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2.
Molecules ; 26(4)2021 Feb 12.
Artículo en Inglés | MEDLINE | ID: mdl-33673308

RESUMEN

The use of adequate thermal energy storage (TES) systems is an efficient way to achieve thermal comfort in buildings reducing the cooling and heating demand. Besides, deploy phase change materials (PCM) to meet and enhance the TES needs is highly effective and widely studied. In this paper, a study of the degradation of two fatty acids is presented, capric and myristic acids, in order to evaluate whether their thermo-physical properties are affected throughout time during service. This was carried out by means of two different types of thermal treatments: degradation at constant temperature (thermal stability test), 60 °C during 100 h and 500 h, and degradation with heating and cooling cycling (thermal cycling stability), between a temperature range from 15 °C to 70 °C with 0.5 °C/min ramp during 500 and 1000 cycles. Despite no significant changes were measured for myristic acid, experimental results revealed a decrease of melting enthalpy of 6.6% in capric acid thermally treated for 500 h. Evidences of chemical degradation were found that might explain the decrease in thermophysical properties during use.


Asunto(s)
Transferencia de Energía , Ácidos Grasos/química , Termodinámica , Ácidos Grasos/metabolismo , Calefacción , Calor , Transición de Fase , Temperatura
3.
Int J Mol Sci ; 22(4)2021 Feb 17.
Artículo en Inglés | MEDLINE | ID: mdl-33671212

RESUMEN

Lysophosphatidic acid (LPA) species are a family of bioactive lipids that transmit signals via six cognate G protein-coupled receptors, which are required for brain development and function of the nervous system. LPA affects the function of all cell types in the brain and can display beneficial or detrimental effects on microglia function. During earlier studies we reported that LPA treatment of microglia induces polarization towards a neurotoxic phenotype. In the present study we investigated whether these alterations are accompanied by the induction of a specific immunometabolic phenotype in LPA-treated BV-2 microglia. In response to LPA (1 µM) we observed slightly decreased mitochondrial respiration, increased lactate secretion and reduced ATP/ADP ratios indicating a switch towards aerobic glycolysis. Pathway analyses demonstrated induction of the Akt-mTOR-Hif1α axis under normoxic conditions. LPA treatment resulted in dephosphorylation of AMP-activated kinase, de-repression of acetyl-CoA-carboxylase and increased fatty acid content in the phospholipid and triacylglycerol fraction of BV-2 microglia lipid extracts, indicating de novo lipogenesis. LPA led to increased intracellular amino acid content at one or more time points. Finally, we observed LPA-dependent generation of reactive oxygen species (ROS), phosphorylation of nuclear factor erythroid 2-related factor 2 (Nrf2), upregulated protein expression of the Nrf2 target regulatory subunit of glutamate-cysteine ligase and increased glutathione synthesis. Our observations suggest that LPA, as a bioactive lipid, induces subtle alterations of the immunometabolic program in BV-2 microglia.


Asunto(s)
Aminoácidos/metabolismo , Glucólisis/efectos de los fármacos , Lipogénesis/efectos de los fármacos , Lisofosfolípidos/farmacología , Microglía/metabolismo , Nucleótidos de Adenina/metabolismo , Aerobiosis/efectos de los fármacos , Animales , Antioxidantes/metabolismo , Línea Celular , Respiración de la Célula/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Metabolismo Energético/efectos de los fármacos , Ácidos Grasos/metabolismo , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Ácido Láctico/metabolismo , Redes y Vías Metabólicas/efectos de los fármacos , Ratones , Microglía/efectos de los fármacos , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Modelos Biológicos , Factor 2 Relacionado con NF-E2/metabolismo , Fosfocreatina/metabolismo , Fosforilación/efectos de los fármacos , Proteínas Proto-Oncogénicas c-akt/metabolismo , Serina-Treonina Quinasas TOR/metabolismo
4.
Animal ; 15(2): 100118, 2021 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-33712216

