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1.
Nat Commun ; 12(1): 4976, 2021 08 17.
Artigo em Inglês | MEDLINE | ID: mdl-34404790

RESUMO

To construct a superior microbial cell factory for chemical synthesis, a major challenge is to fully exploit cellular potential by identifying and engineering beneficial gene targets in sophisticated metabolic networks. Here, we take advantage of CRISPR interference (CRISPRi) and omics analyses to systematically identify beneficial genes that can be engineered to promote free fatty acids (FFAs) production in Escherichia coli. CRISPRi-mediated genetic perturbation enables the identification of 30 beneficial genes from 108 targets related to FFA metabolism. Then, omics analyses of the FFAs-overproducing strains and a control strain enable the identification of another 26 beneficial genes that are seemingly irrelevant to FFA metabolism. Combinatorial perturbation of four beneficial genes involving cellular stress responses results in a recombinant strain ihfAL--aidB+-ryfAM--gadAH-, producing 30.0 g L-1 FFAs in fed-batch fermentation, the maximum titer in E. coli reported to date. Our findings are of help in rewiring cellular metabolism and interwoven intracellular processes to facilitate high-titer production of biochemicals.


Assuntos
Escherichia coli/genética , Escherichia coli/isolamento & purificação , Escherichia coli/metabolismo , Ácidos Graxos não Esterificados/biossíntese , Sistemas CRISPR-Cas , Repetições Palindrômicas Curtas Agrupadas e Regularmente Espaçadas , Proteínas de Escherichia coli/genética , Proteínas de Escherichia coli/metabolismo , Ácidos Graxos/metabolismo , Fermentação , Regulação Bacteriana da Expressão Gênica , Engenharia Metabólica , Redes e Vias Metabólicas/genética , Transcriptoma
2.
J Agric Food Chem ; 69(34): 9813-9821, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34415766

RESUMO

ι-Carrageenan tetrasaccharide (ιCTs), a novel oligosaccharide, was hydrolyzed from ι-carrageenan with targeting marine tool-enzyme Cgi82A. Previously, we have found ιCTs exhibited a hypoglycemic effect, whether it could regulate lipid metabolism remains unknown. In this study, the insulin-resistant mice induced by high-fat-high-sucrose diet were orally administrated with ιCTs (30 mg/kg·bw) for 20 weeks. The results showed that the contents of triglyceride and cholesterol in both serum and liver were reduced by ιCTs, and their excretion in feces were promoted, suggesting lipid accumulation was inhibited. Intriguingly, the overall levels of bile acid in serum, liver, and feces were all raised by ιCTs. Given that bile acids are the essential signal factors for regulating lipid metabolism via the farnesoid-X-receptor (FXR), we conducted serum bile acid profile analysis and found that the levels of high-affinity agonists deoxycholic acid and lithocholic acid were decreased in the ιCTs group, showing that ιCTs failed to activate FXR. Western blot analysis showed that ιCTs downregulated hepatic FXR and small heterodimer partner (SHP) expression and increased downstream CYP7A1 expression via regulating the FXR-SHP signal to accelerate liver cholesterol conversion. Meanwhile, ιCTs decreased the expression of PXR and SREBP1c and elevated the expression of PPARα and CPT1α via regulating the FXR-PXR-SREBP1c/PPARα signal to inhibit fatty acid synthesis and promote fatty acid ß-oxidation. To the best of our knowledge, this study for the first time reported that ιCTs alleviated liver lipid accumulation via the bile acid-FXR-SHP/PXR signal to regulate cholesterol conversion and fatty acid metabolism, which highlighted a new idea for ameliorating insulin resistance.


Assuntos
Ácidos e Sais Biliares , Insulina , Animais , Ácidos e Sais Biliares/metabolismo , Carragenina , Colesterol/metabolismo , Colesterol 7-alfa-Hidroxilase/metabolismo , Ácidos Graxos/metabolismo , Insulina/metabolismo , Metabolismo dos Lipídeos , Fígado/metabolismo , Camundongos , Oligossacarídeos/metabolismo
3.
Int J Mol Sci ; 22(15)2021 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-34360931

RESUMO

Fatty acids (FAs) are of crucial importance for brain homeostasis and neural function. Glia cells support the high demand of FAs that the central nervous system (CNS) needs for its proper functioning. Additionally, FAs can modulate inflammation and direct CNS repair, thereby contributing to brain pathologies such Alzheimer's disease or multiple sclerosis. Intervention strategies targeting FA synthesis in glia represents a potential therapeutic opportunity for several CNS diseases.


