RESUMO
The natural peptide somatostatin has hormonal and cytostatic effects exerted by the binding to specific receptors in various tissues. Therapeutic uses are strongly prevented by its very short biological half-life of 1-2 min due to enzymatic hydrolysis, therefore encapsulation methodologies are explored to overcome the need for continuous infusion regimes. Multilamellar liposomes made of natural phosphatidylcholine were used for the incorporation of a mixture of somatostatin and sorbitol dissolved in citrate buffer at pH = 5. Lyophilization and reconstitution of the suspension were carried out, showing the flexibility of this preparation. Full characterization of this suspension was obtained as particle size, encapsulation efficiency and retarded release properties in aqueous medium and human plasma. Liposomal somatostatin incubated at 37 °C in the presence of Fe(II) and (III) salts were used as a biomimetic model of drug-cell membrane interaction, evidencing the free radical processes of peroxidation and isomerization that transform the unsaturated fatty acid moieties of the lipid vesicles. This study offers new insights into a liposomal delivery system and highlights molecular reactivity of sulfur-containing drugs with its carrier or biological membranes for pharmacological applications.
Assuntos
Lipossomos/química , Somatostatina/química , Somatostatina/farmacologia , Soluções Tampão , Cromatografia Líquida , Preparações de Ação Retardada , Liberação Controlada de Fármacos , Radicais Livres/química , Humanos , Lipídeos/química , Espectrometria de Massas , Estrutura Molecular , Somatostatina/farmacocinéticaRESUMO
As the obesity epidemic continues to grow inexorably worldwide, the need to develop effective strategies to prevent and control obesity seems crucial. The use of molecular tools can be useful to characterize different obesity phenotypes to provide more precise nutritional recommendations. This study aimed to determine the fatty acid (FA) profile of red blood cell (RBC) membranes, together with the evaluation of their dietary intake and biochemical parameters, of children and adults with obesity. An observational study was carried out on 196 children (113 with normal weight and 83 with obesity) and 91 adults (30 with normal weight and 61 with obesity). Mature RBC membrane phospholipids were analyzed for FA composition by gas chromatography-mass spectrometry (GC-MS). Dietary habits were evaluated using validated food frequency questionnaires (FFQ). Children with obesity presented higher levels of ω-6 polyunsaturated FAs (mainly linoleic acid, p = 0.01) and lower values of ω-3 FAs (mainly DHA, p < 0.001) compared with adults. Regarding blood biochemical parameters, children with obesity presented lower levels of glucose, LDL cholesterol, and alanine aminotransferase compared with adults with obesity. These lipidomic differences could be considered to provide specific nutritional recommendations for different age groups, based on an adequate fat intake.
RESUMO
Obesity is a chronic metabolic disease of high complexity and of multifactorial origin. Understanding the effects of nutrition on childhood obesity metabolism remains a challenge. The aim of this study was to determine the fatty acid (FA) profile of red blood cell (RBC) membranes as a comprehensive biomarker of children's obesity metabolism, together with the evaluation of their dietary intake. An observational study was carried out on 209 children (107 healthy controls, 41 who were overweight and 61 with obesity) between 6 and 16 years of age. Mature RBC membrane phospholipids were analyzed for FA composition by gas chromatography-mass spectrometry (GC-MS). Dietary habits were evaluated using validated food frequency questionnaires (FFQ) and the Mediterranean Diet Quality Index for children (KIDMED) test. Compared to children with normal weight, children with obesity showed an inflammatory profile in mature RBC FAs, evidenced by higher levels of ω-6 polyunsaturated FAs (mainly arachidonic acid, p < 0.001). Children who were overweight or obese presented lower levels of monounsaturated FA (MUFA) compared to children with normal weight (p = 0.001 and p = 0.03, respectively), resulting in an increased saturated fatty acid (SFA)/MUFA ratio. A lower intake of nuts was observed for children with obesity. A comprehensive membrane lipidomic profile approach in children with obesity will contribute to a better understanding of the metabolic differences present in these individuals.
Assuntos
Membrana Eritrocítica/metabolismo , Ácidos Graxos Monoinsaturados/sangue , Ácidos Graxos/sangue , Obesidade Infantil/metabolismo , Fosfolipídeos/sangue , Adolescente , Biomarcadores/sangue , Criança , Ácidos Graxos Ômega-6/sangue , Comportamento Alimentar , Feminino , Humanos , Masculino , Sobrepeso/metabolismo , Estudos Retrospectivos , EspanhaRESUMO
During seed imbibition, lipids are engaged in membrane reorganization while facing free radical-mediated oxidative injury. In the present work, we explored changes in lipid components at different timepoints of imbibition (0.5, 2, 4, 6, and 8 h) in the legume Medicago truncatula, by combining biochemical approaches with targeted lipidomics and untargeted metabolomics. ROS and RNS (reactive oxygen and nitrogen species) accumulation was observed throughout the tested timepoints whereas lipid peroxidation increased at 4 h of imbibition. The seed response to oxidative damage was evidenced by a significant increase in tocopherols starting from 0.5 h of imbibition as well as by the reduction in total thiol content occurring at 2 h of imbibition. Since under physiological conditions, the proper functions of the cell membranes are strongly dependent on the qualitative and quantitative balance of fatty acid residues in phospholipids, the investigation was expanded to the fatty acid cohort of M. truncatula seeds. Total saturated fatty acids (SFAs), monounsaturated fatty acids (MUFAs), polyunsaturated fatty acids (PUFAs), omega(ω)-3 and omega(ω)-6 fatty acids showed fluctuations during seed imbibition. The most remarkable finding was the profile of the ω-3 PUFA docosopentaenoic acid (DPA, 7 cis, 10 cis, 13 cis, 16 cis, and 19 cis-22:5) that showed a peak (up to 1.0% of the total fatty acid content) at 0.5 and 8 h of imbibition, concomitant with the peaks observed in tocopherol levels. It is possible that the observed changes in DPA alter the physical properties of membranes, as reported in animal cells, triggering signaling pathways relevant for the cell defense against oxidative injury. Furthermore, the content and balance between tocopherols and PUFAs is regarded as a determinant of storage stability. No enhancement in trans-fatty acids occurred throughout imbibition, suggesting for a proper antioxidant response carried by the seed. Fatty acids profiles were integrated with data from untargeted metabolomics showing changes in lipid sub-pathways, among which fatty acid amide, lyso-phospholipids, and phospholipid metabolism. The emerging lipid profiles and dynamics are discussed in view of the overall imbibition damage generated during M. truncatula seed imbibition.
RESUMO
Fatty acids, as structural components of membranes and inflammation/anti-inflammatory mediators, have well-known protective and regulatory effects. They are studied as biomarkers of pathological conditions, as well as saturated and unsaturated hydrophobic moieties in membrane phospholipids that contribute to homeostasis and physiological functions. Lifestyle, nutrition, metabolism and stress-with an excess of radical and oxidative processes-cause fatty acid changes that are examined in the human body using blood lipids. Fatty acid-based membrane lipidomics represents a powerful diagnostic tool for assessing the quantity and quality of fatty acid constituents and also for the follow-up of the membrane fatty acid remodeling that is associated with different physiological and pathological conditions. This review focuses on fatty acid biomarkers with two examples of recent lipidomic research and health applications: (i) monounsaturated fatty acids and the analytical challenge offered by hexadecenoic fatty acids (C16:1); and (ii) the cohort of 10 fatty acids in phospholipids of red blood cell membranes and its connections to metabolic and nutritional status in healthy and diseased subjects.