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[PMID]: 29198193 [Au] Autor: Cai Z; Mai K; Ai Q [Ad] Endereço: Key Laboratory of Aquaculture Nutrition and Feed (Ministry of Agriculture) & Key Laboratory of Mariculture (Ministry of Education),Ocean University of China,5 Yushan Road,Qingdao,Shandong 266003,People's Republic of China. [Ti] Título: Regulation of hepatic lipid deposition by phospholipid in large yellow croaker. [So] Source: Br J Nutr;118(12):999-1009, 2017 Dec. [Is] ISSN: 1475-2662 [Cp] País de publicação: England [La] Idioma: eng [Ab] Resumo: Dietary phospholipid (PL) supplementation has been shown to reduce lipid accumulation in the tissues of farmed fish; however, the mechanisms underlying this effect are largely unknown. Thus, the present study was conducted to evaluate the potential impacts of PL on hepatic lipid metabolism both in vivo and in vitro. For in vivo study, four experimental diets - low lipid and low PL diet, as control diet (LL-LP diet, containing 12 % lipid and 1·5 % PL), low-lipid and high-PL diet (containing 12 % lipid and 8 % PL), high-lipid and low-PL diet (HL-LP diet, containing 20 % lipid and 1·5 % PL) and high-lipid and high-PL diet (HL-HP diet, containing 20 % lipid and 8 % PL) - were randomly allocated to four groups of large yellow croaker (Larimichthys crocea) (three cages per group) with similar initial body weight (approximately 8 g). For in vitro study, primary hepatocytes isolated from large yellow croaker were incubated either with graded levels of phosphatidylcholine (PC) (0-250 µm) or small interfering RNA (siRNA) for CTP: choline phosphate cytidylyltranferase α (CCTα) (siRNA-CCTα). Results showed that survival was independent of dietary treatments (P>0·05). Weight gain and feed efficiency in the HL-HP group were significantly higher than in the LL-LP and HL-LP groups (P<0·05). High level of dietary PL could markedly reduce abnormal hepatic lipid accumulation induced by the HL-LP diet (P<0·05). Similarly, compared with the corresponding controls, a significant decrease/increase in lipid content was observed in primary hepatocytes incubated with PC/siRNA-CCTα (P<0·05). High level of dietary PL reversed the HL-LP diet-induced increased levels of mRNA of fatty acid uptake and lipid synthesis related genes (P<0·05). In addition, High level of dietary PL markedly down-regulated the transcript levels of fatty acid oxidation-related genes and enhanced the transcript levels of VLDL assembly-related genes regardless of dietary lipid levels (P<0·05). Compared with corresponding controls, primary hepatocytes treated with PC showed significantly higher mRNA expression of lipid synthesis and VLDL assembly-related genes and lower mRNA expression of fatty acid oxidation-related genes, with hepatocytes treated with siRNA-CCTα exhibiting the opposite trend (P<0·05). In summary, these results demonstrated that high level of dietary PL might reverse the HL-LP diet-induced abnormal lipid accumulation in the liver through inhibiting fatty acid uptake and lipid synthesis, together with promoting the lipid export at the transcriptional level. Lipid export-promoting effect of PC was confirmed by in vitro studies. The present study showed for the first time that PL or PC could influence various metabolic pathways to regulate hepatic lipid deposition in fish at least at the transcriptional level. [Mh] Termos MeSH primário: Dieta/veterinária Metabolismo dos Lipídeos Fígado/metabolismo Perciformes/metabolismo Fosfolipídeos/administração & dosagem [Mh] Termos MeSH secundário: Ração Animal Animais Antígenos CD36/genética Antígenos CD36/metabolismo Células Cultivadas Diacilglicerol O-Aciltransferase/genética Diacilglicerol O-Aciltransferase/metabolismo Ácido Graxo Sintases/genética Ácido Graxo Sintases/metabolismo Proteínas de Transporte de Ácido Graxo/genética Proteínas de Transporte de Ácido Graxo/metabolismo Proteínas de Ligação a Ácido Graxo/genética Proteínas de Ligação a Ácido Graxo/metabolismo Ácidos Graxos/metabolismo Proteínas de Peixes/genética Proteínas de Peixes/metabolismo Hepatócitos/metabolismo Lipase/genética Lipase/metabolismo Lipase Lipoproteica/genética Lipase Lipoproteica/metabolismo Fosfatidilcolinas/administração & dosagem Proteína de Ligação a Elemento Regulador de Esterol 