Assuntos
Doenças do Sistema Nervoso Central/metabolismo , Sistema Nervoso Central , Ácidos Graxos/metabolismo , Neuroglia , Animais , Sistema Nervoso Central/metabolismo , Sistema Nervoso Central/patologia , Humanos , Neuroglia/metabolismo , Neuroglia/patologia
4.
Int J Mol Sci ; 22(15)2021 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-34361032

RESUMO

17,18-Epoxyeicosatetraenoic acid (17,18-EEQ) and 19,20-epoxydocosapentaenoic acid (19,20-EDP) are bioactive epoxides produced from n-3 polyunsaturated fatty acid eicosapentaenoic acid and docosahexaenoic acid, respectively. However, these epoxides are quickly metabolized into less active diols by soluble epoxide hydrolase (sEH). We have previously demonstrated that an sEH inhibitor, t-TUCB, decreased serum triglycerides (TG) and increased lipid metabolic protein expression in the brown adipose tissue (BAT) of diet-induced obese mice. This study investigates the preventive effects of t-TUCB (T) alone or combined with 19,20-EDP (T + EDP) or 17,18-EEQ (T + EEQ) on BAT activation in the development of diet-induced obesity and metabolic disorders via osmotic minipump delivery in mice. Both T + EDP and T + EEQ groups showed significant improvement in fasting glucose, serum triglycerides, and higher core body temperature, whereas heat production was only significantly increased in the T + EEQ group. Moreover, both the T + EDP and T + EEQ groups showed less lipid accumulation in the BAT. Although UCP1 expression was not changed, PGC1α expression was increased in all three treated groups. In contrast, the expression of CPT1A and CPT1B, which are responsible for the rate-limiting step for fatty acid oxidation, was only increased in the T + EDP and T + EEQ groups. Interestingly, as a fatty acid transporter, CD36 expression was only increased in the T + EEQ group. Furthermore, both the T + EDP and T + EEQ groups showed decreased inflammatory NFκB signaling in the BAT. Our results suggest that 17,18-EEQ or 19,20-EDP combined with t-TUCB may prevent high-fat diet-induced metabolic disorders, in part through increased thermogenesis, upregulating lipid metabolic protein expression, and decreasing inflammation in the BAT.


Assuntos
Fármacos Antiobesidade/uso terapêutico , Ácidos Araquidônicos/uso terapêutico , Benzoatos/uso terapêutico , Obesidade/tratamento farmacológico , Compostos de Fenilureia/uso terapêutico , Adipogenia , Tecido Adiposo Marrom/citologia , Tecido Adiposo Marrom/efeitos dos fármacos , Tecido Adiposo Marrom/metabolismo , Animais , Fármacos Antiobesidade/administração & dosagem , Fármacos Antiobesidade/farmacologia , Ácidos Araquidônicos/administração & dosagem , Ácidos Araquidônicos/farmacologia , Benzoatos/administração & dosagem , Benzoatos/farmacologia , Glicemia/metabolismo , Carnitina O-Palmitoiltransferase/metabolismo , Dieta Hiperlipídica , Epóxido Hidrolases/antagonistas & inibidores , Ácidos Graxos/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , NF-kappa B/metabolismo , Obesidade/etiologia , Obesidade/metabolismo , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo , Compostos de Fenilureia/administração & dosagem , Compostos de Fenilureia/farmacologia
5.
FASEB J ; 35(9): e21847, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34405464

RESUMO

Mounting evidence demonstrates that paternal diet programs offspring metabolism. However, the contribution of a pre-conception paternal high protein (HP) diet to offspring metabolism, gut microbiota, and epigenetic changes remains unclear. Here we show that paternal HP intake in Sprague Dawley rats programs protective metabolic outcomes in offspring. Compared to paternal high fat/sucrose (HF/S), HP diet improved body composition and insulin sensitivity and improved circulating satiety hormones and cecal short-chain fatty acids compared to HF/S and control diet (P < .05). Further, using 16S rRNA gene sequencing to assess gut microbial composition, we observed increased alpha diversity, distinct bacterial clustering, and increased abundance of Bifidobacterium, Akkermansia, Bacteroides, and Marvinbryantia in HP fathers and/or male and female adult offspring. At the epigenetic level, DNMT1and 3b expression was altered intergenerationally. Our study identifies paternal HP diet as a modulator of gut microbial composition, epigenetic markers, and metabolic function intergenerationally.


Assuntos
Composição Corporal , Dieta Rica em Proteínas , Epigênese Genética , Pai , Microbioma Gastrointestinal , Insulina/metabolismo , Exposição Paterna , Tecido Adiposo/metabolismo , Adiposidade , Envelhecimento , Animais , Peso Corporal , DNA (Citosina-5-)-Metiltransferases/metabolismo , Dieta Hiperlipídica , Sacarose na Dieta , Ingestão de Energia , Metabolismo Energético , Ácidos Graxos/metabolismo , Feminino , Fertilidade , Teste de Tolerância a Glucose , Hormônios/metabolismo , Resistência à Insulina , Fígado/metabolismo , Masculino , Tamanho do Órgão , Gravidez , Pequeno RNA não Traduzido/metabolismo , Ratos , Ratos Sprague-Dawley , Resposta de Saciedade , Desmame
6.
J Dairy Sci ; 104(9): 9868-9885, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34253360

