For this purpose, new rapid, high-throughput and reliable identification methods are required. In this work we described a combined approach based on two high-throughput techniques in order to improve the identification of pathogenic yeast strains. Next Generation Sequencing (NGS) of ITS and D1/D2 LSU marker regions together with FTIR spectroscopy were applied to identify 256 strains belonging to Candida genus isolated in nosocomial environments. Multivariate data analysis (MVA) was carried out on NGS and FT-IR data-sets, separately. Strains of Candida albicans, C. parapsilosis, C. glabrata and C. tropicalis, were identified with high-throughput NGS sequencing of ITS and LSU markers and then with FTIR. Inter- and intra-species variability was investigated by consensus principal component analysis (CPCA) which combines high-dimensional data of the two complementary analytical approaches in concatenated PCA blocks normalized to the same weight. The total percentage of correct identification reached around 97.4% for C. albicans and 74% for C. parapsilosis while the other two species showed lower identification rates. Results suggested that the identification success increases with the increasing number of strains actually used in the PLS analysis. The absence of reliable FT-IR libraries in the current scenario is the major limitation in FTIR-based identification of strains, although this metabolomics fingerprint represents a valid and affordable aid to rapid and high-throughput to clinical diagnosis. According to our data, FT-IR libraries should include some tens of certified strains per species, possibly over 50, deriving from diverse sources and collected over an extensive time period. This implies a multidisciplinary effort of specialists working in strain isolation and maintenance, molecular taxonomy, FT-IR technique and chemo-metrics, data management and data basing. PMID: 29206226 [PubMed - in process]

Related Articles Macroamidine Formation in Bottromycins Is Catalyzed by a Divergent YcaO Enzyme. J Am Chem Soc. 2017 Dec 05;: Authors: Franz L, Adam S, Santos-Aberturas J, Truman AW, Koehnke J Abstract The YcaO superfamily of proteins catalyzes the phosphorylation of peptide backbone amide bonds, which leads to the formation of azolines and azoles in ribosomally synthesized and post-translationally modified peptides (RiPPs). Bottromycins are RiPPs with potent antimicrobial activity, and their biosynthetic pathway contains two divergent, stand-alone YcaO enzymes, IpoC and PurCD. From an untargeted metabolomics approach, it had been suggested that PurCD acts with a partner protein to form the 12-membered macroamidine unique to bottromycins. Here we report the biochemical characterization of IpoC and PurCD. We demonstrate that IpoC installs a cysteine-derived thiazoline, whereas PurCD alone is sufficient to create the macroamidine structure. Both enzymes are catalytically promiscuous, and we generated 10 different macroamidines. Our data provide important insights into the versatility of YcaO enzymes, their ability to utilize different nucleophiles and provide a framework for the creation of novel bottromycin derivatives with enhanced bioactivity. PMID: 29206037 [PubMed - as supplied by publisher]

Related Articles [Research Progress on Estimation of Early Postmortem Interval]. Fa Yi Xue Za Zhi. 2016 Dec;32(6):444-447 Authors: Tao L, Ma JL, Chen L Abstract Estimation of postmortem interval （PMI） is very important for judging the nature of cases, restricting the scope of investigation and suspect, which is always the emphasis and difficulty for forensic pathology. Early postmortem interval is the time between 0 and 24 hours after death. Due to the shorter time after the case occurred, precisely estimating early postmortem interval can help solve crimes, which has important significance in forensic medicine. In recent years, series of advanced methods and technologies are used to estimate the early PMI by the internal and overseas scholars who work in the forensic area. This paper reviews the research progress on fluids biochemistry, supravital reactions, metabolomics, imageology and the degradation rule of genetic material to provide a new idea to the study and application for estimation of early PMI. PMID: 29205974 [PubMed - in process]