1/genética Proteína de Ligação a Elemento Regulador de Esterol 1/metabolismo [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (CD36 Antigens); 0 (Fatty Acid Transport Proteins); 0 (Fatty Acid-Binding Proteins); 0 (Fatty Acids); 0 (Fish Proteins); 0 (Phosphatidylcholines); 0 (Phospholipids); 0 (Sterol Regulatory Element Binding Protein 1); EC 2.3.1.20 (Diacylglycerol O-Acyltransferase); EC 2.3.1.85 (Fatty Acid Synthases); EC 3.1.1.3 (Lipase); EC 3.1.1.34 (Lipoprotein Lipase) [Em] Mês de entrada: 1712 [Cu] Atualização por classe: 171227 [Lr] Data última revisão: 171227 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 171205 [St] Status: MEDLINE [do] DOI: 10.1017/S000711451700294X

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[PMID]: 28672005 [Au] Autor: Cubizolle A; Guillou L; Mollereau B; Hamel CP; Brabet P [Ad] Endereço: Inserm U1051, Institute for Neurosciences of Montpellier, Montpellier, France. [Ti] Título: Fatty acid transport protein 1 regulates retinoid metabolism and photoreceptor development in mouse retina. [So] Source: PLoS One;12(7):e0180148, 2017. [Is] ISSN: 1932-6203 [Cp] País de publicação: United States [La] Idioma: eng [Ab] Resumo: In retinal pigment epithelium (RPE), RPE65 catalyzes the isomerization of all-trans-retinyl fatty acid esters to 11-cis-retinol in the visual cycle and controls the rhodopsin regeneration rate. However, the mechanisms by which these processes are regulated are still unclear. Fatty Acid Transport Protein 1 (FATP1) is involved in fatty acid uptake and lipid metabolism in a variety of cell types. FATP1 co-localizes with RPE65 in RPE and inhibits its isomerase activity in vitro. Here, we further investigated the role of FATP1 in the visual cycle using transgenic mice that overexpress human FATP1 specifically in the RPE (hFATP1TG mice). The mice displayed no delay in the kinetics of regeneration of the visual chromophore 11-cis-retinal after photobleaching and had no defects in light sensitivity. However, the total retinoid content was higher in the hFATP1TG mice than in wild type mice, and the transgenic mice also displayed an age-related accumulation (up to 40%) of all-trans-retinal and retinyl esters that was not observed in control mice. Consistent with these results, hFATP1TG mice were more susceptible to light-induced photoreceptor degeneration. hFATP1 overexpression also induced an ~3.5-fold increase in retinosome autofluorescence, as measured by two-photon microscopy. Interestingly, hFATP1TG retina contained ~25% more photoreceptor cells and ~35% longer outer segments than wild type mice, revealing a non-cell-autonomous effect of hFATP1 expressed in the RPE. These data are the first to show that FATP1-mediated fatty acid uptake in the RPE controls both retinoid metabolism in the outer retina and photoreceptor development. [Mh] Termos MeSH primário: Proteínas de Transporte de Ácido Graxo/fisiologia Células Fotorreceptoras de Vertebrados/metabolismo Retina/metabolismo Retinoides/metabolismo [Mh] Termos MeSH secundário: Animais Eletrorretinografia Seres Humanos Camundongos Visão Ocular [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (Fatty Acid Transport Proteins); 0 (Retinoids); 0 (Slc27a1 protein, mouse) [Em] Mês de entrada: 1710 [Cu] Atualização por classe: 171006 [Lr] Data última revisão: 171006 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170704 [St] Status: MEDLINE [do] DOI: 10.1371/journal.pone.0180148

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[PMID]: 28522731 [Au] Autor: Zabielski P; Chacinska M; Charkiewicz K; Baranowski M; Gorski J; Blachnio-Zabielska AU [Ad] Endereço: Department of Medical BiologyMedical University of Bialystok, Bialystok, Poland. [Ti] Título: Effect of metformin on bioactive lipid metabolism in insulin-resistant muscle. [So] Source: J Endocrinol;233(3):329-340, 2017 Jun. [Is] ISSN: 1479-6805 [Cp] País de publicação: England [La] Idioma: eng [Ab] Resumo: Intramuscular accumulation of bioactive lipids leads to insulin resistance and type 2 diabetes (T2D). There is lack of consensus concerning which of the lipid mediators has the greatest impact on muscle insulin action Our aim was to elucidate the effects of high-fat diet (HFD) and metformin (Met) on skeletal muscle bioactive lipid accumulation and insulin