RESUMO

Our objectives were to evaluate potential interactions in culture conditions that influence how exogenously dosed branched-chain VFA (BCVFA) would be recovered as elongated fatty acids (FA) or would affect bacterial populations. A 2 × 2 × 2 factorial arrangement of treatments evaluated 3 factors: (1) without versus with BCVFA (0 vs. 2 mmol/d each of isobutyrate, isovalerate, and 2-methylbutyrate; each dose was partially substituted with 13C-enriched tracers before and during the collection period); (2) high versus low pH (ranging diurnally from 6.3 to 6.8 vs. 5.7 to 6.2); and (3) low versus high particulate-phase passage rate (kp; 2.5 vs. 5.0%/h) in continuous cultures administered a 50:50 forage:concentrate diet twice daily. Samples of effluent were collected and composited before harvesting bacteria from which FA and DNA were extracted. Profiles and enrichments of FA in bacteria were evaluated by gas chromatography and isotope-ratio mass spectrometry. The 13C enrichment in bacterial FA was calculated as percentage recovery of dosed 13C-labeled BCVFA. Dosing BCVFA increased the even-chain iso-FA, preventing the reduced concentration at higher kp and potentially as a physiological response to decreased pH. However, decreasing pH decreased recovery of 13C in these even-chain FA, suggesting greater reliance on isobutyrate produced from degradation of dietary valine. The iso-FA were decreased, whereas anteiso-FA and 16:0 increased with decreasing pH. Thus, 2-methylbutyrate still appeared to be important as a precursor for anteiso-FA to counter the increased rigidity of bacterial membranes that had more saturated straight-chain FA when pH decreased. Provision of BCVFA stimulated the relative sequence abundance of Fibrobacter and Treponema, both of which require isobutyrate and 2-methylbutyrate. Numerous bacterial community members were shifted by low pH, including increased Prevotella and genera within the phylum Proteobacteria, at the expense of members within phylum Firmicutes. Because of relatively few interactions with pH and kp, supplementation of BCVFA can stimulate neutral detergent fiber degradability via key fibrolytic bacteria across a range of conditions. Decreasing pH shifted bacterial populations and their FA composition, suggesting that further research is needed to distinguish pH from dietary changes.


Assuntos
Ácidos Graxos , Rúmen , Ração Animal/análise , Animais , Detergentes/metabolismo , Dieta/veterinária , Digestão , Ácidos Graxos/metabolismo , Ácidos Graxos Voláteis/metabolismo , Fermentação , Cromatografia Gasosa-Espectrometria de Massas/veterinária , Concentração de Íons de Hidrogênio , Rúmen/metabolismo
7.
Artigo em Inglês | MEDLINE | ID: mdl-34252019

RESUMO

A Gram-stain-negative, aerobic, motile and rod-shaped novel bacterial strain, designated MAH-29T, was isolated from rhizospheric soil of a persimmon tree. The colonies were light pink coloured, smooth, spherical and 0.1-0.8 mm in diameter when grown on Reasoner's 2A (R2A) agar for 2 days. Strain MAH-29T was able to grow at 20-37 °C, at pH 5.0-8.5 and at 0-2.0 % NaCl. Cell growth occurred on nutrient agar and R2A agar. The strain was positive in both oxidase and catalase tests. According to the 16S rRNA gene sequence comparisons, the isolate was identified as a member of the genus Niastella and was closely related to Niastella vici DJ57T (97.7 % similarity), Niastella koreensis GR20-10T (97.1 %) and Niastella yeongjuensis GR20-13T (97.0 %). Strain MAH-29T has a draft genome size of 8 876 333 bp (31 contigs), annotated with 6920 protein-coding genes, 61 tRNA and four rRNA genes. The average nucleotide identity and digital DNA-DNA hybridization values between strain MAH-29T and three closely related type strains were in the range of 78.2-83.2 % and 22.1-27.0 %, respectively. The genomic DNA G+C content was 43.8 mol%. The predominant isoprenoid quinone was menaquinone 7. The major fatty acids were identified as iso-C15:0, iso-C15:1 G and iso-C17:0 3OH. On the basis of DNA-DNA hybridization results, genotypic analysis and chemotaxonomic and physiological data, strain MAH-29T represents a novel species within the genus Niastella, for which the name Niastella soli sp. nov. is proposed, with MAH-29T (=KACC 19969T=CGMCC 1.16606T) as the type strain.