RESUMEN

Immunocastrated pigs (IC) exhibit intensive fat deposition after immunisation, but the underlying mechanisms of intensified fat metabolism and deposition are not yet fully understood. Moreover, there is also a lack of comparative studies performed on IC, entire males (EM) and surgical castrates (SC). The main objective of our research was, therefore, to characterise the adipose tissue from the quantitative, histo-morphological and biochemical perspectives in IC 5 weeks after their immunisation in comparison to EM and SC. Immunocastrated pigs had an intermediate position in carcass fatness traits between EM (the leanest) and SC (the fattest). The histo-morphological traits of the subcutaneous adipose tissue of IC were similar to those of SC and differed from those of EM; i.e., they exhibited larger adipocytes in the outer backfat and a larger lobulus surface area in both backfat layers than EM. Intensive fat tissue development in IC was corroborated with higher activities of lipogenic enzymes (i.e., fatty acid synthase, malic enzyme, glucose 6-phosphate dehydrogenase, citrate cleavage enzyme), which was especially pronounced in the subcutaneous adipose tissue of IC (1.5- to 2.7-fold higher activity than in EM or SC). The fatty acid composition of the backfat in IC was similar to that in EM pigs. Both IC and EM exhibited less saturated and more polyunsaturated fatty acids than SC. In contrast, the fatty acid composition of the intramuscular fat of longissimus dorsi muscle in IC pigs was more similar to SC than to EM (higher monounsaturated and lower polyunsaturated fatty acid content in IC and SC than EM). In this study, it was demonstrated that immunocastration notably influenced lipid metabolism. This was shown by increased quantity of lipid depots and with changes in adipose tissue cellularity compared to EM, with changes in the fatty acid composition of the intramuscular fat and enhanced lipogenic activity compared to both EM and SC. These results provide new insights into the specificity of adipose tissue development and deposition in IC compared to EM and SC.


Asunto(s)
Tejido Adiposo , Composición Corporal , Tejido Adiposo/metabolismo , Animales , Ácidos Grasos/metabolismo , Metabolismo de los Lípidos , Lipogénesis , Masculino , Porcinos
5.
Nat Metab ; 3(2): 244-257, 2021 02.
Artículo en Inglés | MEDLINE | ID: mdl-33619378

RESUMEN

Obesity is a global epidemic leading to increased mortality and susceptibility to comorbidities, with few viable therapeutic interventions. A hallmark of disease progression is the ectopic deposition of lipids in the form of lipid droplets in vital organs such as the liver. However, the mechanisms underlying the dynamic storage and processing of lipids in peripheral organs remain an outstanding question. Here, we show an unexpected function for the major cap-binding protein, eIF4E, in high-fat-diet-induced obesity. In response to lipid overload, select networks of proteins involved in fat deposition are altered in eIF4E-deficient mice. Specifically, distinct messenger RNAs involved in lipid metabolic processing and storage pathways are enhanced at the translation level by eIF4E. Failure to translationally upregulate these mRNAs results in increased fatty acid oxidation, which enhances energy expenditure. We further show that inhibition of eIF4E phosphorylation genetically-and by a potent clinical compound-restrains weight gain following intake of a high-fat diet. Together, our study uncovers translational control of lipid processing as a driver of high-fat-diet-induced weight gain and provides a pharmacological target to treat obesity.


Asunto(s)
Adipogénesis/genética , Dieta Alta en Grasa , Factor 4E Eucariótico de Iniciación/genética , Factor 4E Eucariótico de Iniciación/metabolismo , Metabolismo de los Lípidos/genética , Obesidad/genética , Adipocitos/patología , Animales , Metabolismo Energético , Ácidos Grasos/metabolismo , Gotas Lipídicas , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Obesidad/patología , Oxidación-Reducción , Fosforilación , ARN Mensajero/biosíntesis , ARN Mensajero/genética
6.
Int J Mol Sci ; 22(3)2021 Feb 02.
Artículo en Inglés | MEDLINE | ID: mdl-33540894

RESUMEN

Heart failure remains the most common cause of death in the industrialized world. In spite of new therapeutic interventions that are constantly being developed, it is still not possible to completely protect against heart failure development and progression. This shows how much more research is necessary to understand the underlying mechanisms of this process. In this review, we give a detailed overview of the contribution of impaired mitochondrial dynamics and energy homeostasis during heart failure progression. In particular, we focus on the regulation of fatty acid metabolism and the effects of fatty acid accumulation on mitochondrial structural and functional homeostasis.


Asunto(s)
Ácidos Grasos/metabolismo , Insuficiencia Cardíaca/metabolismo , Mitocondrias Cardíacas/metabolismo , Dinámicas Mitocondriales , Tejido Adiposo/metabolismo , Señalización del Calcio , Cardiomiopatías/metabolismo , Ceramidas/biosíntesis , Ciclo del Ácido Cítrico , Progresión de la Enfermedad , Ácidos Grasos/efectos adversos , Homeostasis , Humanos , Cuerpos Cetónicos/metabolismo , Enfermedades Mitocondriales/metabolismo , Mitofagia , NAD/metabolismo , Pericardio/metabolismo , Receptores Activados del Proliferador del Peroxisoma/fisiología , Proteínas Proto-Oncogénicas c-bcl-2/fisiología , Especies Reactivas de Oxígeno/metabolismo
7.
Int J Mol Sci ; 22(3)2021 Jan 26.
Artículo en Inglés | MEDLINE | ID: mdl-33530558