resistance (IR) in rats. We employed a [U- C]palmitate isotope tracer and mass spectrometry to measure the content and fractional synthesis rate (FSR) of intramuscular long-chain acyl-CoA (LCACoA), diacylglycerols (DAG) and ceramide (Cer). Eight weeks of HFD-induced intramuscular accumulation of LCACoA, DAG and Cer accompanied by both systemic and skeletal muscle IR. Metformin treatment improved insulin sensitivity at both systemic and muscular level by the augmentation of Akt/PKB and AS160 phosphorylation and decreased the content of DAG and Cer and their respective FSR. Principal component analysis (PCA) of lipid variables revealed that altered skeletal muscle IR was associated with lipid species containing 18-carbon acyl-chain, especially with C18:0-Cer, C18:1-Cer, 18:0/18:2-DAG and 18:2/18:2-DAG, but not palmitate-derived lipids. It is concluded that the insulin-sensitizing action of metformin in skeletal muscle is associated with decreased 18-carbon acyl-chain-derived bioactive lipids. [Mh] Termos MeSH primário: Resistência à Insulina/fisiologia Metabolismo dos Lipídeos/efeitos dos fármacos Metformina/farmacologia Músculo Esquelético/efeitos dos fármacos [Mh] Termos MeSH secundário: Animais Coenzima A Ligases/genética Coenzima A Ligases/metabolismo Dieta Hiperlipídica/efeitos adversos Proteínas de Transporte de Ácido Graxo/genética Proteínas de Transporte de Ácido Graxo/metabolismo Ácidos Graxos não Esterificados/sangue Regulação da Expressão Gênica/efeitos dos fármacos Regulação da Expressão Gênica/fisiologia Masculino Metformina/administração & dosagem Músculo Esquelético/metabolismo Ratos Ratos Wistar [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (Fatty Acid Transport Proteins); 0 (Fatty Acids, Nonesterified); 9100L32L2N (Metformin); EC 6.2.1.- (Coenzyme A Ligases) [Em] Mês de entrada: 1709 [Cu] Atualização por classe: 170911 [Lr] Data última revisão: 170911 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170520 [St] Status: MEDLINE [do] DOI: 10.1530/JOE-16-0381

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[PMID]: 28389350 [Au] Autor: Damasceno L; Ritter G; Batt CA [Ad] Endereço: Cornell University-Ludwig Institute for Cancer Research Partnership Laboratory, Ithaca, NY, United States. [Ti] Título: Process development for production and purification of the Schistosoma mansoni Sm14 antigen. [So] Source: Protein Expr Purif;134:72-81, 2017 Jun. [Is] ISSN: 1096-0279 [Cp] País de publicação: United States [La] Idioma: eng [Ab] Resumo: The trematode Schistosoma mansoni Sm14 antigen was expressed in the yeast Pichia pastoris and secreted into the culture medium at yields of approximately 250 mg L . Sm14 belongs to a family of fatty-acid binding proteins and appears to play an important role in uptake, transport, and compartmentalization of lipids in S. mansoni and it is a potential vaccine candidate in both humans and domesticated animals. The Sm14 gene was codon-optimized for expression in P. pastoris, and placed under transcription of the strong methanol inducible AOX1 promoter. Mut transformants were selected and used in fed-batch cultivation using a 2.5L fermenter equipped with an on-line methanol control system in order to maintain constant methanol levels during induction. Optimal conditions for the expression of Sm14 by P. pastoris were found to be: dissolved oxygen at 40%, temperature of 25 °C, pH 5.0, and a constant methanol concentration of 1 gL . Our results show that a correctly processed Sm14 was secreted into the culture medium at levels of approximately 250  mg L . Sm14 from clarified culture medium was purified using a two-step procedure: anion-exchange chromatography followed by hydrophobic interaction chromatography, resulting in >95% purity with a final yield of 40% from the starting cell culture medium. This product has been tested in preliminary clinical trials and shown to elicit an antibody response with no adverse reactions. [Mh] Termos MeSH primário: Antígenos de Helmintos Proteínas de Transporte de Ácido Graxo Expressão Gênica Proteínas de Helminto Pichia/metabolismo Schistosoma mansoni/genética Vacinas [Mh] Termos MeSH secundário: Animais Antígenos de Helmintos/biossíntese Antígenos de Helmintos/genética Antígenos de Helmintos/imunologia Antígenos de Helmintos/isolamento & purificação Proteínas de Transporte de Ácido Graxo/biossíntese Proteínas de Transporte de Ácido Graxo/genética Proteínas de Transporte de Ácido Graxo/imunologia Proteínas de Transporte de Ácido Graxo/isolamento & purificação Proteínas de Helminto/biossíntese Proteínas de Helminto/genética Proteínas de Helminto/imunologia Proteínas de Helminto/isolamento & purificação Seres Humanos Pichia/genética Proteínas Recombinantes/biossíntese Proteínas Recombinantes/genética Proteínas Recombinantes/imunologia Proteínas Recombinantes/isolamento & purificação Schistosoma mansoni/imunologia Vacinas/biossíntese Vacinas/genética Vacinas/imunologia Vacinas/isolamento & purificação [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (Antigens, Helminth); 0 (Fatty Acid Transport Proteins); 0 (Helminth Proteins); 0 (Recombinant Proteins); 0 (Vaccines); 138017-01-3 (SM14 protein, Schistosoma mansoni) [Em] Mês de entrada: 1708 [Cu] Atualização por classe: 170807 [Lr] Data última revisão: 170807 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170409 [St] Status: MEDLINE

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[PMID]: 28381288 [Au] Autor: Adibi JJ; Buckley JP; Lee MK; Williams PL; Just AC; Zhao Y; Bhat HK; Whyatt RM [Ad] Endereço: Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, 130 Desoto Street, Parran Hall 5132, Pittsburgh, PA, 15261, USA. adibij@pitt.edu. [Ti] Título: Maternal urinary phthalates and sex-specific placental mRNA levels in an urban birth cohort. [So] Source: Environ Health;16(1):35, 2017 Apr 05. [Is] ISSN: 1476-069X [Cp] País de publicação: England [La] Idioma: eng [Ab] Resumo: BACKGROUND: Prenatal urinary concentrations of phthalates in women participants in an urban birth cohort were associated with outcomes in their children related to neurodevelopment, autoimmune disease risk, and fat mass at 3,5,7, and 8 years of life. Placental biomarkers and outcomes at birth may offer biologic insight into these associations. This is the first study to address these associations with candidate genes from the phthalate and placenta literature, accounting for sex differences, and using absolute quantitation methods for mRNA levels. METHODS: We measured candidate mRNAs in 180 placentas sampled at birth (HSD17B1, AHR, CGA, CYP19A1, SLC27A4, PTGS2, PPARG, CYP11A1) by quantitative PCR and an absolute standard curve. We estimated associations of log mRNA with quartiles of urinary phthalate monoesters using linear mixed models. Phthalate metabolites (N = 358) and mRNAs (N = 180) were transformed to a z-score and modeled as independent, correlated vectors in relation to large for gestational age (LGA) and gestational diabetes mellitus (GDM). RESULTS: CGA was associated with 4 out of 6 urinary phthalates. CGA was 2.0 log units lower at the 3 vs. 1 quartile of mono-n-butyl phthalate (MnBP) (95% confidence interval (CI): -3.5, -0.5) in male placentas, but 0.6 log units higher (95% CI: -0.8, 1.9) in female placentas (sex interaction p = 0.01). There was an inverse association of MnBP with PPARG in male placentas (-1.1 log units at highest vs. lowest quartile, 95% CI: -2.0, -0.1). CY19A1, CYP11A1, CGA were associated with one or more of the following in a sex-specific manner: monobenzyl phthalate (MBzP), MnBP, mono-iso-butyl phthalate (MiBP). These 3 mRNAs were lower by 1.4-fold (95% CI: -2.4, -1.0) in male GDM placentas vs. female and non-GDM placentas (p-value for interaction = 0.04). The metabolites MnBP/MiBP were 16% higher (95% CI: 0, 22) in GDM pregnancies. CONCLUSIONS: Prenatal concentrations of certain phthalates and outcomes at birth were modestly associated with molecular changes in fetal placental tissue during pregnancy. Associations were stronger in male vs. female placentas, and associations with MnBP and MiBP were stronger than other metabolites. Placental mRNAs are being pursued further as potential mediators of exposure-induced risks to the health of the child. [Mh] Termos MeSH primário: Poluentes Ambientais/urina Exposição Materna Ácidos Ftálicos/urina Placenta/metabolismo RNA Mensageiro/metabolismo [Mh] Termos MeSH secundário: Adulto Aromatase/genética Enzima de Clivagem da Cadeia Lateral do Colesterol/genética Estradiol Desidrogenases/genética Proteínas de Transporte de Ácido Graxo/genética Feminino Expressão