Assuntos
Bacteroidetes/classificação , Diospyros/microbiologia , Filogenia , Microbiologia do Solo , Técnicas de Tipagem Bacteriana , Bacteroidetes/isolamento & purificação , Composição de Bases , DNA Bacteriano/genética , Ácidos Graxos/metabolismo , Hibridização de Ácido Nucleico , Pigmentação , RNA Ribossômico 16S/genética , Rizosfera , Árvores/microbiologia , Vitamina K 2/análogos & derivados , Vitamina K 2/química
8.
Arterioscler Thromb Vasc Biol ; 41(9): 2387-2398, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34320835

RESUMO

Objective: CD4 T cells are important regulators of atherosclerotic progression. The metabolic profile of CD4 T cells controls their signaling and function, but how atherosclerosis affects T-cell metabolism is unknown. Here, we sought to determine the impact of atherosclerosis on CD4 T-cell metabolism and the contribution of such metabolic alterations to atheroprogression. Approach and Results: Using PCR arrays, we profiled the expression of metabolism genes in CD4 T cells from atherosclerotic apolipoprotein-E knockout mice fed a Western diet. These cells exhibited dysregulated expression of genes critically involved in glycolysis and fatty acid degradation, compared with those from animals fed a standard laboratory diet. We examined how T-cell metabolism was changed in either Western diet­fed apolipoprotein-E knockout mice or samples from patients with cardiovascular disease by measuring glucose uptake, activation, and proliferation in CD4 T cells. We found that naive CD4 T cells from Western diet­fed apolipoprotein-E knockout mice failed to uptake glucose and displayed impaired proliferation and activation, compared with CD4 T cells from standard laboratory diet­fed animals. Similarly, we observed that naive CD4 T-cell frequencies were reduced in the circulation of human subjects with high cardiovascular disease compared with low cardiovascular disease. Naive T cells from high cardiovascular disease subjects also showed reduced proliferative capacity. Conclusions: These results highlight the dysfunction that occurs in CD4 T-cell metabolism and immune responses during atherosclerosis. Targeting metabolic pathways within naive CD4 T cells could thus yield novel therapeutic approaches for improving CD4 T-cell responses against atheroprogression.


Assuntos
Aterosclerose/metabolismo , Linfócitos T CD4-Positivos/metabolismo , Glicólise , Placa Aterosclerótica , Idoso , Animais , Aterosclerose/genética , Aterosclerose/imunologia , Aterosclerose/patologia , Contagem de Linfócito CD4 , Linfócitos T CD4-Positivos/imunologia , Proliferação de Células , Células Cultivadas , Dieta Ocidental , Modelos Animais de Doenças , Ácidos Graxos/metabolismo , Feminino , Regulação da Expressão Gênica , Glicólise/genética , Humanos , Ativação Linfocitária , Masculino , Camundongos Endogâmicos C57BL , Camundongos Knockout para ApoE , Pessoa de Meia-Idade , Oxirredução , Fenótipo
9.
Molecules ; 26(13)2021 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-34279376

RESUMO

As microalgae are producers of proteins, lipids, polysaccharides, pigments, vitamins and unique secondary metabolites, microalgal biotechnology has gained attention in recent decades. Microalgae can be used for biomass production and to obtain biotechnologically important products. Here, we present the application of a method of producing a natural, biologically active composite obtained from unicellular microalgae of the genus Planktochlorella sp. as a modulator of the growth of microorganisms that can be used in the cosmetics and pharmaceutical industries by exploiting the phenomenon of photo-reprogramming of metabolism. The combination of red and blue light allows the collection of biomass with unique biochemical profiles, especially fatty acid composition (Patent Application P.429620). The ethanolic and water extracts of algae biomass inhibited the growth of a number of pathogenic bacteria, namely Enterococcus faecalis, Staphylococcus aureus PCM 458, Streptococcus pyogenes PCM 2318, Pseudomonas aeruginosa, Escherichia coli PCM 2209 and Candida albicans ATCC 14053. The algal biocomposite obtained according to our procedure can be used also as a prebiotic supplement. The presented technology may allow the limitation of the use of antibiotics and environmentally harmful chemicals commonly used in preparations against Enterococcus faecalis, Staphylococcus aureus, Streptococcus pyogenes, Pseudomonas aeruginosa, Escherichia coli or Candida spp.


Assuntos
Anti-Infecciosos/farmacologia , Biomassa , Clorófitas/metabolismo , Extratos Vegetais/farmacologia , Candida albicans/efeitos dos fármacos , Clorófitas/química , Clorófitas/efeitos da radiação , Enterococcus faecalis/efeitos dos fármacos , Ácidos Graxos/metabolismo , Luz , Engenharia Metabólica/métodos , Staphylococcus aureus/efeitos dos fármacos , Streptococcus pyogenes/efeitos dos fármacos
10.
Fish Physiol Biochem ; 47(4): 1243-1255, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34226986

