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2.
Int J Mol Sci ; 22(10)2021 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-34069420

RESUMO

Selenium-binding protein 1 (Selenbp1) is a 2,3,7,8-tetrechlorodibenzo-p-dioxin inducible protein whose function is yet to be comprehensively elucidated. As the highly homologous isoform, Selenbp2, is expressed at low levels in the kidney, it is worthwhile comparing wild-type C57BL mice and Selenbp1-deficient mice under dioxin-free conditions. Accordingly, we conducted a mouse metabolomics analysis under non-dioxin-treated conditions. DNA microarray analysis was performed based on observed changes in lipid metabolism-related factors. The results showed fluctuations in the expression of numerous genes. Real-time RT-PCR confirmed the decreased expression levels of the cytochrome P450 4a (Cyp4a) subfamily, known to be involved in fatty acid ω- and ω-1 hydroxylation. Furthermore, peroxisome proliferator-activated receptor-α (Pparα) and retinoid-X-receptor-α (Rxrα), which form a heterodimer with Pparα to promote gene expression, were simultaneously reduced. This indicated that reduced Cyp4a expression was mediated via decreased Pparα and Rxrα. In line with this finding, increased levels of leukotrienes and prostaglandins were detected. Conversely, decreased hydrogen peroxide levels and reduced superoxide dismutase (SOD) activity supported the suppression of the renal expression of Sod1 and Sod2 in Selenbp1-deficient mice. Therefore, we infer that ablation of Selenbp1 elicits oxidative stress caused by increased levels of superoxide anions, which alters lipid metabolism via the Pparα pathway.


Assuntos
Metabolismo dos Lipídeos/genética , Proteínas de Ligação a Selênio/metabolismo , Animais , Citocromo P-450 CYP4A/metabolismo , Expressão Gênica , Rim/patologia , Lipídeos/genética , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Estresse Oxidativo/genética , PPAR alfa/metabolismo , PPAR alfa/fisiologia , RNA Mensageiro/genética , Receptor X Retinoide alfa/metabolismo , Receptor X Retinoide alfa/fisiologia , Proteínas de Ligação a Selênio/genética , Fatores de Transcrição/metabolismo
3.
Int J Mol Sci ; 22(11)2021 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-34067363

RESUMO

Grapevine downy mildew, caused by the biotrophic oomycete Plasmopara viticola, is one of the most severe and devastating diseases in viticulture. Unravelling the grapevine defence mechanisms is crucial to develop sustainable disease control measures. Here we provide new insights concerning fatty acid's (FA) desaturation, a fundamental process in lipid remodelling and signalling. Previously, we have provided evidence that lipid signalling is essential in the establishment of the incompatible interaction between grapevine and Plasmopara viticola. In the first hours after pathogen challenge, jasmonic acid (JA) accumulation, activation of its biosynthetic pathway and an accumulation of its precursor, the polyunsaturated α-linolenic acid (C18:3), were observed in the leaves of the tolerant genotype, Regent. This work was aimed at a better comprehension of the desaturation processes occurring after inoculation. We characterised, for the first time in Vitis vinifera, the gene family of the FA desaturases and evaluated their involvement in Regent response to Plasmopara viticola. Upon pathogen challenge, an up-regulation of the expression of plastidial FA desaturases genes was observed, resulting in a higher content of polyunsaturated fatty acids (PUFAs) of chloroplast lipids. This study highlights FA desaturases as key players in membrane remodelling and signalling in grapevine defence towards biotrophic pathogens.


Assuntos
Resistência à Doença/genética , Ácidos Graxos Dessaturases/genética , Doenças das Plantas/genética , Doenças das Plantas/microbiologia , Vitis/genética , Vitis/microbiologia , Vias Biossintéticas/genética , Cloroplastos/genética , Ciclopentanos/metabolismo , Regulação da Expressão Gênica de Plantas/genética , Genótipo , Lipídeos/genética , Oomicetos/patogenicidade , Oxilipinas/metabolismo , Peronospora/patogenicidade , Folhas de Planta/genética , Folhas de Planta/microbiologia
4.
Molecules ; 26(9)2021 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-33925418

RESUMO

Fatty acid amides are a diverse family of underappreciated, biologically occurring lipids. Herein, the methods for the chemical synthesis and subsequent characterization of specific members of the fatty acid amide family are described. The synthetically prepared fatty acid amides and those obtained commercially are used as standards for the characterization and quantification of the fatty acid amides produced by biological systems, a fatty acid amidome. The fatty acid amidomes from mouse N18TG2 cells, sheep choroid plexus cells, Drosophila melanogaster, Bombyx mori, Apis mellifera, and Tribolium castaneum are presented.