RESUMEN

Molecular dynamics (MD) simulations of uncoupling proteins (UCP), a class of transmembrane proteins relevant for proton transport across inner mitochondrial membranes, represent a complicated task due to the lack of available structural data. In this work, we use a combination of homology modelling and subsequent microsecond molecular dynamics simulations of UCP2 in the DOPC phospholipid bilayer, starting from the structure of the mitochondrial ATP/ADP carrier (ANT) as a template. We show that this protocol leads to a structure that is impermeable to water, in contrast to MD simulations of UCP2 structures based on the experimental NMR structure. We also show that ATP binding in the UCP2 cavity is tight in the homology modelled structure of UCP2 in agreement with experimental observations. Finally, we corroborate our results with conductance measurements in model membranes, which further suggest that the UCP2 structure modeled from ANT protein possesses additional key functional elements, such as a fatty acid-binding site at the R60 region of the protein, directly related to the proton transport mechanism across inner mitochondrial membranes.


Asunto(s)
Proteínas Mitocondriales/química , Simulación de Dinámica Molecular , Conformación Proteica , Proteína Desacopladora 2/química , Adenosina Trifosfato/química , Adenosina Trifosfato/metabolismo , Secuencia de Aminoácidos , Animales , Ácidos Grasos/química , Ácidos Grasos/metabolismo , Transporte Iónico , Proteínas de la Membrana/química , Ratones , Proteínas Mitocondriales/metabolismo , Unión Proteica , Estabilidad Proteica , Relación Estructura-Actividad , Proteína Desacopladora 2/metabolismo
8.
Life Sci ; 272: 119242, 2021 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-33607155

RESUMEN

AIMS: Recent studies have shown that enhancement of fatty acid utilization through feeding animals a high fat diet (HFD) attenuated cardiac dysfunction in heart failure (HF). Here, we aimed to examine the temporal effects of HFD feeding on cardiac function in mice with heart failure and its underlying mechanism. MAIN METHODS: Pressure overload-induced HF was established via transverse aortic constriction (TAC) surgery. After surgery, the mice were fed on either normal diet or HFD for 8 or 16 weeks. KEY FINDINGS: HFD feeding exerted opposite effects on cardiac function at different time points post-surgery. Short-term HFD feeding (8 wk) protected the heart against pressure overload, inhibiting cardiac hypertrophy and improving cardiac function, while long-term HFD feeding (16 wk) aggravated cardiac dysfunction in TAC mice. Short-term HFD feeding elevated cardiac fatty acid utilization, while long-term HFD feeding showed no significant effects on cardiac fatty acid utilization in TAC mice. Specifically, an increase in cardiac fatty acid utilization was accompanied with activated mitophagy and improved mitochondrial function. Palmitic acid treatment (400 µM, 2 h) stimulated fatty acid oxidation and mitophagy in neonatal myocytes. Mechanistically, fatty acid utilization stimulated mitophagy through upregulation of Parkin. Cardiac-specific knockdown of Parkin abolished the protective effects of short-term HFD feeding on cardiac function in TAC mice. SIGNIFICANCES: These results suggested that short-term but not long-term HFD feeding protects against pressure overload-induced heart failure through activation of mitophagy, and dietary fat intake should be used with caution in treatment of heart failure.


Asunto(s)
Insuficiencia Cardíaca/metabolismo , Insuficiencia Cardíaca/prevención & control , Mitofagia/fisiología , Animales , Presión Sanguínea/fisiología , Cardiomegalia/metabolismo , China , Dieta Alta en Grasa/métodos , Modelos Animales de Enfermedad , Metabolismo Energético , Ácidos Grasos/metabolismo , Insuficiencia Cardíaca/fisiopatología , Masculino , Ratones , Ratones Endogámicos C57BL , Miocardio/metabolismo , Miocitos Cardíacos/metabolismo , Oxidación-Reducción
9.
Biomed Res Int ; 2021: 9491615, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33521132

