RESUMEN
Fucoidans are a diverse class of sulfated polysaccharides integral to the cell wall of brown algae, and due to their various bioactivities, they are potential drugs. Standardized work with fucoidans is required for structure-function studies, but remains challenging since available fucoidan preparations are often contaminated with other algal compounds. Additionally, fucoidans are structurally diverse depending on species and season, urging the need for standardized purification protocols. Here, we use ion-exchange chromatography to purify different fucoidans and found a high structural diversity between fucoidans. Ion-exchange chromatography efficiently removes the polysaccharides alginate and laminarin and other contaminants such as proteins and phlorotannins across a broad range of fucoidans from major brown algal orders including Ectocarpales, Laminariales and Fucales. By monomer composition, linkage analysis and NMR characterization, we identified galacturonic acid, glucuronic acid and O-acetylation as new structural features of certain fucoidans and provided a novel structure of fucoidan from Durvillaea potatorum with α-1,3-linked fucose backbone and ß-1,6 and ß-1,3 galactose branches. This study emphasizes the use of standardized ion-exchange chromatography to obtain defined fucoidans for subsequent molecular studies.
Asunto(s)
Phaeophyceae , Sulfatos , Fucosa , Polisacáridos/química , Sulfatos/químicaRESUMEN
Excessive energy intake leads to fat overload and the formation of lipotoxic compounds mainly derived from the saturated fatty acid palmitate (PAL), thus promoting insulin resistance (IR) in skeletal muscle. N-3 polyunsaturated fatty acids (n-3PUFA) may prevent lipotoxicity and IR. The purpose of this study was to examine the differential effects of n-3PUFA on fatty acid metabolism and insulin sensitivity in muscle cells. C2C12 myotubes were treated with 500 µM of PAL without or with 50 µM of alpha-linolenic acid (ALA), eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA) for 16 h. PAL decreased insulin-dependent AKT activation and glucose uptake and increased the synthesis of ceramides and diglycerides (DG) derivatives, leading to protein kinase Cθ activation. EPA and DHA, but not ALA, prevented PAL-decreased AKT activation but glucose uptake was restored to control values by all n-3PUFA vs. PAL. Total DG and ceramide contents were decreased by all n-3PUFA, but only EPA and DHA increased PAL ß-oxidation, decreased PAL incorporation into DG and reduced protein kinase Cθ activation. EPA and DHA emerge as better candidates than ALA to improve fatty acid metabolism in skeletal muscle cells, notably via their ability to increase mitochondrial ß-oxidation.
Asunto(s)
Ácidos Grasos Omega-3/farmacología , Mioblastos Esqueléticos/efectos de los fármacos , Palmitatos/toxicidad , Animales , Células Cultivadas , Ácidos Grasos/metabolismo , Glucosa/metabolismo , Resistencia a la Insulina , Isoenzimas/fisiología , Fluidez de la Membrana/efectos de los fármacos , Ratones , Mioblastos Esqueléticos/metabolismo , Fosforilación , Proteína Quinasa C/fisiología , Proteína Quinasa C-thetaRESUMEN
The impact of alpha linolenic acid (ALA), EPA, and DHA on obesity and metabolic complications was studied in mice fed a high-fat, high-sucrose (HF) diet. HF diets were supplemented with ALA, EPA, or DHA (1% w/w) and given to C57BL/6J mice for 16 weeks and to Ob/Ob mice for 6 weeks. In C57BL/6J mice, EPA reduced plasma cholesterol (-20%), limited fat mass accumulation (-23%) and adipose cell hypertrophy (-50%), and reduced plasma leptin concentration (-60%) compared with HF-fed mice. Furthermore, mice supplemented with EPA exhibited a higher insulin sensitivity (+24%) and glucose tolerance (+20%) compared with HF-fed mice. Similar effects were observed in EPA-supplemented Ob/Ob mice, although fat mass accumulation was not prevented. By contrast, in comparison with HF-fed mice, DHA did not prevent fat mass accumulation, increased plasma leptin concentration (+128%) in C57BL/6J mice, and did not improve glucose homeostasis in C57BL/6J and Ob/Ob mice. In 3T3-L1 adipocytes, DHA stimulated leptin expression whereas EPA induced adiponectin expression, suggesting that improved leptin/adiponectin balance may contribute to the protective effect of EPA. In conclusion, supplementation with EPA, but not ALA and DHA, could preserve glucose homeostasis in an obesogenic environment and limit fat mass accumulation in the early stage of weight gain.