Assuntos
Amidas/química , Ácidos Graxos/química , Lipídeos/química , Amidas/síntese química , Amidas/metabolismo , Animais , Abelhas/química , Bombyx/química , Linhagem Celular , Drosophila melanogaster/química , Ácidos Graxos/síntese química , Ácidos Graxos/metabolismo , Lipídeos/genética , Camundongos , Ovinos , Tribolium/química
5.
Int J Mol Sci ; 22(6)2021 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-33809364

RESUMO

The conserved VPS13 proteins constitute a new family of lipid transporters at membrane contact sites. These large proteins are suspected to bridge membranes and form a direct channel for lipid transport between organelles. Mutations in the 4 human homologs (VPS13A-D) are associated with a number of neurological disorders, but little is known about their precise functions or the relevant contact sites affected in disease. In contrast, yeast has a single Vps13 protein which is recruited to multiple organelles and contact sites. The yeast model system has proved useful for studying the function of Vps13 at different organelles and identifying the localization determinants responsible for its membrane targeting. In this review we describe recent advances in our understanding of VPS13 proteins with a focus on yeast research.


Assuntos
Transporte Biológico/genética , Membrana Celular/genética , Lipídeos/genética , Proteínas de Saccharomyces cerevisiae/genética , Membrana Celular/metabolismo , Humanos , Membranas Mitocondriais/metabolismo , Mutação/genética , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo
6.
Theranostics ; 11(9): 4061-4077, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33754048

RESUMO

Background: Diet manipulation is the basis for prevention of obesity and diabetes. The molecular mechanisms that mediate the diet-based prevention of insulin resistance are not well understood. Here, as proof-of-concept, ginger-derived nanoparticles (GDNP) were used for studying molecular mechanisms underlying GDNP mediated prevention of high-fat diet induced insulin resistance. Methods: Ginger-derived nanoparticles (GDNP) were isolated from ginger roots and administered orally to C57BL/6 high-fat diet mice. Fecal exosomes released from intestinal epithelial cells (IECs) of PBS or GDNP treated high-fat diet (HFD) fed mice were isolated by differential centrifugation. A micro-RNA (miRNA) polymerase chain reaction (PCR) array was used to profile the exosomal miRs and miRs of interest were further analyzed by quantitative real time (RT) PCR. miR-375 or antisense-miR375 was packed into nanoparticles made from the lipids extracted from GDNP. Nanoparticles was fluorescent labeled for monitoring their in vivo trafficking route after oral administration. The effect of these nanoparticles on glucose and insulin response of mice was determined by glucose and insulin tolerance tests. Results: We report that HFD feeding increased the expression of AhR and inhibited the expression of miR-375 and VAMP7. Treatment with orally administered ginger-derived nanoparticles (GDNP) resulted in reversing HFD mediated inhibition of the expression of miR-375 and VAMP7. miR-375 knockout mice exhibited impaired glucose homeostasis and insulin resistance. Induction of intracellular miR-375 led to inhibition of the expression of AhR and VAMP7 mediated exporting of miR-375 into intestinal epithelial exosomes where they were taken up by gut bacteria and inhibited the production of the AhR ligand indole. Intestinal exosomes can also traffic to the liver and be taken up by hepatocytes, leading to miR-375 mediated inhibition of hepatic AhR over-expression and inducing the expression of genes associated with the hepatic insulin response. Altogether, GDNP prevents high-fat diet-induced insulin resistance by miR-375 mediated inhibition of the aryl hydrocarbon receptor mediated pathways over activated by HFD feeding. Conclusion: Collectively our findings reveal that oral administration of GDNP to HFD mice improves host glucose tolerance and insulin response via regulating AhR expression by GDNP induced miR-375 and VAMP7.


