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Il ruolo degli endocannabinoidi nell'invecchiamento e nelle patologie dismetaboliche ad esso correlate
No full textFluidità di membrana, omega 3 ed obesità
No full textNumerosi studi hanno dimostrato una correlazione tra obesità e fluidità di membrana [1, 2]. Alcune recenti ricerche da noi condotte hanno messo in evidenza che gli eritrociti di donne obese rispetto a quelli dei controlli normopeso presentavano una significativa riduzione dei livelli dei principali antiossidanti, della fluidità e del rapporto tra gli acidi grassi omega-3 e omega-6 delle loro membrane, e che le tali alterazioni strutturali e funzionali erano significativamente più marcate nelle obese con sindrome metabolica [3]. La letteratura scientifica ha dimostrato che la fluidità e la composizione fosfolipidica delle membrane eritrocitarie correla significativamente con quella delle cellule neuronali e di molti altri tessuti, e che l’alterata fluidità delle membrane neuronali concorre a ridurre l’efficienza dei recettori per i mediatori del controllo della sazietà e della termogenesi dell’asse “gut-brain” (anandamide, 2-o-arachidonoil-glicerolo, neuropetide Y, Agouti-related peptide, etc.). Da tutto ciò si evince che queste alterazioni strutturali e funzionali delle membrane degli obesi possono contribuire a peggiorare ulteriormente il controllo del peso corporeo ed il rischio di insorgenza della sindrome metabolica. Inoltre, la perdita di fluidità delle membrane e la riduzione dei livelli dei principali antiossidanti diminuisce a livello mitocondriale l’efficienza degli enzimi della catena respiratoria nel produrre ATP. Di conseguenza si riduce l’attività delle ATP-asi per lo ione Ca e ciò comporta un aumento della sua concentrazione intracellulare. L’aumento del Ca attiva la fosfolipasi A2 e promuove il rilascio dai fosfolipidi degli acidi grassi polinsaturi della serie omega-6 (ac. Arachidonico) e della serie omega-3 (ac. Docosaesanoico, DHA). Numerose sono le correlazioni tra queste alterazioni metaboliche e l’obesità. In particolare, le evidenze della letteratura dimostrano che:
• A livello cerebrale, il calo del DHA legato ai fosfolipidi (DHA-PL) concorre a promuovere: a) un ulteriore irrigidimento delle membrane e di conseguenza un aumento della resistenza all’insulina; b) l’attivazione delle lipo- e delle ciclo-ossigenasi e di conseguenza un aumento dell’infiammazione e della vasocostrizione tissutale; c) il rilascio (DHA-PL- indotto) di diversi mediatori che concorrono ad aumentare la sensazione di fame ed a regolare la termogenesi.
• A livello epatico, il calo del DHA-PL diminuisce sia la beta-ossidazione perossisomale degli acidi grassi che l’attività della stearoil-coenzima A desaturasi; un calo d’attività di quest’ultimo enzima si è dimostrato strettamente correlato con l’aumento della steatosi epatica, dell’insulino- resistenza e del peso corporeo.
• A livello eritrocitario, infine, il calo di DHA-PL, promuovendo un irrigidimento della membrana rallenta le velocità di cessione dell’ossigeno ai diversi tessuti. Da qui, una diminuzione del metabolismo ossidativo e della termogenesi ed un aumento dell’infiammazione. Alla luce di tutte queste evidenze scientifiche si può dunque concludere che uno degli obiettivi più importanti da perseguire per assicurare il corretto funzionamento dei mediatori dell’asse “gut-brain”, atto a prevenire sia l’obesità che la sindrome metabolica, è quello di contrastare il calo del DHA-PL conseguente alla diminuzione di fluidità delle membrane ed all’aumento del Ca e dei processi d’infiammazione e di perossidazione ad esso correlati.
[1] D.A. Pan, A.J. Hulbert, L.H. Storlien, J Nutr 124 (1994) 1555-1565.
[2] A. Scalbert, G. Williamson, J Nutr 130 (2000) 2073S-2085S.