Asunto(s)
Tejido Adiposo Blanco/patología , Fármacos Antiobesidad/farmacología , Dieta Occidental/efectos adversos , Ácido Eicosapentaenoico/farmacología , Obesidad/metabolismo , Células 3T3-L1 , Adipogénesis , Adipoquinas/metabolismo , Tejido Adiposo Blanco/efectos de los fármacos , Tejido Adiposo Blanco/metabolismo , Adiposidad/efectos de los fármacos , Animales , Membrana Celular/metabolismo , Evaluación Preclínica de Medicamentos , Eritrocitos/metabolismo , Expresión Génica , Intolerancia a la Glucosa , Resistencia a la Insulina , Leptina/genética , Leptina/metabolismo , Metabolismo de los Lípidos/efectos de los fármacos , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Obesos , Obesidad/tratamiento farmacológico , Obesidad/etiología , Fosfolípidos/metabolismoRESUMEN
Decline in skeletal muscle mass and function starts during adulthood. Among the causes, modifications of the mitochondrial function could be of major importance. Polyunsaturated fatty (ω-3) acids have been shown to play a role in intracellular functions. We hypothesize that docosahexaenoic acid (DHA) supplementation could improve muscle mitochondrial function that could contribute to limit the early consequences of aging on adult muscle. Twelve-month-old male Wistar rats were fed a low-polyunsaturated fat diet and were given DHA (DHA group) or placebo (control group) for 9 wk. Rats from the DHA group showed a higher endurance capacity (+56%, P < 0.05) compared with control animals. Permeabilized myofibers from soleus muscle showed higher O2 consumptions (P < 0.05) in the DHA group compared with the control group, with glutamate-malate as substrates, both in basal conditions (i.e., state 2) and under maximal conditions (i.e., state 3, using ADP), along with a higher apparent Km for ADP (P < 0.05). Calcium retention capacity of isolated mitochondria was lower in DHA group compared with the control group (P < 0.05). Phospho-AMPK/AMPK ratio and PPARδ mRNA content were higher in the DHA group compared with the control group (P < 0.05). Results showed that DHA enhanced endurance capacity in adult animals, a beneficial effect potentially resulting from improvement in mitochondrial function, as suggested by our results on permeabilized fibers. DHA supplementation could be of potential interest for the muscle function in adults and for fighting the decline in exercise tolerance with age that could imply energy-sensing pathway, as suggested by changes in phospho-AMPK/AMPK ratio.
Asunto(s)
Membrana Celular/efectos de los fármacos , Suplementos Dietéticos , Ácidos Docosahexaenoicos/farmacología , Tolerancia al Ejercicio/efectos de los fármacos , Mitocondrias Musculares/efectos de los fármacos , Músculo Esquelético/efectos de los fármacos , Resistencia Física/efectos de los fármacos , ARN Mensajero/efectos de los fármacos , 3-Hidroxiacil-CoA Deshidrogenasas/efectos de los fármacos , 3-Hidroxiacil-CoA Deshidrogenasas/metabolismo , Animales , Western Blotting , Calcio/metabolismo , Calorimetría Indirecta , Membrana Celular/metabolismo , Colesterol/metabolismo , Citrato (si)-Sintasa/efectos de los fármacos , Citrato (si)-Sintasa/metabolismo , Transporte de Electrón/efectos de los fármacos , Peróxido de Hidrógeno/metabolismo , Masculino , Mitocondrias Musculares/metabolismo , Fibras Musculares Esqueléticas/efectos de los fármacos , Fibras Musculares Esqueléticas/metabolismo , Músculo Esquelético/metabolismo , Consumo de Oxígeno/efectos de los fármacos , Fosfolípidos/metabolismo , Condicionamiento Físico Animal , ARN Mensajero/metabolismo , Ratas , Ratas Wistar , Reacción en Cadena en Tiempo Real de la Polimerasa , Triglicéridos/metabolismoRESUMEN
BACKGROUND: Saturated fatty acid-rich high fat (HF) diets trigger abdominal adiposity, insulin resistance, type 2 diabetes and cardiac dysfunction. This study was aimed at evaluating the effects of nascent obesity on the cardiac function of animals fed a high-fat diet and at analyzing the mechanisms by which these alterations occurred at the level of coronary reserve. MATERIALS AND METHODS: Rats were fed a control (C) or a HF diet containing high proportions of saturated fatty acids for 3 months. Thereafter, their cardiac function was evaluated in vivo using a pressure probe inserted into the cavity of the left ventricle. Their heart was isolated, perfused iso-volumetrically according to the Langendorff mode and the coronary reserve was evaluated by determining the endothelial-dependent (EDV) and endothelial-independent (EIV) vasodilatations in the absence and presence of endothelial nitric oxide synthase and cyclooxygenase inhibitors (L-NAME and indomethacin). The fatty acid composition of cardiac phospholipids was then evaluated. RESULTS: Although all the HF-fed rats increased their abdominal adiposity, some of them did not gain body weight (HF- group) compared to the C group whereas other ones had a higher body weight (HF+). All HF rats displayed a higher in vivo cardiac activity associated with an increased EDV. In the HF- group, the improved EDV was due to an increase in the endothelial cell vasodilatation activity whereas in the HF+ group, the enhanced EDV resulted from an improved sensitivity of coronary smooth muscle cells to nitric oxide. Furthermore, in the HF- group the main pathway implicated in the EDV was the NOS pathway while in the HF+ group the COX pathway. CONCLUSIONS: Nascent obesity-induced improvement of cardiac function may be supported by an enhanced coronary reserve occurring via different mechanisms. These mechanisms implicate either the endothelial cells activity or the smooth muscle cells sensitivity depending on the body adiposity of the animals.