Assuntos
Bactérias/genética , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Dieta Hiperlipídica/efeitos adversos , Resistência à Insulina/genética , Insulina/genética , MicroRNAs/genética , Receptores de Hidrocarboneto Arílico/genética , Triptofanase/genética , Adulto , Animais , Células Cultivadas , Gengibre/química , Hepatócitos/efeitos dos fármacos , Humanos , Lipídeos/genética , Fígado/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Pessoa de Meia-Idade , Nanopartículas/administração & dosagem , Obesidade/genética , Proteínas R-SNARE/genética
7.
Nat Plants ; 7(3): 353-364, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33686223

RESUMO

Plant roots acquire nutrients and water while managing interactions with the soil microbiota. The root endodermis provides an extracellular diffusion barrier through a network of lignified cell walls called Casparian strips, supported by subsequent formation of suberin lamellae. Whereas lignification is thought to be irreversible, suberin lamellae display plasticity, which is crucial for root adaptative responses. Although suberin is a major plant polymer, fundamental aspects of its biosynthesis and turnover have remained obscure. Plants shape their root system via lateral root formation, an auxin-induced process requiring local breaking and re-sealing of endodermal lignin and suberin barriers. Here, we show that differentiated endodermal cells have a specific, auxin-mediated transcriptional response dominated by cell wall remodelling genes. We identified two sets of auxin-regulated GDSL lipases. One is required for suberin synthesis, while the other can drive suberin degradation. These enzymes have key roles in suberization, driving root suberin plasticity.


Assuntos
Proteínas de Arabidopsis/metabolismo , Arabidopsis/metabolismo , Hidrolases de Éster Carboxílico/metabolismo , Lipídeos , Domínios Proteicos , Arabidopsis/enzimologia , Proteínas de Arabidopsis/genética , Hidrolases de Éster Carboxílico/genética , Conjuntos de Dados como Assunto , Endoderma/metabolismo , Técnicas de Inativação de Genes , Ácidos Indolacéticos/metabolismo , Lipídeos/genética , Células Vegetais/metabolismo , Raízes de Plantas/metabolismo , Polimerização , Proteólise
8.
Genet Sel Evol ; 53(1): 12, 2021 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-33546581

RESUMO

BACKGROUND: Product quality and production efficiency of Atlantic salmon are, to a large extent, influenced by the deposition and depletion of lipid reserves. Fillet lipid content is a heritable trait and is unfavourably correlated with growth, thus genetic management of fillet lipid content is needed for sustained genetic progress in these two traits. The laboratory-based reference method for recording fillet lipid content is highly accurate and precise but, at the same time, expensive, time-consuming, and destructive. Here, we test the use of rapid and cheaper vibrational spectroscopy methods, namely near-infrared (NIR) and Raman spectroscopy both as individual phenotypes and phenotypic predictors of lipid content in Atlantic salmon. RESULTS: Remarkably, 827 of the 1500 individual Raman variables (i.e. Raman shifts) of the Raman spectrum were significantly heritable (heritability (h2) ranging from 0.15 to 0.65). Similarly, 407 of the 2696 NIR spectral landscape variables (i.e. wavelengths) were significantly heritable (h2 = 0.27-0.40). Both Raman and NIR spectral landscapes had significantly heritable regions, which are also informative in spectroscopic predictions of lipid content. Partial least square predicted lipid content using Raman and NIR spectra were highly concordant and highly genetically correlated with the lipid content values ([Formula: see text] = 0.91-0.98) obtained with the reference method using Lin's concordance correlation coefficient (CCC = 0.63-0.90), and were significantly heritable ([Formula: see text] = 0.52-0.67). CONCLUSIONS: Both NIR and Raman spectral landscapes show substantial additive genetic variation and are highly genetically correlated with the reference method. These findings lay down the foundation for rapid spectroscopic measurement of lipid content in salmonid breeding programmes.


Assuntos
Produtos Pesqueiros/normas , Lipídeos/análise , Característica Quantitativa Herdável , Salmo salar/genética , Análise Espectral Raman/métodos , Animais , Cruzamento/métodos , Cruzamento/normas , Metabolismo dos Lipídeos , Lipídeos/genética , Polimorfismo Genético , Padrões de Referência , Espectroscopia de Luz Próxima ao Infravermelho/métodos , Espectroscopia de Luz Próxima ao Infravermelho/normas , Análise Espectral Raman/normas
9.
Proc Natl Acad Sci U S A ; 118(6)2021 02 09.
Artigo em Inglês | MEDLINE | ID: mdl-33526687