[3] R. Cazzola, M. Rondanelli, R. Trotti, B. Cestaro, J Nutr Biochem. Available online 8 July 2010 doi:10.1016/j.jnutbio.2010.03.00
Fluidità di membrana, ossidazione delle lipoproteine ed invecchiamento
No full textIn the past 20 years evidence has been accumulated suggesting that oxidative stress and damage to cellular components from reactive oxygen species (ROS) play an integral role in the age-related deterioration of biochemical and physiologic processes and in the incidence of age-related disease. Mitochondria are the primary site for ROS generation as a by product of aerobic metabolism and the accumulation of mitochondrial oxidative damage over time diminishes the cellular efficiency in energy production (ATP). Moreover, oxidative stress contributes to functional and structural alterations of tissues and blood vessels that decrease the supply of oxygen and nutrients to the various organs and body systems, thus further reducing energy production. The deficiency of ATP decreases the bioavailability of all the molecules whose biosynthesis requires the intervention of ATP itself and slows down the process of repair and replacement of the various lipid or glycoprotein molecules, which make up the bilayer structural organization of the cell membrane. Current evidence suggests that the processe at the cell surface seem to be of comparable importance for the life of an individual as the nucleus for the preservation of the species. Oxidative stress leads to progressive structural alteration of membranes manifested by a progressive reduction of membrane fluidity that causes a secondary metabolic damage to the cells. The membrane hardening, in fact, limits the capacity of membrane proteins to collide with their ligands, thus reducing the activity of enzymes, receptors for hormone or neurotransmitter, ion channels and the trans-membrane carriers for amino acids and glucose. There is thus a spiral of structural and functional damage to cells and tissues, starting with the reduced efficiency in ATP synthesis which is further amplified by the decreased rate of synthesis of membrane macromolecules and lipids, the increase in intracellular calcium and potassium, and the increase in ROS-induced peroxidation processes. Moreover, significant correlations have been found between lipoprotein susceptibility to peroxidation, the degree of obesity, the peripheral resistance to insulin, and the risk to developing atherosclerosis and cardiovascular diseases. In particular, in the case of HDL it has been demonstrated that these lipoproteins serve as an acceptor of cholesterol efflux from foam cells by a mechanism similar to that of “reverse cholesterol transport” and that their oxidation significantly reduces the cholesterol efflux from macrophage-derived foam cells. In a previous work we demonstrated that pyrene derivatives can be used to selectively follow the kinetics of Cu++-catalyzed peroxidation in the hydrophilic envelope (pyrene dodecanoyl sulfatide) and in the hydrophobic core (cholesteryl pyrenyl hexanoate) of human LDL and HDL. With the aim to provide more detailed information on the correlation between lipoprotein susceptibility to peroxidation, membrane fluidity, obesity and risk of developing atherosclerosis, we performed a study in which the different envelope and core susceptibility to peroxidation of both LDL and HDL and membrane fluidity were measured in two adult female groups: overweight and obese patients and lean healthy subjects. The response of the hydrophobic core to oxidative stress induced by Cu++ in LDL and HDL was quite similar in both groups, whereas the envelope, and in particular that one of HDL lipoproteins, was by far more rapidly peroxidized in overweight and obese patients. The higher oxidability of the HDL envelope of obese patients could depend on several factors, including the concentration of envelope-specific antioxidants, the levels of peroxidable substrates, and the different catalyzing capacity of copper. How both the onset of this ROS-induced spiral and the membrane hardening in the obese patients could be kept under control with either an adequate diet or a supply of appropriate functional food will be the main issue of this presentation
Red wine polyphenols protect n−3 more than n−6 polyunsaturated fatty acid from lipid peroxidation
No full textModerate red wine consumption is associated with decreased risk for cardiovascular disease; however, the underlying mechanisms are not completely understood. The main aim of this study was to investigate the effects of red wine polyphenols (WP) on the oxidizability of human plasma fatty acids, in particular those most involved in the inflammatory response — archidonic acid (AA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). The oxidizability of the major fatty acids of plasma was determined by measuring their loss gaschromatographycally during peroxidation kinetics induced by 2′-azobis(2-methylpropionamidine)-dihydrochloride. The capacity of WP to scavenge 1,1,diphenyl-2-picryl-hydrazyl (DPPH), superoxide anion and hydroxyl radicals, and trap total peroxyl radicals in plasma (TRAP) was also measured. WP (1.75–5 μg/mL) inhibited DPPH, superoxide anion and hydroxyl radicals and increased TRAP in a dose-dependent manner. WP (1.75 μg/mL) significantly protected all plasma PUFA from peroxidation but the protection of EPA and DHA was higher than that of AA. These results suggest that the association of WP to apolipoproteins makes EPA and DHA less accessible to hydro-soluble radicals than AA, thus providing a biochemical rationale for future ‘in vivo’ studies on the benefits to health of moderate red wine consumption
Impaired fluidity and oxidizability of HDL hydrophobic core and amphipathic surface in dyslipidemic men
No full textObjective: To examine and compare the composition, fluidity and oxidizability of HDL hydrophobic core and amphipathic surface of two groups of adult males (25kg/m(2)<BMI<30kg/m(2)), the former mixed dyslipidemic patients (MD) and the latter age- and BMI-matched healthy controls. Methods and results:
Pyrenyl-cholesteryl ester and pyrenyl-phosphatidylcholine, respectively incorporated in HDL core or surface were used for measuring both 2,2'-azobis-2-methyl-propanimidamide-dihydrochloride-induced peroxidation kinetics and fluidities of these regions. In comparison with the controls, MD HDL showed: a) higher free cholesterol to phospholipid ratio in surface and triacylglycerols to cholesteryl ester ratio in the core, b) higher malondialdehyde levels and lower alpha-tocopherol and beta-carotene to neutral lipid ratios, c) a more rigid surface and more fluid core, d) dramatically decreased lag-time and increased propagation rate of peroxidation kinetic in the core, but only an increased propagation rate on the surface. Conclusion: These results suggest that better knowledge of the physical-chemical properties and oxidizability of HDL core and surface could contribute to better understanding of the mechanisms connecting HDL alteration to increased risk of CDV in MD
Anti-oxidant, anti-glycant, and inhibitory activity against α-amylase and α-glucosidase of selected spices and culinary herbs
No full textAqueous and methanol extracts of dry sage, rosemary, basil, parsley, chili, garlic and onion were analyzed to investigate their
anti-oxidant and anti-glycant activities and in vitro inhibitory potential against enzymes involved in glycemic regulation.