Gênica Subunidade alfa de Hormônios Glicoproteicos/genética Seres Humanos Masculino PPAR gama/genética Gravidez Receptores de Hidrocarboneto Arílico/genética Caracteres Sexuais População Urbana Adulto Jovem [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (Environmental Pollutants); 0 (Fatty Acid Transport Proteins); 0 (Glycoprotein Hormones, alpha Subunit); 0 (PPAR gamma); 0 (Phthalic Acids); 0 (RNA, Messenger); 0 (Receptors, Aryl Hydrocarbon); 0 (SLC27A4 protein, human); EC 1.1.1.62 (Estradiol Dehydrogenases); EC 1.1.1.62 (HSD17B1 protein, human); EC 1.14.14.1 (Aromatase); EC 1.14.14.1 (CYP19A1 protein, human); EC 1.14.15.6 (Cholesterol Side-Chain Cleavage Enzyme) [Em] Mês de entrada: 1710 [Cu] Atualização por classe: 171003 [Lr] Data última revisão: 171003 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170407 [St] Status: MEDLINE [do] DOI: 10.1186/s12940-017-0241-5

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[PMID]: 28369884 [Au] Autor: Murphy EJ [Ad] Endereço: Department of Biomedical Sciences, School of Medicine and Health Sciences, University of North Dakota, Grand Forks, North Dakota, USA. [Ti] Título: The blood-brain barrier and protein-mediated fatty acid uptake: role of the blood-brain barrier as a metabolic barrier: An Editorial Comment for 'The blood-brain barrier fatty acid transport protein 1 (FATP1/SLC27A1) supplies docosahexaenoic acid to the brain, and insulin facilitates transport'. [So] Source: J Neurochem;141(3):324-329, 2017 May. [Is] ISSN: 1471-4159 [Cp] País de publicação: England [La] Idioma: eng [Ab] Resumo: Read the commented article 'The blood-brain barrier fatty acid transport protein 1 (FATP1/SLC27A1) supplies docosahexaenoic acid to the brain, and insulin facilitates transport' on page 400. [Mh] Termos MeSH primário: Barreira Hematoencefálica/química Barreira Hematoencefálica/metabolismo Ácidos Docosa-Hexaenoicos/metabolismo Proteínas de Transporte de Ácido Graxo/metabolismo Ácidos Graxos/metabolismo Insulina/metabolismo [Mh] Termos MeSH secundário: Animais Transporte Biológico Seres Humanos [Pt] Tipo de publicação: EDITORIAL [Nm] Nome de substância: 0 (Fatty Acid Transport Proteins); 0 (Fatty Acids); 0 (Insulin); 0 (SLC27A1 protein, human); 0 (SLC27A4 protein, human); 25167-62-8 (Docosahexaenoic Acids) [Em] Mês de entrada: 1705 [Cu] Atualização por classe: 170502 [Lr] Data última revisão: 170502 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170404 [St] Status: MEDLINE [do] DOI: 10.1111/jnc.14000

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[PMID]: 28346411 [Au] Autor: Lynes MD; Leiria LO; Lundh M; Bartelt A; Shamsi F; Huang TL; Takahashi H; Hirshman MF; Schlein C; Lee A; Baer LA; May FJ; Gao F; Narain NR; Chen EY; Kiebish MA; Cypess AM; Blüher M; Goodyear LJ; Hotamisligil GS; Stanford KI; Tseng YH [Ad] Endereço: Section on Integrative Physiology and Metabolism, Joslin Diabetes Center, Harvard Medical School, Boston, Massachusetts, USA. [Ti] Título: The cold-induced lipokine 12,13-diHOME promotes fatty acid transport into brown adipose tissue. [So] Source: Nat Med;23(5):631-637, 2017 May. [Is] ISSN: 1546-170X [Cp] País de publicação: United States [La] Idioma: eng [Ab] Resumo: Brown adipose tissue (BAT) and beige adipose tissue combust fuels for heat production in adult humans, and so constitute an appealing target for the treatment of metabolic disorders such as obesity, diabetes and hyperlipidemia. Cold exposure can enhance energy expenditure by activating BAT, and it has been shown to improve nutrient metabolism. These therapies, however, are time consuming and uncomfortable, demonstrating the need for pharmacological interventions. Recently, lipids have been identified that are released from tissues and act locally or systemically to promote insulin sensitivity and glucose tolerance; as a class, these lipids are referred to as 'lipokines'. Because BAT is a specialized metabolic tissue that takes up and burns lipids and is linked to systemic metabolic homeostasis, we hypothesized that there might be thermogenic lipokines that activate BAT in response to cold. Here we show that the lipid 12,13-dihydroxy-9Z-octadecenoic acid (12,13-diHOME) is a stimulator of BAT activity, and that its levels are negatively correlated with body-mass index and insulin