RESUMEN

Background: L-carnitine mediates the utilization of fatty acids and glucose in the myocardium. The potential of L-carnitine in managing dilated cardiomyopathy (DCM) in patients has been extensively reported, with additional benefits. Objective: This meta-analysis purposed to explore the clinical efficacy of L-carnitine therapy on DCM patients. Methods: We searched publications up to May 2020 from several databases including PubMed, Embase, Cochrane Library, Chinese Biomedical (CBM) database, Chinese Science and Technology Periodicals database (VIP), Chinese National Knowledge Infrastructure (CNKI) database, and Wanfang database. Subsequently, publications that met the inclusion criteria were systematically evaluated by two independent reviewers. Results: A total of 23 RCTs conducted in China with 1455 DCM patients were included in this study. In the meta-analysis, L-carnitine therapy was associated with a considerable improvement in the overall efficacy (RR = 1.28, 95% CI (1.21-1.36), P < 0.0001), left ventricular ejection fraction (LVEF) (MD = 6.16%, 95% CI (4.50, 7.83), P < 0.0001), and cardiac output (CO) (MD = 0.88 L/min, 95% CI (0.51, 1.25), P < 0.0001) as compared to the control group. Moreover, L-carnitine therapy significantly decreased left ventricular end-diastolic dimension (LVEDD) (MD = -2.53, 95% CI (-3.95, -1.12), P = 0.0005), brain natriuretic peptide (BNP) (SMD = -1.71 ng/L, 95% CI (-3.02, -0.40), P = 0.01), and the transforming growth factor-beta (TGF-ß1) (MD = -56.78 ng/L, 95% CI (-66.02, -47.53), P < 0.0001). Conclusions: L-carnitine potentially enhanced the therapeutic efficiency in DCM patients. Following weaknesses in the evidence due to low methodological quality and high clinical heterogeneity in the included studies, well-designed trials are recommended.


Asunto(s)
Cardiomiopatía Dilatada/tratamiento farmacológico , Carnitina/uso terapéutico , Ácidos Grasos/metabolismo , Glucosa/metabolismo , Miocardio/metabolismo , Humanos , Péptido Natriurético Encefálico/metabolismo , Ensayos Clínicos Controlados Aleatorios como Asunto , Proyectos de Investigación , Riesgo , Volumen Sistólico , Factor de Crecimiento Transformador beta1/metabolismo , Función Ventricular Izquierda
10.
Nat Commun ; 12(1): 1252, 2021 02 23.
Artículo en Inglés | MEDLINE | ID: mdl-33623047

RESUMEN

Upon starvation, cells rewire their metabolism, switching from glucose-based metabolism to mitochondrial oxidation of fatty acids, which require the transfer of FAs from lipid droplets (LDs) to mitochondria at mitochondria-LD membrane contact sites (MCSs). However, factors responsible for FA transfer at these MCSs remain uncharacterized. Here, we demonstrate that vacuolar protein sorting-associated protein 13D (VPS13D), loss-of-function mutations of which cause spastic ataxia, coordinates FA trafficking in conjunction with the endosomal sorting complex required for transport (ESCRT) protein tumor susceptibility 101 (TSG101). The VPS13 adaptor-binding domain of VPS13D and TSG101 directly remodels LD membranes in a cooperative manner. The lipid transfer domain of human VPS13D binds glycerophospholipids and FAs in vitro. Depletion of VPS13D, TSG101, or ESCRT-III proteins inhibits FA trafficking from LDs to mitochondria. Our findings suggest that VPS13D mediates the ESCRT-dependent remodeling of LD membranes to facilitate FA transfer at mitochondria-LD contacts.


Asunto(s)
Proteínas de Unión al ADN/metabolismo , Complejos de Clasificación Endosomal Requeridos para el Transporte/metabolismo , Ácidos Grasos/metabolismo , Gotas Lipídicas/metabolismo , Mitocondrias/metabolismo , Proteínas/metabolismo , Factores de Transcripción/metabolismo , Secuencias de Aminoácidos , Secuencia de Aminoácidos , Animales , Células COS , Chlorocebus aethiops , Fluorescencia , Células HEK293 , Humanos , Modelos Biológicos , Proteínas Mutantes/metabolismo , Dominios Proteicos , Estructura Secundaria de Proteína , Proteínas/química
11.
Nat Metab ; 3(2): 228-243, 2021 02.
Artículo en Inglés | MEDLINE | ID: mdl-33619380

RESUMEN

Obesity is a major risk factor for cardiometabolic diseases. Nevertheless, a substantial proportion of individuals with obesity do not suffer cardiometabolic comorbidities. The mechanisms that uncouple adiposity from its cardiometabolic complications are not fully understood. Here, we identify 62 loci of which the same allele is significantly associated with both higher adiposity and lower cardiometabolic risk. Functional analyses show that the 62 loci are enriched for genes expressed in adipose tissue, and for regulatory variants that influence nearby genes that affect adipocyte differentiation. Genes prioritized in each locus support a key role of fat distribution (FAM13A, IRS1 and PPARG) and adipocyte function (ALDH2, CCDC92, DNAH10, ESR1, FAM13A, MTOR, PIK3R1 and VEGFB). Several additional mechanisms are involved as well, such as insulin-glucose signalling (ADCY5, ARAP1, CREBBP, FAM13A, MTOR, PEPD, RAC1 and SH2B3), energy expenditure and fatty acid oxidation (IGF2BP2), browning of white adipose tissue (CSK, VEGFA, VEGFB and SLC22A3) and inflammation (SH2B3, DAGLB and ADCY9). Some of these genes may represent therapeutic targets to reduce cardiometabolic risk linked to excess adiposity.


