fatty acid cycling Dotaz Zobrazit nápovědu
Cílem naší studie bylo stanovit u asymptomatických prvostupňových příbuzných pacientů s kardiovaskulárním onemocněním korelaci mezi hladinou adipocyte fatty acid binding proteinu (A-FABP) jako možným spojovacím článkem mezi metabolickým syndromem a aterosklerózou, velikostí kalciového skóre (KS) a laboratorními parametry včetně indexů inzulinové rezistence. Soubor a metodika: Bylo vyšetřeno 82 osob (53 mužů) průměrného věku 52,79 ? 9,6 roku, u kterých byla provedena antropometrická a fyzikální vyšetření (stanovení tělesné hmotnosti, výšky, výpočet body mass indexu – BMI, měření kazuálního krevního tlaku) a laboratorní vyšetření (kyselina močová, kreatinin, lipidové spektrum, inzulin, glukóza, C-reaktivní protein, fibrinogen, glykovaný hemoglobin, adipocyte fatty acid binding protein – A-FABP) a stanovení indexů inzulinové rezistence HOMA a QUICKI. Celkové kalciové skóre (KS) bylo stanoveno Agatstonovou metodou, bez nutnosti podávat kontrastní látku. Výsledky: Hladina A-FABP nezávisí statisticky významně na kategorizovaném KS ani na nekategorizovaných hodnotách KS (p = 0,22). Existuje statisticky významná pozitivní závislost hladiny A-FABP na indexu HOMA (p = 0,00688) a statisticky významná negativní závislost na indexu QUICKI (p = 0,0068). Hladina A-FABP je statisticky významně vyšší u žen (p = 0,048), u starších osob (p = 0,043) a u osob s vyšší kategorií BMI (p = 0,029). Ze spojitých proměnných se statisticky významně liší hladina A-FABP vzhledem k věku (p = 0,002), kreatininu (p = 0,026), inzulinu (p = 0,005) a BMI (p = 0,031). Závěr: V naší studii jsme potvrdili u skupiny asymptomatických prvostupňových příbuzných pacientů s KVO korelaci hladiny A-FABP s indexy inzulinové rezistence, BMI, věkem, pohlavím a hodnotou inzulinu a kreatininu. A-FABP se zdá být slibným markerem při stanovení rizika KVO, nicméně tato skutečnost vyžaduje další klinické studie.
The objective of our study was to determine a correlation between the level of adipocyte fatty acid-binding protein (A-FABP) (as a possible link between metabolic syndrome and atherosclerosis), the calcium score (CS) and laboratory parameters, including insulin resistance indices in asymptomatic first degree relatives of patients with cardiovascular diseases. Set and methodology: Examination was conducted in 82 persons (53 male) with the average age of 52.79 ? 9.6. The examinations consisted of anthropometric and physical tests (determination of body weight, height, body mass index – BMI and casual blood pressure measurement), laboratory analysis (uric acid, creatinine, lipid panel, insulin, glucose, C-reactive protein, fibrinogen, glycated hemoglobin, adipocyte fatty acid-binding protein – A-FABP) and determination of insulin resistance indices HOMA and QUICKI. Total calcium score (CS) was determined by the Agatston method without the need to administer a contrast agent. Results: The value of the A-FABP level does not show a statistically significant dependence on the categorised CS or on non-categorised CS values. There is a statistically significant positive dependence of the level of A-FABP on the HOMA index (p = 0.00688) and a statistically significant negative dependence on the QUICKI index (p = 0.0068). The A-FABP level is statistically significantly higher in women (p = 0.048), in elder persons (p = 0.043), and in persons with higher BMI values (p = 0.029). Among continuous variables, statistically significant is the difference in the A-FABP level in relation to age (p = 0.002), creatinine (p = 0.026), insulin (p = 0.005), and BMI (p = 0.031). Conclusion: Our study confirmed the correlation of the A-FABP level with insulin resistance indices, BMI, age, gender, and insulin and creatinine levels in a group of asymptomatic first degree relatives of patients with cardiovascular diseases. A-FABP could potentially be a marker when determining the risk of CVD; however, this conclusion requires additional clinical trials.