Asunto(s)
Adiposidad/fisiología , Vasos Coronarios/fisiología , Dieta Alta en Grasa/efectos adversos , Obesidad/fisiopatología , Vasodilatación/fisiología , Animales , Vasos Coronarios/citología , Masculino , Obesidad/metabolismo , Distribución Aleatoria , Ratas , Ratas WistarRESUMEN
BACKGROUND: There has been accumulating evidence associating diabetes mellitus and cardiovascular dysfunctions. However, most of the studies are focused on the late stages of diabetes and on the function of large arteries. This study aimed at characterizing the effects of the early phase of diabetes mellitus on the cardiac and vascular function with focus on the intact coronary microvasculature and the oxidative stress involved. MATERIALS AND METHODS: Zucker diabetic fatty rats and their lean littermates fed with standard diet A04 (Safe) were studied at the 11th week of age. Biochemical parameters such as glucose, insulin and triglycerides levels as well as their oxidative stress status were measured. Their hearts were perfused ex vivo according to Langendorff and their cardiac activity and coronary microvascular reactivity were evaluated. RESULTS: Zucker fatty rats already exhibited a diabetic state at this age as demonstrated by the elevated levels of plasma glucose, insulin, glycated hemoglobin and triglycerides. The ex vivo perfusion of their hearts revealed a decreased cardiac mechanical function and coronary flow. This was accompanied by an increase in the overall oxidative stress of the organs. However, estimation of the active form of endothelial nitric oxide synthase and coronary reactivity indicated a preserved function of the coronary microvessels at this phase of the disease. Diabetes affected also the cardiac membrane phospholipid fatty acid composition by increasing the arachidonic acid and n-3 polyunsaturated fatty acids levels. CONCLUSIONS: The presence of diabetes, even at its beginning, significantly increased the overall oxidative stress of the organs resulting to decreased cardiac mechanical activity ex vivo. However, adaptations were adopted at this early phase of the disease regarding the preserved coronary microvascular reactivity and the associated cardiac phospholipid composition in order to provide a certain protection to the heart.
Asunto(s)
Diabetes Mellitus Experimental/fisiopatología , Endotelio Vascular/fisiología , Corazón/fisiología , Microvasos/fisiología , Estrés Oxidativo/fisiología , Vasodilatación/fisiología , Animales , Circulación Coronaria/fisiología , Diabetes Mellitus Experimental/metabolismo , Masculino , Técnicas de Cultivo de Órganos , Ratas , Ratas Zucker , Factores de TiempoRESUMEN
Long-chain (LC) n-3 PUFA have a broad range of biological properties that can be achieved at the gene expression level. This has been well described in liver, where LC n-3 PUFA modulate the expression of genes related to lipid metabolism. However, the complexity of biological pathway modulations and the nature of bioactive molecules are still under investigation. The present study aimed to investigate the dose-response effects of LC n-3 PUFA on the production of peroxidised metabolites, as potential bioactive molecules, and on global gene expression in liver. Hypercholesterolaemic rabbits received by daily oral administration (7 weeks) either oleic acid-rich oil or a mixture of oils providing 0.1, 0.5 or 1 % (groups 1, 2 and 3 respectively) of energy as DHA. Levels of specific peroxidised metabolites, namely 4-hydroxyhexenal (4-HHE)-protein adducts, issued from LC n-3 PUFA were measured by GC/MS/MS in liver in parallel to transcription profiling. The intake of LC n-3 PUFA increased, in a dose-dependent manner, the hepatic production of 4-HHE. At the highest dose, LC n-3 PUFA provoked an accumulation of TAG in liver, which can be directly linked to increased mRNA levels of lipoprotein hepatic receptors (LDL-receptor and VLDL-receptor). In groups 1 and 2, the mRNA levels of microsomal TAG transfer protein decreased, suggesting a possible new mechanism to reduce VLDL secretion. These modulations of genes related to lipoprotein metabolism were independent of PPARα signalling but were probably linked to the activation of the farnesol X receptor pathway by LC n-3 PUFA and/or their metabolites such as HHE.