RESUMO

Vertical sleeve gastrectomy (VSG) is one of the most effective and durable therapies for morbid obesity and its related complications. Although bile acids (BAs) have been implicated as downstream mediators of VSG, the specific mechanisms through which BA changes contribute to the metabolic effects of VSG remain poorly understood. Here, we confirm that high fat diet-fed global farnesoid X receptor (Fxr) knockout mice are resistant to the beneficial metabolic effects of VSG. However, the beneficial effects of VSG were retained in high fat diet-fed intestine- or liver-specific Fxr knockouts, and VSG did not result in Fxr activation in the liver or intestine of control mice. Instead, VSG decreased expression of positive hepatic Fxr target genes, including the bile salt export pump (Bsep) that delivers BAs to the biliary pathway. This reduced small intestine BA levels in mice, leading to lower intestinal fat absorption. These findings were verified in sterol 27-hydroxylase (Cyp27a1) knockout mice, which exhibited low intestinal BAs and fat absorption and did not show metabolic improvements following VSG. In addition, restoring small intestinal BA levels by dietary supplementation with taurocholic acid (TCA) partially blocked the beneficial effects of VSG. Altogether, these findings suggest that reductions in intestinal BAs and lipid absorption contribute to the metabolic benefits of VSG.


Assuntos
Colestanotriol 26-Mono-Oxigenase/genética , Gastrectomia/métodos , Obesidade Mórbida/cirurgia , Receptores Citoplasmáticos e Nucleares/genética , Animais , Ácidos e Sais Biliares/biossíntese , Ácidos e Sais Biliares/metabolismo , Dieta Hiperlipídica/efeitos adversos , Humanos , Metabolismo dos Lipídeos/genética , Lipídeos/genética , Camundongos , Camundongos Knockout , Obesidade Mórbida/metabolismo , Obesidade Mórbida/fisiopatologia , Perda de Peso/genética
10.
PLoS One ; 16(2): e0246417, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33571255

RESUMO

In high-density aquaculture, fish health can suffer because of excessive feeding, which causes fatty liver disease. Siberian ginseng (Acanthopanax senticosus) has been used as a feed additive to promote animal growth, immunity, and lipid metabolism. In this study, we explored the effects of A. senticosus on the physiology of hybrid yellow catfish (Tachysurus fulvidraco ♀ × Pseudobagrus vachellii ♂). A control group and five groups fed diets containing A. senticosus (0.5, 1, 2, 4, and 8 g A. senticosus/kg feed) were established and maintained for 8 weeks. Dietary supplementation with A. senticosus at 4 g/kg promoted growth of the hybrid yellow catfish. Serum total cholesterol (TC) and triacylglycerol (TG) levels at 2 g/kg A. senticosus (TC: 1.31 mmol/L; TG: 1.08 mmol/L) were significantly lower than in the control group (TC: 1.51 mmol/L; TG: 1.41 mmol/L), and 4 g/kg A. senticosus (17.20 µmol/g tissue) reduced the liver TG level compared with the control group (21.36 µmol/g tissue) (P <0.05). Comparative transcriptomic analysis of liver tissue between the control group and the group showing optimum growth (4 g/kg A. senticosus) revealed 820 differentially expressed genes and 44 significantly enriched pathways, especially lipid metabolism pathways such as unsaturated fatty acid and fatty acid metabolism. The transcript levels of five lipid metabolism-related genes were determined by quantitative real-time PCR. The results showed that 2-4 g/kg A. senticosus supplementation reduced the FADS2, ELOVL2, CYP24a, and PLPP3 transcript levels and 4 g/kg A. senticosus increased the DIO2 transcript level (P <0.05), leading to altered synthesis of TG and thyroxine and reduced fat deposition in the liver. Our results show that dietary A. senticosus affects the regulation of fat metabolism and promotes the growth of hybrid yellow catfish. A. senticosus is a healthy feed additive, and the appropriate dietary supplementation rate is 2-4 g/kg.