RESUMO

The effects of stocking density on growth performance, serum biochemistry, digestive enzymes, immune response, and muscle quality of largemouth bass (Micropterus salmoides) reared in nine in-pond raceway systems (IPRS, 22.0 m × 5.0 m × 2.0 m) were studied. M. salmoides with initial an body weight of 8.25 ± 0.51 g and body length of 6.99 ± 0.44 cm were reared at an initial stocking density of 90.91 ind./m3 (low stocking density, LSD), 113.63 ind./m3 (middle stocking density, MSD), and 136.36 ind./m3 (high stocking density, HSD) with triplication. After 300 days of culture, MSD recorded the highest final body weight, weight gain, specific growth rate, and yield, but the food conversion ratio in MSD was the lowest. The viscerosomatic index in LSD was significantly higher than other groups. The fish serum reared at HSD showed significantly lower total protein, higher total cholesterol, triglyceride, total bilirubin, glucose content, alanine transaminase, and aspartate transaminase activity. Significantly lower intestinal amylase, lipase, trypsin activities, hepatic superoxide dismutase (SOD) and catalase (CAT) activities, and higher malondialdehyde content were detected in HSD compared to others. The content of crude lipid, saturated fatty acid decreased, and total essential amino acid, delicious amino acid, and polyunsaturated fatty acid increased in muscle with stocking density increase. No significant difference was observed in muscle texture. Profitability analysis indicated the benefit-to-cost ratio varied between 1.10 and 1.68, of which MSD was significantly higher than others. The optimal stocking density for M. salmoides should be 113.63 ind./m3 in an IPRS farm.


Assuntos
Aquicultura/métodos , Bass , Alanina Transaminase/sangue , Aminoácidos/metabolismo , Amilases/metabolismo , Animais , Aspartato Aminotransferases/sangue , Bass/sangue , Bass/crescimento & desenvolvimento , Bass/imunologia , Bass/metabolismo , Catalase/metabolismo , Ácidos Graxos/metabolismo , Proteínas de Peixes/sangue , Imunidade , Intestinos/enzimologia , Lipase/metabolismo , Fígado/metabolismo , Músculos/química , Esteróis/sangue , Superóxido Dismutase/metabolismo , Triglicerídeos/sangue , Tripsina/metabolismo
11.
Int J Mol Sci ; 22(14)2021 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-34298967

RESUMO

Pathological fibrosis of the liver is a landmark feature in chronic liver diseases, including nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH). Diagnosis and assessment of progress or treatment efficacy today requires biopsy of the liver, which is a challenge in, e.g., longitudinal interventional studies. Molecular imaging techniques such as positron emission tomography (PET) have the potential to enable minimally invasive assessment of liver fibrosis. This review will summarize and discuss the current status of the development of innovative imaging markers for processes relevant for fibrogenesis in liver, e.g., certain immune cells, activated fibroblasts, and collagen depositions.


Assuntos
Imagem Molecular/tendências , Hepatopatia Gordurosa não Alcoólica/diagnóstico por imagem , Alarminas/metabolismo , Animais , Aquaporinas/análise , Colágeno/análise , Meios de Contraste , Citocinas/metabolismo , Técnicas de Imagem por Elasticidade/métodos , Endopeptidases/análise , Ácidos Graxos/metabolismo , Fibroblastos/química , Fibroblastos/ultraestrutura , Radioisótopos de Flúor , Radioisótopos de Gálio , Células Estreladas do Fígado/química , Células Estreladas do Fígado/ultraestrutura , Hepatócitos/metabolismo , Humanos , Cirrose Hepática/diagnóstico por imagem , Cirrose Hepática/etiologia , Cirrose Hepática/metabolismo , Proteínas de Membrana/análise , Camundongos , Imagem Molecular/métodos , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/metabolismo , Tomografia por Emissão de Pósitrons/métodos , Compostos Radiofarmacêuticos , Ratos , Receptores CCR2/análise , Triglicerídeos/metabolismo
12.
Int J Mol Sci ; 22(14)2021 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-34298981

RESUMO

Peroxisome proliferator-activated receptors (PPARs) are nuclear hormone receptors expressed in the skin. Three PPAR isotypes, α (NRC1C1), ß or δ (NRC1C2) and γ (NRC1C3), have been identified. After activation through ligand binding, PPARs heterodimerize with the 9-cis-retinoic acid receptor (RXR), another nuclear hormone receptor, to bind to specific PPAR-responsive elements in regulatory regions of target genes mainly involved in organogenesis, cell proliferation, cell differentiation, inflammation and metabolism of lipids or carbohydrates. Endogenous PPAR ligands are fatty acids and fatty acid metabolites. In past years, much emphasis has been given to PPARα and γ in skin diseases. PPARß/δ is the least studied PPAR family member in the skin despite its key role in several important pathways regulating inflammation, keratinocyte proliferation and differentiation, metabolism and the oxidative stress response. This review focuses on the role of PPARß/δ in keratinocytes and its involvement in psoriasis and atopic dermatitis. Moreover, the relevance of targeting PPARß/δ to alleviate skin inflammation is discussed.