sensitivity. Using a global lipidomic analysis, we found that 12,13-diHOME was increased in the circulation of humans and mice exposed to cold. Furthermore, we found that the enzymes that produce 12,13-diHOME were uniquely induced in BAT by cold stimulation. The injection of 12,13-diHOME acutely activated BAT fuel uptake and enhanced cold tolerance, which resulted in decreased levels of serum triglycerides. Mechanistically, 12,13-diHOME increased fatty acid (FA) uptake into brown adipocytes by promoting the translocation of the FA transporters FATP1 and CD36 to the cell membrane. These data suggest that 12,13-diHOME, or a functional analog, could be developed as a treatment for metabolic disorders. [Mh] Termos MeSH primário: Tecido Adiposo Marrom/metabolismo Temperatura Baixa Ácidos Graxos/metabolismo Resistência à Insulina Obesidade/metabolismo Ácidos Oleicos/metabolismo Termogênese [Mh] Termos MeSH secundário: Tecido Adiposo Marrom/efeitos dos fármacos Animais Transporte Biológico/efeitos dos fármacos Antígenos CD36/efeitos dos fármacos Antígenos CD36/metabolismo Membrana Celular/efeitos dos fármacos Membrana Celular/metabolismo Metabolismo Energético/efeitos dos fármacos Proteínas de Transporte de Ácido Graxo/efeitos dos fármacos Proteínas de Transporte de Ácido Graxo/metabolismo Feminino Fluordesoxiglucose F18 Seres Humanos Masculino Camundongos Ácidos Oleicos/biossíntese Ácidos Oleicos/farmacologia Sobrepeso/metabolismo Tomografia Computadorizada com Tomografia por Emissão de Pósitrons RNA Mensageiro/metabolismo Compostos Radiofarmacêuticos Triglicerídeos/metabolismo [Pt] Tipo de publicação: JOURNAL ARTICLE; VIDEO-AUDIO MEDIA [Nm] Nome de substância: 0 (12,13-dihydroxyoctadecenoic acid); 0 (CD36 Antigens); 0 (Fatty Acid Transport Proteins); 0 (Fatty Acids); 0 (Oleic Acids); 0 (RNA, Messenger); 0 (Radiopharmaceuticals); 0 (Slc27a1 protein, mouse); 0 (Triglycerides); 0Z5B2CJX4D (Fluorodeoxyglucose F18) [Em] Mês de entrada: 1708 [Cu] Atualização por classe: 171126 [Lr] Data última revisão: 171126 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170328 [St] Status: MEDLINE [do] DOI: 10.1038/nm.4297

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[PMID]: 28245829 [Au] Autor: Tan Z; Black W; Yoon JM; Shanks JV; Jarboe LR [Ad] Endereço: 4134 Biorenewables Research Laboratory, Department of Chemical and Biological Engineering, Iowa State University, Ames, IA, 50011, USA. [Ti] Título: Improving Escherichia coli membrane integrity and fatty acid production by expression tuning of FadL and OmpF. [So] Source: Microb Cell Fact;16(1):38, 2017 Feb 28. [Is] ISSN: 1475-2859 [Cp] País de publicação: England [La] Idioma: eng [Ab] Resumo: BACKGROUND: Construction of microbial biocatalysts for the production of biorenewables at economically viable yields and titers is frequently hampered by product toxicity. Membrane damage is often deemed as the principal mechanism of this toxicity, particularly in regards to decreased membrane integrity. Previous studies have attempted to engineer the membrane with the goal of increasing membrane integrity. However, most of these works focused on engineering of phospholipids and efforts to identify membrane proteins that can be targeted to improve fatty acid production have been unsuccessful. RESULTS: Here we show that deletion of outer membrane protein ompF significantly increased membrane integrity, fatty acid tolerance and fatty acid production, possibly due to prevention of re-entry of short chain fatty acids. In contrast, deletion of fadL resulted in significantly decreased membrane integrity and fatty acid production. Consistently, increased expression of fadL remarkably increased membrane integrity and fatty acid tolerance while also increasing the final fatty acid titer. This 34% increase in the final fatty acid titer was possibly due to increased membrane lipid biosynthesis. Tuning of fadL expression showed that there is a positive relationship between fadL abundance and fatty acid production. Combinatorial deletion of ompF and increased expression of fadL were found to have an additive role in increasing membrane integrity, and was associated with a 53% increase the fatty acid titer, to 2.3 g/L. CONCLUSIONS: These results emphasize the importance of membrane proteins for maintaining