The aqueous extracts of rosemary and sage were the richest in phenolic compounds and showed the highest ability in binding iron
and inhibiting DPPH, superoxide radicals and advanced glycation end-product production, lipid peroxidation, and the activity of
a-glucosidase and a-amylase. On the other hand, the methanol extracts of both these Labiatae were less efficient than those of
garlic, onion, parsley and chili in scavenging hydroxyl radicals. As far as protein glycation is concerned, methanol extracts were more effective in inhibiting the production of Amadori compounds and the aqueous ones in preventing advanced glycation endproduct formation. Therefore these spices may be preventive not only against cardiovascular diseases but also type 2 diabetes
Effects of weight loss on erythrocyte membrane composition and fluidity in overweight and moderately obese women
No full textA previous study showed chemical and physical impairment of the erythrocyte membrane of overweight and moderately obese women. The present study investigated the effects of a low-calorie diet (800 kcal/day deficit for 8 weeks) on erythrocyte membrane properties in 70 overweight and moderately obese (body mass index, 25-33 kg/m(2)) normotensive, nondiabetic women. At the end of dietary intervention, 24.3% of women dropped out, 45.7% lost less than 5% of their initial weight (Group I) and only 30% of patients lost at least 5% of their initial body weight (Group II). Group I showed no significant changes in erythrocyte membrane composition and function. The erythrocyte membranes of Group II showed significant reductions in malondialdehyde, lipofuscin, cholesterol, sphingomyelin, palmitic acid and nervonic acid and an increase in di-homo-gamma-linolenic acid, arachidonic acid and membrane fluidity. Moreover, Group II showed an improvement in total cholesterol, low-density lipoprotein cholesterol, glycemia and insulin resistance. These changes in erythrocyte membrane composition could reflect a virtuous cycle resulting from the reduction in insulin resistance associated with increased membrane fluidity that, in turn, results in a sequence of metabolic events that concur to further improve membrane fluidity
La supplementazione orale di acidi grassi n-3 e melatonina puo’ ridurre il declino cognitivo nei pazienti affetti da mild cognitive impairment
No full textKinetics of vibrio cholerae sialidase action on gangliosidic substrates at different supramolecular-organizational levels
No full textG(d1a), G(d1b) and G(t1b) gangliosides were dispersed in the following membrane-mimicking systems: (a) homogeneous micelles; (b) mixed micelles with G(m1) ganglioside (which is resistant to the enzyme action), Triton X-100 or bovine serum albumin; (c) small unilamellar vesicles of egg phosphatidylcholine. The effect of dispersion on sialic acid release by Vibrio cholerae sialidase was studied. As reference substrates freely interacting with the enzyme the lipid-free carbohydrates of G(d1a) and 3'-sialosyl-lactose were employed. The apparent V(max.) of the enzyme was, with all the gangliosides, dependent on the type of ganglioside dispersion. It was lowest for homogeneous micelles and mixed micelles with ganglioside G(m1), and increased about 6-fold for ganglioside/bovine serum albumin lipoprotein micelles, 15-fold for mixed-ganglioside/Triton X-100 micelles (optimal molar ratio 1:7.5) and 30-fold for phosphatidylcholine vesicles containing 2.5 mol% ganglioside (this proportion was optimal for enzyme activity on the vesicles). For ganglioside G(d1a), the activity on Triton X-100 mixed micelles and on mixed vesicles was even greater (3- and 6-fold respectively) than that displayed on G(d1a) lipid-free carbohydrate. With each of the used gangliosides the apparent K(m) values were very similar values for homogeneous micelles and vesicular dispersions, but showed marked increases for Triton X-100 mixed micelles, approaching the values exhibited by reference oligosaccharides. Triton X-100 micelles and phosphatidylcholine vesicles did not appreciably alter the kinetics of sialidase action on 3'-sialosyl-lactose and on G(d1a) lipid-free carbohydrate, indicating that the above effects are dependent on the intrinsic characteristics of the membrane-like systems containing gangliosides
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