Asunto(s)
Ácidos Grasos Omega-3/metabolismo , Regulación de la Expresión Génica , Peroxidación de Lípido , Hígado/metabolismo , Administración Oral , Aldehídos/metabolismo , Animales , Relación Dosis-Respuesta a Droga , Cromatografía de Gases y Espectrometría de Masas , Perfilación de la Expresión Génica , Hipercolesterolemia/tratamiento farmacológico , Metabolismo de los Lípidos , Microsomas Hepáticos/metabolismo , Conejos , Receptores Citoplasmáticos y Nucleares/metabolismo , Espectrometría de Masas en TándemRESUMEN
BACKGROUND: The effects of a dietary supplementation with the vegetable ω-3 α-linolenic acid (ALA) on cardiovascular homeostasis are unclear. In this context, it would be interesting to assess the effects of camelina oil. OBJECTIVE: This study aimed to assess the cardiovascular and metabolic effects of camelina oil in hypertensive patients with metabolic syndrome. METHODS: In a double-blind, placebo-controlled randomized study, treated essential hypertensive patients with metabolic syndrome received, during 6 mo, either cyclodextrin-complexed camelina oil containing ≈ 1.5 g ALA/d (n = 40) or an isocaloric placebo (n = 41), consisting of the same quantity of cyclodextrins and wheat starch. Anthropometric data, plasma lipids, glycemia, insulinemia, creatininemia, TBARs, high-sensitivity C-reactive protein, and n-3, n-6, and n-9 fatty acids in erythrocyte membranes were measured. Peripheral and central blood pressures, arterial stiffness, carotid intima-media thickness, and brachial artery endothelium-dependent flow-mediated dilatation (FMD) and endothelium-independent dilatation were assessed. RESULTS: Compared with placebo, camelina oil increased ALA (mean ± SD: 0 ± 0.04 compared with 0.08 ± 0.06%, P <0.001), its elongation product EPA (0 ± 0.5 compared with 0.16 ± 0.65%, P <0.05), and the n-9 gondoic acid (GA; 0 ± 0.04 compared with 0.08 ± 0.04%, P <0.001). No between-group difference was observed for cardiovascular parameters. However, changes in FMD were associated with the magnitude of changes in EPA (r = 0.26, P = 0.03). Compared with placebo, camelina oil increased fasting glycemia (-0.2 ± 0.6 compared with 0.3 ± 0.5 mmol/L, P <0.001) and HOMA-IR index (-0.8 ± 2.5 compared with 0.5 ± 0.9, P <0.01), without affecting plasma lipids, or inflammatory and oxidative stress markers. Changes in HOMA-IR index were correlated with the magnitude of changes in GA (r = 0.32, P <0.01). Nutritional intake remained similar between groups. CONCLUSION: ALA supplementation with camelina oil did not improve vascular function but adversely affected glucose metabolism in hypertensive patients with metabolic syndrome. Whether this adverse effect on insulin sensitivity is related to GA enrichment, remains to be elucidated.