Assuntos
Ração Animal , Peixes-Gato/crescimento & desenvolvimento , Peixes-Gato/genética , Metabolismo dos Lipídeos , Lipídeos/genética , Ração Animal/análise , Animais , Aquicultura , Peixes-Gato/fisiologia , Suplementos Nutricionais/análise , Panax/química , Transcriptoma
11.
Arch Microbiol ; 203(3): 901-911, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33078270

RESUMO

The most important tools in killing and overcoming on the microbes and pathogens that cause diseases in medicine and/or in agriculture are the antibiotics. The discovery and synthesis of the microbial natural products or antibiotics has greatly developed genetically and biotechnologically quickly in the last decades. It is necessary to access this great genetic diversity by finding ways to increase the level of expression of these biosynthetic pathways. In this study, we carried out an improvement in the antibiotic production of weak Streptomyces graminofaciens strain NBR9 that has high lipid content; using Ultra-Violet irradiation mutagenesis. This strain was isolated from the Northern Region in the kingdom of Saudi Arabia and identified biochemically and confirmed genetically by sequencing of the 16S rRNA gene as Streptomyces graminofaciens NBR9; Accession No. (MN640578). The resultant mutant strain showed increasing in their antimicrobial activities. The methods and techniques used for the antibiotic extraction, purification, characterization and identification proved that the obtained antibiotic is same with antibiotic Carbomycin.


Assuntos
Vias Biossintéticas/genética , Microbiologia Industrial , Leucomicinas/biossíntese , Lipídeos/genética , Mutação/genética , Streptomyces/genética , Antibacterianos/biossíntese , Antibacterianos/isolamento & purificação , Antibacterianos/farmacologia , Bactérias/efeitos dos fármacos , Leucomicinas/isolamento & purificação , Leucomicinas/farmacologia , Mutagênese , RNA Ribossômico 16S/genética
12.
Biochim Biophys Acta Gen Subj ; 1865(1): 129751, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32991969

RESUMO

BACKGROUND: Congenital disorders of glycosylation (CDG) are inherited metabolic diseases caused by defects in the genes important for the process of protein and lipid glycosylation. With the ever growing number of the known subtypes and discoveries regarding the disease mechanisms and therapy development, it remains a very active field of study. SCOPE OF REVIEW: This review brings an update on the CDG-related research since 2017, describing the novel gene defects, pathobiomechanisms, biomarkers and the patients' phenotypes. We also summarize the clinical guidelines for the most prevalent disorders and the current therapeutical options for the treatable CDG. MAJOR CONCLUSIONS: In the majority of the 23 new CDG, neurological involvement is associated with other organ disease. Increasingly, different aspects of cellular metabolism (e.g., autophagy) are found to be perturbed in multiple CDG. GENERAL SIGNIFICANCE: This work highlights the recent trends in the CDG field and comprehensively overviews the up-to-date clinical recommendations.


Assuntos
Defeitos Congênitos da Glicosilação/metabolismo , Defeitos Congênitos da Glicosilação/patologia , Animais , Defeitos Congênitos da Glicosilação/genética , Defeitos Congênitos da Glicosilação/terapia , Glicosilação , Humanos , Metabolismo dos Lipídeos , Lipídeos/genética , Redes e Vias Metabólicas , Mutação , Proteínas/genética , Proteínas/metabolismo
13.
ACS Appl Mater Interfaces ; 12(50): 55649-55658, 2020 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-33270413

RESUMO

Due to the pressing need to generate specific drugs or vaccines for COVID-19 and management of its outbreak, detailed knowledge regarding the SARS-CoV-2 entry into host cells and timely, cheap, and easy-to-use detection methods are of critical importance for containing the SARS-CoV-2 epidemic. Through electrophysiology and fluorescence spectroscopy experiments, we show that even in the absence of the angiotensin-converting enzyme 2 receptor, the S1 subunit from SARS-CoV-2 spike protein binding to neutral phospholipid membranes leads to their mechanical destabilization and permeabilization. A similar cytotoxic effect of the protein was seen in human lung epithelial cells. A monoclonal antibody generated toward the S1 subunit alleviates to a considerable extent the destabilizing potential of the protein in such model membranes. Finally, we demonstrate the proof-of-concept capability of an α-hemolysin (α-HL) protein nanopore to detect in aqueous buffer and real time the region-binding domain of the S1 subunit from SARS-CoV-2 spike protein by monitoring its immunological interaction with a target antibody. Our results may offer new perspectives in understanding the pathogenesis of the SARS-CoV-2 infection, its treatment, and real-time detection.