- Klíčová slova
- kardiovaskulární onemocnění,
- MeSH
- dospělí MeSH
- hodnocení rizik MeSH
- index tělesné hmotnosti MeSH
- inzulin krev MeSH
- inzulinová rezistence MeSH
- kalcinóza * diagnóza radiografie MeSH
- kardiovaskulární nemoci * prevence a kontrola MeSH
- klinické laboratorní techniky MeSH
- kreatin krev MeSH
- lidé MeSH
- proteiny vázající mastné kyseliny * krev MeSH
- průřezové studie MeSH
- reprodukovatelnost výsledků MeSH
- rizikové faktory MeSH
- rodina MeSH
- sérum chemie MeSH
- sexuální faktory MeSH
- statistika jako téma MeSH
- tělesné váhy a míry MeSH
- věkové faktory MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
Long-chain n-3 polyunsaturated fatty acids (Omega-3) and anti-diabetic drugs thiazolidinediones (TZDs) exhibit additive effects in counteraction of dietary obesity and associated metabolic dysfunctions in mice. The underlying mechanisms need to be clarified. Here, we aimed to learn whether the futile cycle based on the hydrolysis of triacylglycerol and re-esterification of fatty acids (TAG/FA cycling) in white adipose tissue (WAT) could be involved. We compared Omega-3 (30 mg/g diet) and two different TZDs-pioglitazone (50 mg/g diet) and a second-generation TZD, MSDC-0602K (330 mg/g diet)-regarding their effects in C57BL/6N mice fed an obesogenic high-fat (HF) diet for 8 weeks. The diet was supplemented or not by the tested compound alone or with the two TZDs combined individually with Omega-3. Activity of TAG/FA cycle in WAT was suppressed by the obesogenic HF diet. Additive effects in partial rescue of TAG/FA cycling in WAT were observed with both combined interventions, with a stronger effect of Omega-3 and MSDC-0602K. Our results (i) supported the role of TAG/FA cycling in WAT in the beneficial additive effects of Omega-3 and TZDs on metabolism of diet-induced obese mice, and (ii) showed differential modulation of WAT gene expression and metabolism by the two TZDs, depending also on Omega-3.
- MeSH
- bílá tuková tkáň metabolismus MeSH
- dieta s vysokým obsahem tuků MeSH
- hypoglykemika farmakologie MeSH
- kyseliny mastné omega-3 aplikace a dávkování farmakologie MeSH
- lipogeneze účinky léků MeSH
- mastné kyseliny metabolismus MeSH
- metabolismus lipidů účinky léků MeSH
- myši inbrední C57BL MeSH
- myši obézní MeSH
- myši MeSH
- obezita farmakoterapie metabolismus MeSH
- pioglitazon farmakologie MeSH
- thiazolidindiony aplikace a dávkování farmakologie MeSH
- triglyceridy metabolismus MeSH
- tukové buňky účinky léků MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Adenine nucleotide translocase (ANT) is a well-known mitochondrial exchanger of ATP against ADP. In contrast, few studies have shown that ANT also mediates proton transport across the inner mitochondrial membrane. The results of these studies are controversial and lead to different hypotheses about molecular transport mechanisms. We hypothesized that the H+-transport mediated by ANT and uncoupling proteins (UCP) has a similar regulation pattern and can be explained by the fatty acid cycling concept. The reconstitution of purified recombinant ANT1 in the planar lipid bilayers allowed us to measure the membrane current after the direct application of transmembrane potential ΔΨ, which would correspond to the mitochondrial states III and IV. Experimental results reveal that ANT1 does not contribute to a basal proton leak. Instead, it mediates H+ transport only in the presence of long-chain fatty acids (FA), as already known for UCPs. It depends on FA chain length and saturation, implying that FA's transport is confined to the lipid-protein interface. Purine nucleotides with the preference for ATP and ADP inhibited H+ transport. Specific inhibitors of ATP/ADP transport, carboxyatractyloside or bongkrekic acid, also decreased proton transport. The H+ turnover number was calculated based on ANT1 concentration determined by fluorescence correlation spectroscopy and is equal to 14.6 ± 2.5 s-1. Molecular dynamic simulations revealed a large positively charged area at the protein/lipid interface that might facilitate FA anion's transport across the membrane. ANT's dual function-ADP/ATP and H+ transport in the presence of FA-may be important for the regulation of mitochondrial membrane potential and thus for potential-dependent processes in mitochondria. Moreover, the expansion of proton-transport modulating drug targets to ANT1 may improve the therapy of obesity, cancer, steatosis, cardiovascular and neurodegenerative diseases.