Related Articles Colon Ascendens Stent Peritonitis (CASP) Induces Excessive Inflammation and Systemic Metabolic Dysfunction in a Septic Rat Model. J Proteome Res. 2017 Dec 05;: Authors: Zhang L, Tian Y, Yang J, Li J, Tang H, Wang Y Abstract The colon ascendens stent peritonitis (CASP) surgery creates a leakage of intestinal contents, resulting in polymicrobial sepsis associated with a high risk for postoperative multiple organ failure and death in surgical patients. To evaluate the effects of CASP on multiple organs, we analyzed the systemic metabolic consequences in liver, kidney, lung and heart of rats after CASP by employing a combination of metabolomics, clinical chemistry and biological assays. We found that CASP surgery after 18 h caused significant elevations of lipid, amino acids, acetate, choline, PC and GPC in rat liver together with significant depletion of glucose and glycogen. Marked elevations of organic acids including lactate, acetate and creatine and amino acids accompanied with decline for glucose, betaine, TMAO, nucleotides and a range of organic osmolytes, such as myo-inositol, choline, PC and GPC are observed in the kidney of 18 h-postoperative rat. Furthermore, 18 h-postoperative rats exhibited accumulations of lipid, amino acids and depletions of taurine, myo-inositol, choline, PC and GPC, and some nucleotides including uridine, inosine and adenosine in the lung. In addition, significant elevations of some amino acids, uracil, betaine, choline metabolites, together with depletion of inosine-5'-monophosphate were only observed in the heart of 18 h-postoperative rats. These findings provide new insights into pathological consequences of CASP surgery, which are important for timely prognosis of sepsis. PMID: 29205045 [PubMed - as supplied by publisher]

Related Articles Rhizobium Impacts on Seed Productivity, Quality, and Protection of Pisum sativum upon Disease Stress Caused by Didymella pinodes: Phenotypic, Proteomic, and Metabolomic Traits. Front Plant Sci. 2017;8:1961 Authors: Ranjbar Sistani N, Kaul HP, Desalegn G, Wienkoop S Abstract In field peas, ascochyta blight is one of the most common fungal diseases caused by Didymella pinodes. Despite the high diversity of pea cultivars, only little resistance has been developed until to date, still leading to significant losses in grain yield. Rhizobia as plant growth promoting endosymbionts are the main partners for establishment of symbiosis with pea plants. The key role of Rhizobium as an effective nitrogen source for legumes seed quality and quantity improvement is in line with sustainable agriculture and food security programs. Besides these growth promoting effects, Rhizobium symbiosis has been shown to have a priming impact on the plants immune system that enhances resistance against environmental perturbations. This is the first integrative study that investigates the effect of Rhizobium leguminosarum bv. viceae (Rlv) on phenotypic seed quality, quantity and fungal disease in pot grown pea (Pisum sativum) cultivars with two different resistance levels against D. pinodes through metabolomics and proteomics analyses. In addition, the pathogen effects on seed quantity components and quality are assessed at morphological and molecular level. Rhizobium inoculation decreased disease severity by significant reduction of seed infection level. Rhizobium symbiont enhanced yield through increased seed fresh and dry weights based on better seed filling. Rhizobium inoculation also induced changes in seed proteome and metabolome involved in enhanced P. sativum resistance level against D. pinodes. Besides increased redox and cell wall adjustments light is shed on the role of late embryogenesis abundant proteins and metabolites such as the seed triterpenoid Soyasapogenol. The results of this study open new insights into the significance of symbiotic Rhizobium interactions for crop yield, health and seed quality enhancement and reveal new metabolite candidates involved in pathogen resistance. PMID: 29204150 [PubMed]

Related Articles Genomics of Metal Stress-Mediated Signalling and Plant Adaptive Responses in Reference to Phytohormones. Curr Genomics. 2017 Dec;18(6):512-522 Authors: Shukla A, Srivastava S, Suprasanna P Abstract Introduction: As a consequence of a sessile lifestyle, plants often have to face a number of life threatening abiotic and biotic stresses. Plants counteract the stresses through morphological and physiological adaptations, which are imparted through flexible and well-coordinated network of signalling and effector molecules, where phytohormones play important role. Hormone synthesis, signal transduction, perception and cross-talks create a complex network. Omics approaches, which include transcriptomics, genomics, proteomics and metabolomics, have opened new paths to understand such complex networks. Objective: This review concentrates on the importance of phytohormones and enzymatic expressions under metal stressed conditions. Conclusion: This review sheds light on gene expressions involved in plant adaptive and defence responses during metal stress. It gives an insight of genomic approaches leading to identification and functional annotation of genes involved in phytohormone signal transduction and perception. Moreover, it also emphasizes on perception, signalling and cross-talks among various phytohormones and other signalling components viz., Reactive Oxygen Species (ROS) and Reactive Nitrogen Species (RNS). PMID: 29204080 [PubMed]