Asunto(s)
Adiposidad/genética , Sitios Genéticos/genética , Estudio de Asociación del Genoma Completo , Obesidad/genética , Adipocitos/metabolismo , Adipocitos Marrones/fisiología , Adipocitos Blancos/fisiología , Tejido Adiposo/metabolismo , Alelos , Metabolismo Energético/fisiología , Ácidos Grasos/metabolismo , Glucosa/metabolismo , Humanos , Insulina/metabolismo , Familia de Multigenes/genética , Obesidad/complicaciones , Medición de Riesgo , Transducción de Señal/fisiología
12.
Trop Anim Health Prod ; 53(1): 63, 2021 Jan 03.
Artículo en Inglés | MEDLINE | ID: mdl-33389265

RESUMEN

This study was carried out to determine the effects of addition of humate, probiotic, and their combination into diets on performance, egg quality, and yolk fatty acid composition of hens during the second laying period. Lohmann LSL white layers (n = 192), 46 weeks of age, were randomly divided into 4 groups and fed with basal diet (control, C), 0.3% humate (H), 0.3% probiotic (P), 0.15% humate + 0.15% probiotic (HP) for 18 weeks. Feed consumption and egg production were determined daily, egg weight was measured biweekly, and body weights were recorded at the beginning and the end of the experiment. Also, 12 egg samples from each group were randomly collected to determine the egg quality every 30 days. Laying performance, yolk color, and fatty acid composition were significantly (P < 0.05 and P < 0.01) affected by addition of humate, probiotic, and their combination into diets of layers. The HP group had higher cracked egg yield and feed conversion ratio values than control and H and P groups. Except for egg yolk color, the other egg quality parameters such as shape index, shell strength, shell thickness, albumen index, yolk index, and Haught unit were not affected by treatment (P < 0.05 and P < 0.01). The egg yolks of treatment groups had less stearic acid than those of control group. In conclusion, supplementation of humate and probiotic into the diets of laying hens increased monounsaturated fatty acids in yolk and improved feed conversion ratio and egg yolk color.


Asunto(s)
Pollos , Yema de Huevo/efectos de los fármacos , Ácidos Grasos/metabolismo , Sustancias Húmicas , Probióticos/farmacología , Animales , Dieta/veterinaria , Suplementos Dietéticos , Yema de Huevo/metabolismo , Femenino , Óvulo
13.
Angew Chem Int Ed Engl ; 60(13): 7098-7110, 2021 03 22.
Artículo en Inglés | MEDLINE | ID: mdl-33469977

RESUMEN

We investigate binding of linoleate and other potential ligands to the recently discovered fatty acid binding site in the SARS-CoV-2 spike protein, using docking and molecular dynamics simulations. Simulations suggest that linoleate and dexamethasone stabilize the locked spike conformation, thus reducing the opportunity for ACE2 interaction. In contrast, cholesterol may expose the receptor-binding domain by destabilizing the closed structure, preferentially binding to a different site in the hinge region of the open structure. We docked a library of FDA-approved drugs to the fatty acid site using an approach that reproduces the structure of the linoleate complex. Docking identifies steroids (including dexamethasone and vitamin D); retinoids (some known to be active in vitro, and vitamin A); and vitamin K as potential ligands that may stabilize the closed conformation. The SARS-CoV-2 spike fatty acid site may bind a diverse array of ligands, including dietary components, and therefore provides a promising target for therapeutics or prophylaxis.