- MeSH
- iontový transport MeSH
- konformace proteinů MeSH
- mastné kyseliny metabolismus MeSH
- membránový potenciál mitochondrií MeSH
- mitochondrie metabolismus MeSH
- myši MeSH
- protony * MeSH
- translokátor adeninových nukleotidů 1 chemie metabolismus MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- MeSH
- Escherichia coli metabolismus MeSH
- finanční podpora výzkumu jako téma MeSH
- lidé MeSH
- mastné kyseliny chemie metabolismus MeSH
- membránové transportní proteiny fyziologie metabolismus MeSH
- mitochondriální proteiny fyziologie MeSH
- mitochondrie fyziologie MeSH
- transport proteinů MeSH
- Check Tag
- lidé MeSH
Obstructive sleep apnea syndrome, characterized by repetitive episodes of tissue hypoxia, is associated with several metabolic impairments. Role of fatty acids and lipids attracts attention in its pathogenesis for their metabolic effects. Parallelly, hypoxia-induced activation of reverse tricarboxylic acid cycle (rTCA) with reductive glutamine metabolism provides precursor molecules for de novo lipogenesis. Gas-permeable cultureware was used to culture L6-myotubes in chronic hypoxia (12%, 4% and 1% O2) with 13C labelled glutamine and inhibitors of glutamine uptake or rTCA-mediated lipogenesis. We investigated changes in lipidomic profile, 13C appearance in rTCA-related metabolites, gene and protein expression of rTCA-related proteins and glutamine transporters, glucose uptake and lactate production. Lipid content increased by 308% at 1% O2, predominantly composed of saturated fatty acids, while triacylglyceroles containing unsaturated fatty acids and membrane lipids (phosphatidylcholines, phosphatidylethanolamines, phosphatidylinositol) decreased by 20-70%. rTCA labelling of malate, citrate and 2-hydroxyglutarate increased by 4.7-fold, 2.2-fold and 1.9-fold in 1% O2, respectively. ATP-dependent citrate lyase inhibition in 1% O2 decreased lipid amount by 23% and increased intensity of triacylglyceroles containing unsaturated fatty acids by 56-80%. Lactate production increased with hypoxia. Glucose uptake dropped by 75% with progression of hypoxia from 4% to 1% O2. Protein expression remained unchanged. Altogether, hypoxia modified cell metabolism leading to lipid composition alteration and rTCA activation.
Fatty acids are essential components of biological membranes, important for the maintenance of cellular structures, especially in organisms with complex life cycles like protozoan parasites. Apicomplexans are obligate parasites responsible for various deadly diseases of humans and livestock. We analyzed the fatty acids produced by the closest phototrophic relatives of parasitic apicomplexans, the chromerids Chromera velia and Vitrella brassicaformis, and investigated the genes coding for enzymes involved in fatty acids biosynthesis in chromerids, in comparison to their parasitic relatives. Based on evidence from genomic and metabolomic data, we propose a model of fatty acid synthesis in chromerids: the plastid-localized FAS-II pathway is responsible for the de novo synthesis of fatty acids reaching the maximum length of 18 carbon units. Short saturated fatty acids (C14:0-C18:0) originate from the plastid are then elongated and desaturated in the cytosol and the endoplasmic reticulum. We identified giant FAS I-like multi-modular enzymes in both chromerids, which seem to be involved in polyketide synthesis and fatty acid elongation. This full-scale description of the biosynthesis of fatty acids and their derivatives provides important insights into the reductive evolutionary transition of a phototropic algal ancestor to obligate parasites.
- MeSH
- Apicomplexa klasifikace genetika metabolismus MeSH
- biosyntetické dráhy genetika MeSH
- desaturasy mastných kyselin klasifikace genetika metabolismus MeSH
- druhová specificita MeSH
- elongasy mastných kyselin klasifikace genetika metabolismus MeSH
- fylogeneze MeSH
- lidé MeSH
- mastné kyseliny biosyntéza MeSH
- molekulární evoluce MeSH
- protozoální infekce parazitologie MeSH
- protozoální proteiny klasifikace genetika metabolismus MeSH
- synthasa mastných kyselin, typ 2 klasifikace genetika metabolismus MeSH
- synthasa mastných kyselin, typ I klasifikace genetika metabolismus MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