Assuntos
Dermatite Atópica/metabolismo , Queratinócitos/metabolismo , PPAR delta/fisiologia , Psoríase/metabolismo , Pele/metabolismo , Anaerobiose , Animais , Dimerização , Eicosanoides/metabolismo , Ácidos Graxos/metabolismo , Glicólise , Humanos , Camundongos , Camundongos Mutantes , Especificidade de Órgãos , Fosforilação , Isoformas de Proteínas/fisiologia , Processamento de Proteína Pós-Traducional , Proteólise , Receptores X de Retinoides/metabolismo , Pele/patologia
13.
Int J Mol Sci ; 22(13)2021 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-34209706

RESUMO

The plant transcription factor WRINKLED1 (WRI1), a member of AP2/EREBP, is involved in the regulation of glycolysis and the expression of genes related to the de novo synthesis of fatty acids in plastids. In this study, the key regulator of seed oil synthesis and accumulation transcription factor gene PoWRI1 was identified and cloned, having a complete open reading frame of 1269 bp and encoding 422 amino acids. Subcellular localization analysis showed that PoWRI1 is located at the nucleus. After the expression vector of PoWRI1 was constructed and transformed into wild-type Arabidopsis thaliana, it was found that the overexpression of PoWRI1 increased the expression level of downstream target genes such as BCCP2, KAS1, and PKP-ß1. As a result, the seeds of transgenic plants became larger, the oil content increased significantly, and the unsaturated fatty acid content increased, which provide a scientific theoretical basis for the subsequent use of genetic engineering methods to improve the fatty acid composition and content of plant seeds.


Assuntos
Regulação da Expressão Gênica de Plantas , Paeonia/genética , Paeonia/metabolismo , Óleos Vegetais/metabolismo , Proteínas de Plantas/genética , Arabidopsis/genética , Arabidopsis/metabolismo , Sequência de Bases , Vias Biossintéticas/genética , Clonagem Molecular , Ácidos Graxos/metabolismo , Fenótipo , Filogenia , Proteínas de Plantas/metabolismo , Plantas Geneticamente Modificadas , Transporte Proteico , Sementes/genética , Sementes/metabolismo , Análise de Sequência de DNA
14.
Mol Cell ; 81(13): 2686-2687, 2021 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-34214442

RESUMO

Liu et al. (2021) demonstrate that CHKα2 is capable of promoting lipolysis of lipid droplets through mechanisms that require sequential steps of post-translational modifications after glucose deprivation. Intriguingly, the oxidation of fatty acids derived from lipid droplets is essential for the survival of tumor cells that informs clinical outcome among glioblastoma patients.


Assuntos
Glioblastoma , Lipólise , Ácidos Graxos/metabolismo , Glioblastoma/genética , Glioblastoma/metabolismo , Humanos , Gotículas Lipídicas/metabolismo , Oxirredução
15.
Int J Mol Sci ; 22(13)2021 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-34199035

RESUMO

Non-alcoholic fatty liver disease (NAFLD) is a major public health problem worldwide. NAFLD (both simple steatosis and steatohepatitis) is characterized by alterations in hepatic lipid metabolism, which may lead to the development of severe liver complications including cirrhosis and hepatocellular carcinoma. Thus, an exhaustive examination of lipid disorders in the liver of NAFLD patients is much needed. Mass spectrometry-based lipidomics platforms allow for in-depth analysis of lipid alterations in a number of human diseases, including NAFLD. This review summarizes the current research on lipid alterations associated with NAFLD and related complications, with special emphasis on the changes in long-chain and short-chain fatty acids levels in both serum and liver tissue, as well as in the hepatic expression of genes encoding the enzymes catalyzing lipid interconversions.


Assuntos
Suscetibilidade a Doenças , Ácidos Graxos/metabolismo , Hepatopatia Gordurosa não Alcoólica/metabolismo , Hepatopatia Gordurosa não Alcoólica/patologia , Animais , Biomarcadores , Carcinoma Hepatocelular/etiologia , Carcinoma Hepatocelular/metabolismo , Progressão da Doença , Ácidos Graxos/sangue , Ácidos Graxos/química , Microbioma Gastrointestinal , Regulação da Expressão Gênica , Humanos , Metabolismo dos Lipídeos , Lipidômica/métodos , Neoplasias Hepáticas/etiologia , Neoplasias Hepáticas/metabolismo , Estrutura Molecular , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/etiologia
16.
BMC Plant Biol ; 21(1): 348, 2021 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-34301189