Asunto(s)
Simulación de Dinámica Molecular , Retinoides/metabolismo , Glicoproteína de la Espiga del Coronavirus/metabolismo , Esteroides/metabolismo , Vitaminas/metabolismo , Sitios de Unión , /virología , Ácidos Grasos/química , Ácidos Grasos/metabolismo , Humanos , Ligandos , Simulación del Acoplamiento Molecular , Estructura Cuaternaria de Proteína , Retinoides/química , /metabolismo , Glicoproteína de la Espiga del Coronavirus/química , Esteroides/química , Vitaminas/química
14.
Life Sci ; 268: 119000, 2021 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-33417961

RESUMEN

AIM: This study aimed to reveal the effects of icaritin (ICT) on lipotoxicity induced by palmitate (PA) in hepatic cells and steatosis in high-fat diet (HFD)-fed mice as well as exploring the potential mechanisms. MAIN METHODS: Primary mouse hepatocytes and human hepatoma Huh7 cells were used to evaluate ICT effect in vitro. HFD-fed mice were used to evaluate the ICT effect in vivo. RESULTS: In vitro study indicated that ICT significantly rescued PA-induced steatosis, mainly through a combination of robust increased mitochondrial respiration, fatty acid oxidation and mildly decreased synthesis of fatty acid. An HFD-fed mouse model with 8 weeks HFD-fed showed metabolic disorders, while ICT application significantly reduced the weight, serum glucose levels, insulin resistance, hepatic steatosis level and adipose contents. In consistent with the observations in cell lines, ICT rescued the HFD-impaired functions and contents of key factors related to fatty acid ß-oxidation through elevated expression of peroxisome proliferator-activated receptor α (PPARα). Meanwhile, it also reversed the decreased phosphoryl levels of AKT and glucogen synthase kinase 3 (GSK3ß), leading to the improvement of insulin resistance. SIGNIFICANCE: ICT administration had a therapeutic effect on PA- or HFD-induced hepatic steatosis and metabolic disorders. It may provide a novel strategy to construct preventive and therapeutic means for hepatic steatosis.


Asunto(s)
Ácidos Grasos/metabolismo , Flavonoides/farmacología , Hepatocitos/efectos de los fármacos , Resistencia a la Insulina , Enfermedad del Hígado Graso no Alcohólico/tratamiento farmacológico , Adenosina Trifosfato/metabolismo , Animales , Dieta Alta en Grasa/efectos adversos , Glucógeno Sintasa Quinasa 3 beta/genética , Glucógeno Sintasa Quinasa 3 beta/metabolismo , Hepatocitos/metabolismo , Hepatocitos/patología , Humanos , Masculino , Ratones Endogámicos C57BL , Enfermedad del Hígado Graso no Alcohólico/etiología , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Sobrepeso/tratamiento farmacológico , Sobrepeso/etiología , Sobrepeso/fisiopatología , Oxidación-Reducción , Palmitatos/toxicidad , Proteínas Proto-Oncogénicas c-akt/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Triglicéridos/metabolismo
15.
Methods Mol Biol ; 2251: 39-53, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33481230

RESUMEN

Our knowledge of the role and biology of the different phosphoinositides has greatly expanded over recent years. Reversible phosphorylation by specific kinases and phosphatases of positions 3, 4, and 5 on the inositol ring is a highly dynamic process playing a critical role in the regulation of the spatiotemporal recruitment and binding of effector proteins. The specific phosphoinositide kinases and phosphatases are key players in the control of many cellular functions, including proliferation, survival, intracellular trafficking, or cytoskeleton reorganization. Several of these enzymes are mutated in human diseases. The impact of the fatty acid composition of phosphoinositides in their function is much less understood. There is an important molecular diversity in the fatty acid side chains of PI. While stearic and arachidonic fatty acids are the major acyl species in PIP, PIP2, and PIP3, other fatty acid combinations are also found. The role of these different molecular species is still unknown, but it is important to quantify these different molecules and their potential changes during cell stimulation to better characterize this emerging field. Here, we describe a sensitive high-performance liquid chromatography-mass spectrometry method that we used for the first time to profile the changes in phosphoinositide molecular species (summed fatty acyl chain profiles) in human and mouse platelets under resting conditions and following stimulation. This method can be applied to other hematopoietic primary cells isolated from human or experimental animal models.


Asunto(s)
Plaquetas/metabolismo , Fosfatidilinositoles/análisis , Espectrometría de Masas en Tándem/métodos , 1-Fosfatidilinositol 4-Quinasa/metabolismo , Animales , Fenómenos Bioquímicos , Línea Celular , Células Cultivadas , Cromatografía Liquida/métodos , Ácidos Grasos/metabolismo , Inositol/química , Ratones , Fosfatidilinositol 3-Quinasas/análisis , Fosfatidilinositol 3-Quinasas/química , Fosfatidilinositol 3-Quinasas/metabolismo , Fosfatos de Fosfatidilinositol/análisis , Fosfatos de Fosfatidilinositol/química , Fosfatos de Fosfatidilinositol/metabolismo , Fosfatidilinositoles/química , Fosfatidilinositoles/metabolismo , Monoéster Fosfórico Hidrolasas/metabolismo , Transducción de Señal/fisiología
16.
Food Chem ; 346: 128897, 2021 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-33406455