Related Articles Adipose tissue mitochondrial capacity associates with long-term weight loss success. Int J Obes (Lond). 2017 Dec 05;: Authors: Jokinen R, Rinnankoski-Tuikka R, Kaye S, Saarinen L, Heinonen S, Myöhänen M, Rappou E, Jukarainen S, Rissanen A, Pessia A, Velagapudi V, Virtanen KA, Pirinen E, Pietiläinen KH Abstract OBJECTIVES: We investigated whether (1) subcutaneous adipose tissue (SAT) mitochondrial capacity predicts weight loss success and (2) weight loss ameliorates obesity-related SAT mitochondrial abnormalities. METHODS: SAT biopsies were obtained from 19 clinically healthy obese subjects (BMI 34.6±2.7 kg/m2) during a weight-loss intervention (0, 5, and 12 months) and from 19 lean reference subjects (BMI 22.7±1.1 kg/m2) at baseline. Based on one-year weight loss outcome, the subjects were divided into two groups: continuous weight losers (WL, n=6) and weight regainers (WR, n=13). Main outcome measures included SAT mitochondrial pathways from transcriptomics, mitochondrial amount (mitochondrial DNA (mtDNA), Porin protein levels), mtDNA-encoded transcripts, oxidative phosphorylation (OXPHOS) proteins, and plasma metabolites of the mitochondrial branched-chain amino acid catabolism (BCAA) pathway. SAT and visceral adipose tissue (VAT) glucose uptake was measured with positron emission tomography. RESULTS: Despite similar baseline clinical characteristics, SAT in the WL group exhibited higher gene expression level of nuclear-encoded mitochondrial pathways (P=0.0224 OXPHOS, P=0.0086 tricarboxylic acid cycle, P=0.0074 fatty acid beta-oxidation and P=0.0122 BCAA), mtDNA transcript COX1 (P=0.0229) and protein level of Porin (P=0.0462) than the WR group. Many baseline mitochondrial parameters correlated with weight loss success, and with SAT and VAT glucose uptake. During weight loss, the nuclear-encoded mitochondrial pathways were downregulated, together with increased plasma metabolite levels of BCAAs in both groups. MtDNA copy number increased in the WR group at 5 months (P=0.012), but decreased to baseline level between 5 to 12 months (P=0.015). The only significant change in the WL group for mtDNA was a reduction between 5 and 12 months (P=0.004). The levels of Porin did not change in either group upon weight loss. CONCLUSIONS: Higher mitochondrial capacity in SAT predicts good long-term weight loss success. Weight loss does not ameliorate SAT mitochondrial downregulation and based on pathway expression, may paradoxically further reduce it. DATA AVAILABILITY: The transcriptomics data generated in this study have been deposited to the Gene Expression Omnibus public repository, accession number GSE103769.International Journal of Obesity accepted article preview online, 05 December 2017. doi:10.1038/ijo.2017.299. PMID: 29203860 [PubMed - as supplied by publisher]

Related Articles Pitfalls in the detection of citrullination and carbamylation. Autoimmun Rev. 2017 Dec 01;: Authors: Verheul MK, van Veelen PA, van Delft MAM, de Ru A, Janssen GMC, Rispens T, Toes REM, Trouw LA Abstract Carbamylation and citrullination are both post-translational modifications against which (auto)antibodies can be detected in sera of rheumatoid arthritis (RA) patients. Carbamylation is the chemical modification of a lysine into a homocitrulline, whereas citrullination is an enzymatic conversion of an arginine into a citrulline. It is difficult to distinguish between the two resulting amino acids due to similarities in structure. However, differentiation between citrulline and homocitrulline is important to understand the antigens that induce antibody production and to determine which modified antigens are present in target tissues. We have observed in literature that conclusions are frequently drawn regarding the citrullination or carbamylation of proteins based on reagents that are not able to distinguish between these two modifications. Therefore, we have analyzed a wide spectrum of methods and describe here which method we consider most optimal to distinguish between citrulline and homocitrulline. We have produced several carbamylated and citrullinated proteins and investigated the specificity of (commercial) antibodies by both ELISA and western blot. Furthermore, detection methods based on chemical modifications, such as the anti-modified citrulline-"Senshu" method and also mass spectrometry were investigated for their capacity to distinguish between carbamylation and citrullination. We observed that some antibodies are able to distinguish between carbamylation and citrullination, but an overlap in reactivity is often present in the commercially available anti-citrulline antibodies. Finally, we conclude that the use of mass spectrometry is currently essential to differentiate between citrullinated and carbamylated proteins present in complex biological samples. PMID: 29203292 [PubMed - as supplied by publisher]