Assuntos
COVID-19/genética , Lipídeos/genética , SARS-CoV-2/genética , Glicoproteína da Espícula de Coronavírus/genética , Anticorpos Monoclonais/genética , Anticorpos Monoclonais/imunologia , COVID-19/virologia , Vacinas contra COVID-19/genética , Vacinas contra COVID-19/imunologia , Humanos , SARS-CoV-2/patogenicidade , Glicoproteína da Espícula de Coronavírus/química , Glicoproteína da Espícula de Coronavírus/metabolismo
14.
Int J Mol Sci ; 21(23)2020 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-33255174

RESUMO

Cyanobacteria play an important role in several ecological environments, and they are widely accepted to be the ancestors of chloroplasts in modern plants and green algae. Cyanobacteria have become attractive models for metabolic engineering, with the goal of exploring them as microbial cell factories. However, the study of cyanobacterial lipids' composition and variation, and the assessment of the lipids' functional and structural roles have been largely overlooked. Here, we aimed at expanding the cyanobacterial lipidomic analytical pipeline by using an untargeted lipidomics approach. Thus, the lipid composition variation of the model cyanobacterium Synechocystis sp. PCC 6803 was investigated in response to both alternative cultivation setups and gene deletion. This approach allowed for detecting differences in total lipid content, alterations in fatty-acid unsaturation level, and adjustments of specific lipid species among the identified lipid classes. The employed method also revealed that the cultivation setup tested in this work induced a deeper alteration of the cyanobacterial cell lipidome than the deletion of a gene that results in a dramatic increase in the release of lipid-rich outer membrane vesicles. This study further highlights how growth conditions must be carefully selected when cyanobacteria are to be engineered and/or scaled-up for lipid or fatty acids production.


Assuntos
Ácidos Graxos/genética , Lipidômica , Lipídeos/genética , Lipídeos de Membrana/genética , Cianobactérias/genética , Cianobactérias/metabolismo , Deleção de Genes , Regulação Bacteriana da Expressão Gênica/genética , Engenharia Metabólica , Fotossíntese/genética
15.
J Genet Genomics ; 47(9): 523-534, 2020 09 20.
Artigo em Inglês | MEDLINE | ID: mdl-33309167

RESUMO

Apolipoprotein M (apoM) participates in both high-density lipoprotein and cholesterol metabolism. Little is known about how apoM affects lipid composition of the liver and serum. In this study, we systemically investigated the effects of apoM on liver and plasma lipidomes and how apoM participates in lipid cycling, via apoM knockout in mice and the human SMMC-7721 cell line. We used integrated mass spectrometry-based lipidomics approaches to semiquantify more than 600 lipid species from various lipid classes, which include free fatty acids, glycerolipids, phospholipids, sphingolipids, glycosphingolipids, cholesterol, and cholesteryl esters (CEs), in apoM-/- mouse. Hepatic accumulation of neutral lipids, including CEs, triacylglycerols, and diacylglycerols, was observed in apoM-/- mice; while serum lipidomic analyses showed that, in contrast to the liver, the overall levels of CEs and saturated/monounsaturated fatty acids were markedly diminished. Furthermore, the level of ApoB-100 was dramatically increased in the liver, whereas significant reductions in both ApoB-100 and low-density lipoprotein (LDL) cholesterol were observed in the serum of apoM-/- mice, which indicated attenuated hepatic LDL secretion into the circulation. Lipid profiles and proinflammatory cytokine levels indicated that apoM-/- leads to hepatic steatosis and an overall state of metabolic distress. Taken together, these results revealed that apoM knockout leads to hepatic steatosis, impaired lipid secretion, and an overall state of metabolic distress.


Assuntos
Apolipoproteínas M/genética , Lipidômica , Lipídeos/sangue , Fígado/metabolismo , Animais , Linhagem Celular , Humanos , Metabolismo dos Lipídeos/genética , Lipídeos/biossíntese , Lipídeos/genética , Lipoproteínas HDL/sangue , Lipoproteínas HDL/genética , Lipoproteínas LDL/sangue , Lipoproteínas LDL/genética , Camundongos , Camundongos Knockout , Triglicerídeos/sangue
16.
PLoS One ; 15(12): e0243919, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33326441