RESUMEN

Pichia fermentans Z9Y-3 and its intracellular enzymes were inoculated along with S. cerevisiae in synthetic grape must to modulate fruity ester production. The levels of ester-related enzymes, ester precursors, and fruity esters were monitored every 24 h during fermentation. Results showed that the levels of ethyl acetate, acetate higher alcohol esters (AHEs), short chain fatty acid ethyl esters (SFEs), and medium chain fatty acid ethyl esters (MFEs) were significantly enhanced in mixed fermentation. Pearson correlation analysis further revealed that higher alcohols and fatty acids played a more important role in fruity ester production than enzymes; Particularly, the correlation coefficient between fatty acids and MFEs was 0.940. In addition, supplementation of medium chain fatty acids (7.2 mg/L) at the metaphase of single S. cerevisiae fermentation improved ethyl acetate, AHE, SFE, and MFE production by 42.56%, 21.00%, 61.33%, and 90.04%, respectively, although the high level of ethyl acetate might result in off-flavors.


Asunto(s)
Ésteres/química , Ésteres/metabolismo , Ácidos Grasos/metabolismo , Fermentación , Frutas/química , Pichia/metabolismo , Saccharomyces cerevisiae/metabolismo , Gusto , Vitis/química , Vitis/microbiología , Vino/análisis
17.
Ecotoxicol Environ Saf ; 210: 111852, 2021 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-33418155

RESUMEN

Symbiosis of marine algae is inevitable in the marine environment, and species may occur interaction on the growth. In this study, the macroalgae Ulva pertusa and marine microalgae Heterosigma akashiwo were selected as target species to study the interaction mechanism between them. After the 8 days of co-cultivation, the inhibition on growth was observed for both of U. pertusa and H. akashiwo. Eight fatty acids in U. pertusa was detected, with the significant decrease in contents of polyunsaturated fatty acids (PUFAs) especially for C18:2, C18:3n-3 and C18:3n-6. Twelve fatty acids in H. akashiwo was detected, with the significant change for PUFAs. PUFA concentrations in the co-culture group were less than those in the mono-culture. Meanwhile the principal component analysis was conducted to insight into the interaction between U. pertusa and H. akashiwo by fatty acids content and carbon stable isotope ratio of fatty acids (δ13CFAs). Fatty acid content could not distinguish mono and co-culture. However, δ13CFAs could distinguish not only the culture time of algae, but also the living environment of algae. In addition, this study combined fatty acids content and δ13CFAs to explore the release of fatty acids by algae into the seawater. The C18:3n-3 was identified as the allelochemical released by U. pertusa to inhibit the growth of H. akashiwo. The ratio of δ13CFAs in seawater decreased. This study provides a theoretical basis for the symbiosis of marine algae, and a new method of compound-specific stable carbon isotopes was used to better explore the metabolism of fatty acids in algae.


Asunto(s)
Ácidos Grasos/metabolismo , Microalgas/metabolismo , Estramenopilos/metabolismo , Ulva/metabolismo , Isótopos de Carbono/análisis , Isótopos de Carbono/metabolismo , Ácidos Grasos/análisis , Agua de Mar/química , Estramenopilos/crecimiento & desarrollo , Simbiosis , Ulva/crecimiento & desarrollo
18.
Viruses ; 13(1)2021 Jan 11.
Artículo en Inglés | MEDLINE | ID: mdl-33440724

RESUMEN

Enteric symptomology seen in early-stage severe acute respiratory syndrome (SARS)-2003 and COVID-19 is evidence of virus replication occurring in the intestine, liver and pancreas. Aberrant lipid metabolism in morbidly obese individuals adversely affects the COVID-19 immune response and increases disease severity. Such observations are in line with the importance of lipid metabolism in COVID-19, and point to the gut as a site for intervention as well as a therapeutic target in treating the disease. Formation of complex lipid membranes and palmitoylation of coronavirus proteins are essential during viral replication and assembly. Inhibition of fatty acid synthase (FASN) and restoration of lipid catabolism by activation of AMP-activated protein kinase (AMPK) impede replication of coronaviruses closely related to SARS-coronavirus-2 (CoV-2). In vitro findings and clinical data reveal that the FASN inhibitor, orlistat, and the AMPK activator, metformin, may inhibit coronavirus replication and reduce systemic inflammation to restore immune homeostasis. Such observations, along with the known mechanisms of action for these types of drugs, suggest that targeting fatty acid lipid metabolism could directly inhibit virus replication while positively impacting the patient's response to COVID-19.