RESUMO

BACKGROUND: The oil-tea tree (Camellia oleifera Abel.) is a woody tree species that produces edible oil in the seed. C. oleifera oil has high nutritional value and is also an important raw material for medicine and cosmetics. In China, due to the uncertainty on maturity period and oil synthesis mechanism of many C. oleifera cultivars, growers may harvest fruits prematurely, which could not maximize fruit and oil yields. In this study, our objective was to explore the mechanism and differences of oil synthesis between two Camellia oleifera cultivars for a precise definition of the fruit ripening period and the selection of appropriate cultivars. RESULTS: The results showed that 'Huashuo' had smaller fruits and seeds, lower dry seed weight and lower expression levels of fatty acid biosynthesis genes in July. We could not detect the presence of oil and oil bodies in 'Huashuo' seeds until August, and oil and oil bodies were detected in 'Huajin' seeds in July. Moreover, 'Huashuo' seeds were not completely blackened in October with up to 60.38% of water and approximately 37.98% of oil in seed kernels whose oil content was much lower than normal mature seed kernels. The oil bodies in seed endosperm cells of 'Huajin' were always higher than those of 'Huashuo' from July to October. CONCLUSION: Our results confirmed that C. oleifera 'Huashuo' fruits matured at a lower rate compared to 'Huajin' fruits and that 'Huajin' seeds entered the oil synthesis period earlier than 'Huashuo' seeds. Moreover, 'Huashuo' fruits did not mature during the Frost's Descent period (October 23-24 each year).


Assuntos
Camellia/crescimento & desenvolvimento , Camellia/genética , Camellia/metabolismo , Frutas/crescimento & desenvolvimento , Frutas/genética , Frutas/metabolismo , Óleos Vegetais/metabolismo , China , Produtos Agrícolas/genética , Produtos Agrícolas/crescimento & desenvolvimento , Produtos Agrícolas/metabolismo , Ácidos Graxos/metabolismo , Variação Genética , Genótipo , Melhoramento Vegetal , Plantas Medicinais/genética , Plantas Medicinais/crescimento & desenvolvimento , Plantas Medicinais/metabolismo , Transcriptoma
17.
Artigo em Inglês | MEDLINE | ID: mdl-34300048

RESUMO

Due to the need for continuous work, the heart uses up to 8% of the total energy expenditure. Due to the relatively low adenosine triphosphate (ATP) storage capacity, the heart's work is dependent on its production. This is possible due to the metabolic flexibility of the heart, which allows it to use numerous substrates as a source of energy. Under normal conditions, a healthy heart obtains approximately 95% of its ATP by oxidative phosphorylation in the mitochondria. The primary source of energy is fatty acid oxidation, the rest of the energy comes from the oxidation of pyruvate. A failed heart is characterised by a disturbance in these proportions, with the contribution of individual components as a source of energy depending on the aetiology and stage of heart failure. A unique form of cardiac dysfunction is sepsis-induced cardiomyopathy, characterised by a significant reduction in energy production and impairment of cardiac oxidation of both fatty acids and glucose. Metabolic disorders appear to contribute to the pathogenesis of cardiac dysfunction and therefore are a promising target for future therapies. However, as many aspects of the metabolism of the failing heart remain unexplained, this issue requires further research.


Assuntos
Cardiomiopatias , Insuficiência Cardíaca , Sepse , Trifosfato de Adenosina , Cardiomiopatias/etiologia , Cardiomiopatias/metabolismo , Metabolismo Energético , Ácidos Graxos/metabolismo , Glucose/metabolismo , Coração , Insuficiência Cardíaca/etiologia , Humanos , Miocárdio/metabolismo , Oxirredução
18.
Nat Commun ; 12(1): 4590, 2021 07 28.
Artigo em Inglês | MEDLINE | ID: mdl-34321466

RESUMO

Covalent attachment of C16:0 to proteins (palmitoylation) regulates protein function. Proteins are also S-acylated by other fatty acids including C18:0. Whether protein acylation with different fatty acids has different functional outcomes is not well studied. We show here that C18:0 (stearate) and C18:1 (oleate) compete with C16:0 to S-acylate Cys3 of GNAI proteins. C18:0 becomes desaturated so that C18:0 and C18:1 both cause S-oleoylation of GNAI. Exposure of cells to C16:0 or C18:0 shifts GNAI acylation towards palmitoylation or oleoylation, respectively. Oleoylation causes GNAI proteins to shift out of cell membrane detergent-resistant fractions where they potentiate EGFR signaling. Consequently, exposure of cells to C18:0 reduces recruitment of Gab1 to EGFR and reduces AKT activation. This provides a molecular mechanism for the anti-tumor effects of C18:0, uncovers a mechanistic link how metabolites affect cell signaling, and provides evidence that the identity of the fatty acid acylating a protein can have functional consequences.