RESUMO

Common variants in the hepatic lipase (LIPC) gene have been shown to be associated with plasma lipid levels; however, the distribution and functional features of rare and regulatory LIPC variants contributing to the extreme lipid phenotypes are not well known. This study was aimed to catalogue LIPC variants by resequencing the entire LIPC gene in 95 non-Hispanic Whites (NHWs) and 95 African blacks (ABs) with extreme HDL-C levels followed by in silico functional analyses. A total of 412 variants, including 43 novel variants were identified; 56 were unique to NHWs and 234 were unique to ABs. Seventy-eight variants in NHWs and 89 variants in ABs were present either in high HDL-C group or low HDL-C group. Two non-synonymous variants (p.S289F, p.T405M), found in NHWs with high HDL-C group were predicted to have damaging effect on LIPC protein by SIFT, MT2 and PP2. We also found several non-coding variants that possibly reside in the circRNA and lncRNA binding sites and may have regulatory potential, as identified in rSNPbase and RegulomeDB databases. Our results shed light on the regulatory nature of rare and non-coding LIPC variants as well as suggest their important contributions in affecting the extreme HDL-C phenotypes.


Assuntos
HDL-Colesterol/sangue , LDL-Colesterol/sangue , Lipase/genética , Afro-Americanos , Alelos , Sítios de Ligação/genética , Colesterol/sangue , Colesterol/genética , Proteínas de Transferência de Ésteres de Colesterol/sangue , Proteínas de Transferência de Ésteres de Colesterol/genética , HDL-Colesterol/genética , LDL-Colesterol/genética , Grupo com Ancestrais do Continente Europeu , Feminino , Genótipo , Humanos , Íntrons/genética , Lipase/ultraestrutura , Metabolismo dos Lipídeos/genética , Lipídeos/sangue , Lipídeos/genética , Masculino , Polimorfismo de Nucleotídeo Único , Ligação Proteica/genética , Conformação Proteica , RNA Circular/sangue , RNA Circular/genética , RNA Longo não Codificante/genética , Triglicerídeos/sangue , Triglicerídeos/genética
17.
Development ; 147(24)2020 12 21.
Artigo em Inglês | MEDLINE | ID: mdl-33355243

RESUMO

Lipids exert diverse functions in living organisms. They form cellular membranes, store and transport energy and play signalling roles. Some lipid species function in all of these processes, making them ideal candidates to coordinate metabolism with cellular homeostasis and animal development. This theme was central to Suzanne Eaton's research in the fruit fly, Drosophila Here, we discuss her work on membrane lipid homeostasis in changing environments and on functions for lipids in the Hedgehog signalling pathway. We further highlight lipoproteins as inter-organ carriers of lipids and lipid-linked morphogens, which communicate dietary and developmental signals throughout the organism.


Assuntos
Proteínas Hedgehog/genética , Metabolismo dos Lipídeos/genética , Lipídeos/genética , Lipoproteínas/genética , Animais , Drosophila melanogaster/genética , Drosophila melanogaster/crescimento & desenvolvimento , Drosophila melanogaster/metabolismo , Proteínas Hedgehog/metabolismo , Homeostase/genética , Lipoproteínas/metabolismo , Transdução de Sinais/genética
18.
Sci Rep ; 10(1): 22322, 2020 12 18.
Artigo em Inglês | MEDLINE | ID: mdl-33339843

RESUMO

Late developmental stages of the marine copepods in the genus Calanus can spend extended periods in a dormant stage (diapause) that is preceded by the accumulation of large lipid stores. We assessed how lipid metabolism during development from the C4 stage to adult is altered in response to predation risk and varying food availability, to ultimately understand more of the metabolic processes during development in Calanus copepods. We used RNA sequencing to assess if perceived predation risk in combination with varied food availability affects expression of genes associated with lipid metabolism and diapause preparation in C. finmarchicus. The lipid metabolism response to predation risk differed depending on food availability, time and life stage. Predation risk caused upregulation of lipid catabolism with high food, and downregulation with low food. Under low food conditions, predation risk disrupted lipid accumulation. The copepods showed no clear signs of diapause preparation, supporting earlier observations of the importance of multiple environmental cues in inducing diapause in C. finmarchicus. This study demonstrates that lipid metabolism is a sensitive endpoint for the interacting environmental effects of predation pressure and food availability. As diapause may be controlled by lipid accumulation, our findings may contribute towards understanding processes that can ultimately influence diapause timing.