Asunto(s)
/metabolismo , Ácidos Grasos/metabolismo , Metabolismo de los Lípidos , /fisiología , Proteínas Quinasas Activadas por AMP/metabolismo , Proteínas Quinasas Activadas por AMP/farmacología , Antivirales/farmacología , Antivirales/uso terapéutico , /virología , Sistema Digestivo/efectos de los fármacos , Sistema Digestivo/virología , Ácido Graso Sintasas/antagonistas & inhibidores , Ácido Graso Sintasas/metabolismo , Humanos , Metformina/uso terapéutico , Obesidad/tratamiento farmacológico , Obesidad/metabolismo , Obesidad/virología , Orlistat/uso terapéutico , Proteínas Virales/metabolismo , Ensamble de Virus/efectos de los fármacos , Replicación Viral/efectos de los fármacos
19.
Nat Rev Cancer ; 21(3): 162-180, 2021 03.
Artículo en Inglés | MEDLINE | ID: mdl-33462499

RESUMEN

Metastasis formation is the major cause of death in most patients with cancer. Despite extensive research, targeting metastatic seeding and colonization is still an unresolved challenge. Only recently, attention has been drawn to the fact that metastasizing cancer cells selectively and dynamically adapt their metabolism at every step during the metastatic cascade. Moreover, many metastases display different metabolic traits compared with the tumours from which they originate, enabling survival and growth in the new environment. Consequently, the stage-dependent metabolic traits may provide therapeutic windows for preventing or reducing metastasis, and targeting the new metabolic traits arising in established metastases may allow their eradication.


Asunto(s)
Metástasis de la Neoplasia , Neoplasias/metabolismo , Acetatos/metabolismo , Adenosina Trifosfato/biosíntesis , Animales , Plasticidad de la Célula , Ácidos Grasos/metabolismo , Glutamina/metabolismo , Humanos , Ácido Láctico/metabolismo , Neoplasias/patología , Células Neoplásicas Circulantes/metabolismo , Ácido Pirúvico/metabolismo
20.
Arterioscler Thromb Vasc Biol ; 41(3): 1062-1075, 2021 03.
Artículo en Inglés | MEDLINE | ID: mdl-33472399

RESUMEN

OBJECTIVE: Plaque necrosis is a key feature of defective resolution in atherosclerosis. Recent evidence suggests that necroptosis promotes plaque necrosis; therefore, we sought to determine how necroptotic cells (NCs) impact resolution programs in plaques. Approach and Results: To investigate the role(s) of necroptosis in advanced atherosclerosis, we used mice deficient of Mlkl, an effector of necroptosis. Mlkl-/- mice that were injected with a gain-of-function mutant PCSK9 (AAV8-gof-PCSK9) and fed a Western diet for 16 weeks, showed significantly less plaque necrosis, increased fibrous caps and improved efferocytosis compared with AAV8-gof-PCSK9 injected wt controls. Additionally, hypercholesterolemic Mlkl-/- mice had a significant increase in proresolving mediators including resolvin D1 (RvD1) and a decrease in prostanoids including thromboxane in plaques and in vitro. We found that exuberant thromboxane released by NCs impaired the clearance of both apoptotic cells and NCs through disruption of oxidative phosphorylation in macrophages. Moreover, we found that NCs did not readily synthesize RvD1 and that exogenous administration of RvD1 to macrophages rescued NC-induced defective efferocytosis. RvD1 also enhanced the uptake of NCs via the activation of p-AMPK (AMP-activated protein kinase), increased fatty acid oxidation, and enhanced oxidative phosphorylation in macrophages. CONCLUSIONS: These results suggest that NCs derange resolution by limiting key SPMs and impairing the efferocytic repertoire of macrophages. Moreover, these findings provide a molecular mechanism for RvD1 in directing proresolving metabolic programs in macrophages and further suggests RvD1 as a potential therapeutic strategy to limit NCs in tissues. Graphic Abstract: A graphic abstract is available for this article.


Asunto(s)
Ácidos Docosahexaenoicos/metabolismo , Ácidos Grasos/metabolismo , Macrófagos/metabolismo , Necroptosis/fisiología , Ácido 15-Hidroxi-11 alfa,9 alfa-(epoximetano)prosta-5,13-dienoico/farmacología , Proteínas Quinasas Activadas por AMP/metabolismo , Animales , Apoptosis , Femenino , Macrófagos/efectos de los fármacos , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Necrosis , Fosforilación Oxidativa , Fagocitosis , Placa Aterosclerótica/metabolismo , Placa Aterosclerótica/patología , Prostaglandinas/metabolismo , Proteínas Quinasas/deficiencia , Proteínas Quinasas/genética
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