Related Articles Transcriptomic and metabolic responses of Calotropis procera to salt and drought stress. BMC Plant Biol. 2017 Dec 04;17(1):231 Authors: Mutwakil MZ, Hajrah NH, Atef A, Edris S, Sabir MJ, Al-Ghamdi AK, Sabir MJSM, Nelson C, Makki RM, Ali HM, El-Domyati FM, Al-Hajar ASM, Gloaguen Y, Al-Zahrani HS, Sabir JSM, Jansen RK, Bahieldin A, Hall N Abstract BACKGROUND: Calotropis procera is a wild plant species in the family Apocynaceae that is able to grow in harsh, arid and heat stressed conditions. Understanding how this highly adapted plant persists in harsh environments should inform future efforts to improve the hardiness of crop and forage plant species. To study the plant response to droμght and osmotic stress, we treated plants with polyethylene glycol and NaCl and carried out transcriptomic and metabolomics measurements across a time-course of five days. RESULTS: We identified a highly dynamic transcriptional response across the time-course including dramatic changes in inositol signaling, stress response genes and cytokinins. The resulting metabolome changes also involved sharp increases of myo-inositol, a key signaling molecule and elevated amino acid metabolites at later times. CONCLUSIONS: The data generated here provide a first glimpse at the expressed genome of C. procera, a plant that is exceptionally well adapted to arid environments. We demonstrate, through transcriptome and metabolome analysis that myo-inositol signaling is strongly induced in response to drought and salt stress and that there is elevation of amino acid concentrations after prolonged osmotic stress. This work should lay the foundations of future studies in adaptation to arid environments. PMID: 29202709 [PubMed - in process]

Related Articles Intestinal epithelial cell caveolin 1 regulates fatty acid and lipoprotein cholesterol plasma levels. Dis Model Mech. 2017 Mar 01;10(3):283-295 Authors: Otis JP, Shen MC, Quinlivan V, Anderson JL, Farber SA Abstract Caveolae and their structural protein caveolin 1 (CAV1) have roles in cellular lipid processing and systemic lipid metabolism. Global deletion of CAV1 in mice results in insulin resistance and increases in atherogenic plasma lipids and cholesterol, but protects from diet-induced obesity and atherosclerosis. Despite the fundamental role of the intestinal epithelia in the regulation of dietary lipid processing and metabolism, the contributions of CAV1 to lipid metabolism in this tissue have never been directly investigated. In this study the cellular dynamics of intestinal Cav1 were visualized in zebrafish and the metabolic contributions of CAV1 were determined with mice lacking CAV1 in intestinal epithelial cells (CAV1IEC-KO). Live imaging of Cav1-GFP and fluorescently labeled caveolae cargos shows localization to the basolateral and lateral enterocyte plasma membrane (PM), suggesting Cav1 mediates transport between enterocytes and the submucosa. CAV1IEC-KO mice are protected from the elevation in circulating fasted low-density lipoprotein (LDL) cholesterol associated with a high-fat diet (HFD), but have increased postprandial LDL cholesterol, total free fatty acids (FFAs), palmitoleic acid, and palmitic acid. The increase in circulating FAs in HFD CAV1IEC-KO mice is mirrored by decreased hepatic FAs, suggesting a non-cell-autonomous role for intestinal epithelial cell CAV1 in promoting hepatic FA storage. In conclusion, CAV1 regulates circulating LDL cholesterol and several FA species via the basolateral PM of enterocytes. These results point to intestinal epithelial cell CAV1 as a potential therapeutic target to lower circulating FFAs and LDL cholesterol, as high levels are associated with development of type II diabetes and cardiovascular disease. PMID: 28130355 [PubMed - indexed for MEDLINE]

24 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2017/12/05PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.