Assuntos
Copépodes/genética , Diapausa/genética , Metabolismo dos Lipídeos/genética , Lipídeos/genética , Animais , Copépodes/fisiologia , Diapausa/fisiologia , Metabolismo/genética , Comportamento Predatório/fisiologia , Estações do Ano , Análise de Sequência de RNA
19.
Sci Rep ; 10(1): 20549, 2020 11 25.
Artigo em Inglês | MEDLINE | ID: mdl-33239653

RESUMO

Dyslipidemia is a documented risk factor for cardiovascular diseases and other metabolic disorders. Therefore, the analysis of hyperlipidemia (HL)-related miRNAs is a potential approach for achieving new prognostic markers in lipid-metabolism related diseases. We aimed to analyze specific distribution of miRNAs in different tissues from HL animals. Golden Syrian hamsters were fed either regular chow (NL) or high-fat diet (HL) for 12 weeks. Microarray miRNAs profiling was performed in liver, heart and small intestine and data analyzed by R-studio software. Functional enrichment bioinformatics analysis was performed using miRWalk and DAVID tools. We observed a dysregulation of miRNAs in HL tissues evidencing a discrete distribution in the heart-liver axis and three lipid metabolism-related miRNAs were identified: hsa-miR-223-3p, hsa-miR-21-5p, and hsa-miR-146a-5p. Expression levels of these miRNAs were increased in HL livers and hearts. Functional bioinformatics analysis showed involvement of these miRNAs in the regulation of biological processes altered in HL conditions such as lipid metabolic process, fat cell differentiation, regulation of smooth muscle cells and cardiac septum development. We identified a set of miRNAs dysregulated in different tissues of HFD-induced HL hamsters. These findings motivate further studies aiming to investigate novel molecular mechanisms of lipid metabolism and atherogenic HL.


Assuntos
Dieta Hiperlipídica/efeitos adversos , Hiperlipidemias/genética , MicroRNAs/genética , Transcriptoma/genética , Animais , Biologia Computacional/métodos , Cricetinae , Expressão Gênica/genética , Perfilação da Expressão Gênica/métodos , Regulação da Expressão Gênica/genética , Hiperlipidemias/metabolismo , Metabolismo dos Lipídeos/fisiologia , Lipídeos/genética , Fígado/metabolismo
20.
Sci Rep ; 10(1): 20567, 2020 11 25.
Artigo em Inglês | MEDLINE | ID: mdl-33239708

RESUMO

The role of metabolic syndrome (MetS) as a preceding metabolic state for type 2 diabetes and cardiovascular disease is widely recognised. To accumulate knowledge of the pathological mechanisms behind the condition at the methylation level, we conducted an epigenome-wide association study (EWAS) of MetS and its components, testing 1187 individuals of European ancestry for approximately 470 000 methylation sites throughout the genome. Methylation site cg19693031 in gene TXNIP -previously associated with type 2 diabetes, glucose and lipid metabolism, associated with fasting glucose level (P = 1.80 × 10-8). Cg06500161 in gene ABCG1 associated both with serum triglycerides (P = 5.36 × 10-9) and waist circumference (P = 5.21 × 10-9). The previously identified type 2 diabetes-associated locus cg08309687 in chromosome 21 associated with waist circumference for the first time (P = 2.24 × 10-7). Furthermore, a novel HDL association with cg17901584 in chromosome 1 was identified (P = 7.81 × 10-8). Our study supports previous genetic studies of MetS, finding that lipid metabolism plays a key role in pathology of the syndrome. We provide evidence regarding a close interplay with glucose metabolism. Finally, we suggest that in attempts to identify methylation loci linking separate MetS components, cg19693031 appears to represent a strong candidate.


Assuntos
Epigênese Genética/genética , Epigenômica/métodos , Síndrome Metabólica/genética , Membro 1 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/genética , Adulto , Idoso , Proteínas de Transporte/genética , Metilação de DNA/genética , Diabetes Mellitus Tipo 2/genética , Epigenoma/genética , Grupo com Ancestrais do Continente Europeu/genética , Feminino , Finlândia/epidemiologia , Genoma/genética , Estudo de Associação Genômica Ampla/métodos , Glucose/metabolismo , Humanos , Metabolismo dos Lipídeos/genética , Lipídeos/genética , Masculino , Síndrome Metabólica/metabolismo , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único/genética
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