membrane integrity and production of biorenewables, such as fatty acids, which expands the targets for membrane engineering. [Mh] Termos MeSH primário: Proteínas da Membrana Bacteriana Externa/genética Membrana Celular/fisiologia Proteínas de Escherichia coli/genética Escherichia coli/genética Escherichia coli/fisiologia Proteínas de Transporte de Ácido Graxo/genética Ácidos Graxos/biossíntese Porinas/genética [Mh] Termos MeSH secundário: Proteínas da Membrana Bacteriana Externa/metabolismo Proteínas de Escherichia coli/metabolismo Proteínas de Transporte de Ácido Graxo/metabolismo Deleção de Genes Expressão Gênica Lipídeos de Membrana/biossíntese Deleção de Sequência [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (Bacterial Outer Membrane Proteins); 0 (Escherichia coli Proteins); 0 (Fatty Acid Transport Proteins); 0 (Fatty Acids); 0 (Membrane Lipids); 0 (OmpF protein); 0 (Porins); 0 (fadL protein, E coli) [Em] Mês de entrada: 1704 [Cu] Atualização por classe: 170420 [Lr] Data última revisão: 170420 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170302 [St] Status: MEDLINE [do] DOI: 10.1186/s12934-017-0650-8

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[PMID]: 28190774 [Au] Autor: Falkevall A; Mehlem A; Palombo I; Heller Sahlgren B; Ebarasi L; He L; Ytterberg AJ; Olauson H; Axelsson J; Sundelin B; Patrakka J; Scotney P; Nash A; Eriksson U [Ad] Endereço: Division of Vascular Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, 171 77 Stockholm, Sweden. [Ti] Título: Reducing VEGF-B Signaling Ameliorates Renal Lipotoxicity and Protects against Diabetic Kidney Disease. [So] Source: Cell Metab;25(3):713-726, 2017 Mar 07. [Is] ISSN: 1932-7420 [Cp] País de publicação: United States [La] Idioma: eng [Ab] Resumo: Diabetic kidney disease (DKD) is the most common cause of severe renal disease, and few treatment options are available today that prevent the progressive loss of renal function. DKD is characterized by altered glomerular filtration and proteinuria. A common observation in DKD is the presence of renal steatosis, but the mechanism(s) underlying this observation and to what extent they contribute to disease progression are unknown. Vascular endothelial growth factor B (VEGF-B) controls muscle lipid accumulation through regulation of endothelial fatty acid transport. Here, we demonstrate in experimental mouse models of DKD that renal VEGF-B expression correlates with the severity of disease. Inhibiting VEGF-B signaling in DKD mouse models reduces renal lipotoxicity, re-sensitizes podocytes to insulin signaling, inhibits the development of DKD-associated pathologies, and prevents renal dysfunction. Further, we show that elevated VEGF-B levels are found in patients with DKD, suggesting that VEGF-B antagonism represents a novel approach to treat DKD. [Mh] Termos MeSH primário: Nefropatias Diabéticas/metabolismo Nefropatias Diabéticas/prevenção & controle Rim/patologia Lipídeos/toxicidade Transdução de Sinais Fator B de Crescimento do Endotélio Vascular/metabolismo [Mh] Termos MeSH secundário: Adulto Idoso Albuminúria/complicações Albuminúria/metabolismo Albuminúria/patologia Animais Anticorpos Neutralizantes/administração & dosagem Anticorpos Neutralizantes/farmacologia Diabetes Mellitus Experimental/complicações Diabetes Mellitus Experimental/metabolismo Diabetes Mellitus Experimental/patologia Diabetes Mellitus Tipo 1/complicações Diabetes Mellitus Tipo 1/metabolismo Diabetes Mellitus Tipo 1/patologia Diabetes Mellitus Tipo 2/complicações Diabetes Mellitus Tipo 2/metabolismo Diabetes Mellitus Tipo 2/patologia Nefropatias Diabéticas/patologia Modelos Animais de Doenças Progressão da Doença Dislipidemias/complicações Dislipidemias/metabolismo Dislipidemias/patologia Proteínas de Transporte de Ácido Graxo/metabolismo Feminino Deleção de Genes Seres Humanos Insulina/farmacologia Rim/efeitos dos fármacos Rim/metabolismo Rim/fisiopatologia Masculino Camundongos Endogâmicos C57BL Meia-Idade Podócitos/efeitos dos fármacos Podócitos/metabolismo Podócitos/patologia Transdução de Sinais/efeitos dos fármacos Regulação para Cima/efeitos dos fármacos Adulto Jovem [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (Antibodies, Neutralizing); 0 (Fatty Acid Transport Proteins); 0 (Insulin); 0 (Lipids); 0 (Slc27a4 protein, mouse); 0 (Vascular Endothelial Growth Factor B) [Em] Mês de entrada: 1707 [Cu] Atualização por classe: 170713 [Lr] Data última revisão: 170713 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170214 [St] Status: MEDLINE