Assuntos
Subunidades alfa Gi-Go de Proteínas de Ligação ao GTP/metabolismo , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Transdução de Sinais/fisiologia , Ácidos Esteáricos/metabolismo , Acilação , Membrana Celular/metabolismo , Proliferação de Células , Ácidos Graxos/metabolismo , Subunidades alfa Gi-Go de Proteínas de Ligação ao GTP/genética , Humanos , Lipoilação , Células MCF-7 , Ácidos Oleicos/metabolismo
19.
Nat Commun ; 12(1): 4368, 2021 07 16.
Artigo em Inglês | MEDLINE | ID: mdl-34272383

RESUMO

Bioproduction of renewable chemicals is considered as an urgent solution for fossil energy crisis. However, despite tremendous efforts, it is still challenging to generate microbial strains that can produce target biochemical to high levels. Here, we report an example of biosynthesis of high-value and easy-recoverable derivatives built upon natural microbial pathways, leading to improvement in bioproduction efficiency. By leveraging pathways in solventogenic clostridia for co-producing acyl-CoAs, acids and alcohols as precursors, through rational screening for host strains and enzymes, systematic metabolic engineering-including elimination of putative prophages, we develop strains that can produce 20.3 g/L butyl acetate and 1.6 g/L butyl butyrate. Techno-economic analysis results suggest the economic competitiveness of our developed bioprocess. Our principles of selecting the most appropriate host for specific bioproduction and engineering microbial chassis to produce high-value and easy-separable end products may be applicable to other bioprocesses.


Assuntos
Acetatos/metabolismo , Butiratos/química , Clostridium/metabolismo , Ácidos Graxos/metabolismo , Fermentação/genética , Engenharia Metabólica/métodos , Acetilcoenzima A/metabolismo , Biocombustíveis/microbiologia , Biomassa , Clostridium/enzimologia , Clostridium/genética , Ésteres/metabolismo , Redes e Vias Metabólicas/genética , NAD/metabolismo , Proteínas/genética , Proteínas/metabolismo , Proteínas Recombinantes
20.
Nat Commun ; 12(1): 4362, 2021 07 16.
Artigo em Inglês | MEDLINE | ID: mdl-34272396

RESUMO

Squamous cell carcinomas (SCCs) comprise one of the most common histologic types of human cancer. Transcriptional dysregulation of SCC cells is orchestrated by tumor protein p63 (TP63), a master transcription factor (TF) and a well-researched SCC-specific oncogene. In the present study, both Gene Set Enrichment Analysis (GSEA) of SCC patient samples and in vitro loss-of-function assays establish fatty-acid metabolism as a key pathway downstream of TP63. Further studies identify sterol regulatory element binding transcription factor 1 (SREBF1) as a central mediator linking TP63 with fatty-acid metabolism, which regulates the biosynthesis of fatty-acids, sphingolipids (SL), and glycerophospholipids (GPL), as revealed by liquid chromatography tandem mass spectrometry (LC-MS/MS)-based lipidomics. Moreover, a feedback co-regulatory loop consisting of SREBF1/TP63/Kruppel like factor 5 (KLF5) is identified, which promotes overexpression of all three TFs in SCCs. Downstream of SREBF1, a non-canonical, SCC-specific function is elucidated: SREBF1 cooperates with TP63/KLF5 to regulate hundreds of cis-regulatory elements across the SCC epigenome, which converge on activating cancer-promoting pathways. Indeed, SREBF1 is essential for SCC viability and migration, and its overexpression is associated with poor survival in SCC patients. Taken together, these data shed light on mechanisms of transcriptional dysregulation in cancer, identify specific epigenetic regulators of lipid metabolism, and uncover SREBF1 as a potential therapeutic target and prognostic marker in SCC.


Assuntos
Carcinoma de Células Escamosas/metabolismo , Neoplasias Esofágicas/metabolismo , Neoplasias de Cabeça e Pescoço/metabolismo , Fatores de Transcrição Kruppel-Like/metabolismo , Metabolismo dos Lipídeos/genética , Neoplasias Pulmonares/metabolismo , Proteína de Ligação a Elemento Regulador de Esterol 1/metabolismo , Fatores de Transcrição/metabolismo , Proteínas Supressoras de Tumor/metabolismo , Acetilação , Carcinoma de Células Escamosas/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Sequenciamento de Cromatina por Imunoprecipitação , Cromatografia Líquida , Epigenômica , Receptores ErbB/genética , Receptores ErbB/metabolismo , Neoplasias Esofágicas/genética , Ácidos Graxos/biossíntese , Ácidos Graxos/metabolismo , Regulação Neoplásica da Expressão Gênica , Neoplasias de Cabeça e Pescoço/genética , Histonas/metabolismo , Humanos , Fatores de Transcrição Kruppel-Like/genética , Neoplasias Pulmonares/genética , Elementos Reguladores de Transcrição , Transdução de Sinais/genética , Esfingolipídeos/biossíntese , Esfingolipídeos/metabolismo , Proteína de Ligação a Elemento Regulador de Esterol 1/genética , Serina-Treonina Quinases TOR/genética , Serina-Treonina Quinases TOR/metabolismo , Espectrometria de Massas em Tandem , Fatores de Transcrição/genética , Transcriptoma/genética , Proteínas Supressoras de Tumor/genética
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