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MEDLINE

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[PMID]: 28178239 [Au] Autor: Arif A; Terenzi F; Potdar AA; Jia J; Sacks J; China A; Halawani D; Vasu K; Li X; Brown JM; Chen J; Kozma SC; Thomas G; Fox PL [Ad] Endereço: Department of Cellular and Molecular Medicine, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio 44195, USA. [Ti] Título: EPRS is a critical mTORC1-S6K1 effector that influences adiposity in mice. [So] Source: Nature;542(7641):357-361, 2017 02 16. [Is] ISSN: 1476-4687 [Cp] País de publicação: England [La] Idioma: eng [Ab] Resumo: Metabolic pathways that contribute to adiposity and ageing are activated by the mammalian target of rapamycin complex 1 (mTORC1) and p70 ribosomal protein S6 kinase 1 (S6K1) axis. However, known mTORC1-S6K1 targets do not account for observed loss-of-function phenotypes, suggesting that there are additional downstream effectors of this pathway. Here we identify glutamyl-prolyl-tRNA synthetase (EPRS) as an mTORC1-S6K1 target that contributes to adiposity and ageing. Phosphorylation of EPRS at Ser999 by mTORC1-S6K1 induces its release from the aminoacyl tRNA multisynthetase complex, which is required for execution of noncanonical functions of EPRS beyond protein synthesis. To investigate the physiological function of EPRS phosphorylation, we generated Eprs knock-in mice bearing phospho-deficient Ser999-to-Ala (S999A) and phospho-mimetic (S999D) mutations. Homozygous S999A mice exhibited low body weight, reduced adipose tissue mass, and increased lifespan, similar to S6K1-deficient mice and mice with adipocyte-specific deficiency of raptor, an mTORC1 constituent. Substitution of the Eprs allele in S6K1-deficient mice normalized body mass and adiposity, indicating that EPRS phosphorylation mediates S6K1-dependent metabolic responses. In adipocytes, insulin stimulated S6K1-dependent EPRS phosphorylation and release from the multisynthetase complex. Interaction screening revealed that phospho-EPRS binds SLC27A1 (that is, fatty acid transport protein 1, FATP1), inducing its translocation to the plasma membrane and long-chain fatty acid uptake. Thus, EPRS and FATP1 are terminal mTORC1-S6K1 axis effectors that are critical for metabolic phenotypes. [Mh] Termos MeSH primário: Adiposidade Aminoacil-tRNA Sintetases/metabolismo Complexos Multiproteicos/metabolismo Proteínas Quinases S6 Ribossômicas 90-kDa/metabolismo Serina-Treonina Quinases TOR/metabolismo [Mh] Termos MeSH secundário: Proteínas Adaptadoras de Transdução de Sinal/deficiência Adipócitos/metabolismo Envelhecimento/metabolismo Aminoacil-tRNA Sintetases/química Aminoacil-tRNA Sintetases/genética Animais Peso Corporal Membrana Celular/metabolismo Proteínas de Transporte de Ácido Graxo/metabolismo Ácidos Graxos/química Ácidos Graxos/metabolismo Feminino Insulina/metabolismo Longevidade/genética Masculino Alvo Mecanístico do Complexo 1 de Rapamicina Camundongos Mutação Tamanho do Órgão Fosforilação Fosfosserina/metabolismo Ligação Proteica Transporte Proteico Proteína Associada Regulatória a mTOR Proteínas Quinases S6 Ribossômicas 90-kDa/deficiência [Pt] Tipo de publicação: JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T [Nm] Nome de substância: 0 (Adaptor Proteins, Signal Transducing); 0 (Fatty Acid Transport Proteins); 0 (Fatty Acids); 0 (Insulin); 0 (Multiprotein Complexes); 0 (Regulatory-Associated Protein of mTOR); 0 (Rptor protein, mouse); 0 (Slc27a1 protein, mouse); 17885-08-4 (Phosphoserine); EC 2.7.1.1 (TOR Serine-Threonine Kinases); EC 2.7.11.1 (Mechanistic Target of Rapamycin Complex 1); EC 2.7.11.1 (Ribosomal Protein S6 Kinases, 90-kDa); EC 2.7.11.1 (Rps6ka1 protein, mouse); EC 6.1.1.- (Amino Acyl-tRNA Synthetases); EC 6.1.1.- (glutamyl-prolyl-tRNA synthetase) [Em] Mês de entrada: 1706 [Cu] Atualização por classe: 171116 [Lr] Data última revisão: 171116 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170209 [St] Status: MEDLINE [do] DOI: 10.1038/nature21380

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