Asunto(s)
Ácidos Grasos Omega-3 , Hipertensión , Síndrome Metabólico , Grosor Intima-Media Carotídeo , Método Doble Ciego , Ácidos Grasos Omega-3/farmacología , Humanos , Hipertensión/tratamiento farmacológico , Síndrome Metabólico/tratamiento farmacológicoRESUMEN
The viscoelastic mechanical properties are important quality traits for fleshy fruit uses. The contribution of cell wall polysaccharides chemistry and organization on their variability was studied in six varieties of apple. Correlation between damping and storage modulus of plasmolyzed tissue distinguished better apple varieties on their viscoelasticity than fresh samples. Galactose, arabinose and uronic acids correlated positively with the storage modulus of fresh apple samples (E'f). These corresponded to 4-linked galactan but no specific arabinose linkage. Galacturonic acid branched on O-3 and terminal rhamnose correlated negatively with E'f. These correlations formed two groups of fruit except for branched methyl-esterified galacturonic. Solid-state 13C NMR spectroscopy analyses showed that E'f correlated negatively with cellulose C4 T1ρH relaxation and positively with pectin methyl esters THH proton diffusion. The results point to the key roles of pectin structure and hydration and cellulose microfibrils distribution on apple mechanical properties.
Asunto(s)
Pared Celular/química , Celulosa/análisis , Frutas/química , Malus/química , Pectinas/análisis , Agua/análisis , Tamaño de la Partícula , Propiedades de Superficie , ViscosidadRESUMEN
Mammalian spermatozoa undergo important plasma membrane maturation steps during epididymal transit. Among these, changes in lipids and cholesterol are of particular interest as they are necessary for fertilization. However, molecular mechanisms regulating these transformations inside the epididymis are still poorly understood. Liver X receptors (LXRs), the nuclear receptors for oxysterols, are of major importance in intracellular cholesterol homeostasis, and LXR(-/-)-deficient male mice have already been shown to have reduced fertility at an age of 5 months and complete sterility for 9-month-old animals. This sterility phenotype is associated with testes and caput epididymides epithelial defects. The research presented here was aimed at investigating how LXRs act in the male caput epididymidis by analyzing key actors in cholesterol homeostasis. We show that accumulation of cholesteryl esters in LXR(-/-) male mice is associated with a specific loss of ABCA1 and an increase in apoptosis of apical cells of the proximal caput epididymidis. ATP-binding cassette G1 (ABCG1) and scavenger receptor B1 (SR-B1), two other cholesterol transporters, show little if any modifications. Our study also revealed that SR-B1 appears to have a peculiar expression pattern along the epididymal duct. These results should help in understanding the functional roles of LXR in cholesterol trafficking processes in caput epididymidis.
Asunto(s)
Transportadoras de Casetes de Unión a ATP/metabolismo , Colesterol/metabolismo , Epidídimo/metabolismo , Epidídimo/patología , Homeostasis , Receptores Nucleares Huérfanos/metabolismo , Transportador 1 de Casete de Unión a ATP , Animales , Apoptosis , Transporte Biológico , Colesterol/biosíntesis , Colesterol/química , Ésteres del Colesterol/metabolismo , Epidídimo/fisiopatología , Células Epiteliales/patología , Ácidos Grasos/metabolismo , Fertilidad , Receptores X del Hígado , Masculino , Ratones , Especificidad de Órganos , Maduración del EspermaRESUMEN
BACKGROUND: Blood polyunsaturated fatty acid (PUFA) levels are determined by diet and by endogenous synthesis via Δ5- and Δ6-desaturases (encoded by the FADS1 and FADS2 genes, respectively). Genome-wide association studies have reported associations between FADS1-FADS2 polymorphisms and the plasma concentrations of PUFAs, HDL- and LDL-cholesterol, and triglycerides. However, much remains unknown regarding the molecular mechanisms explaining how variants affect the function of FADS1-FADS2 genes. OBJECTIVE: Here, we sought to identify the functional variant(s) within the FADS gene cluster. METHODS: To address this question, we (1) genotyped individuals (n = 540) for the rs174547 polymorphism to confirm associations with PUFA levels used as surrogate estimates of desaturase activities and (2) examined the functionality of variants in linkage disequilibrium with rs174547 using bioinformatics and luciferase reporter assays. RESULTS: The rs174547 minor allele was associated with higher erythrocyte levels of dihomo-γ-linolenic acid and lower levels of arachidonic acid, suggesting a lower Δ5-desaturase activity. In silico analyses suggested that rs174545 and rs174546, in perfect linkage disequilibrium with rs174547, might alter miRNA binding sites in the FADS1 3'UTR. In HuH7 and HepG2 cells transfected with FADS1 3'UTR luciferase vectors, the haplotype constructs bearing the rs174546T minor allele showed 30% less luciferase activity. This relative decrease reached 60% in the presence of miR-149-5p and was partly abolished by cotransfection with an miR-149-5p inhibitor. CONCLUSION: This study identifies FADS1 rs174546 as a functional variant that may explain the associations between FADS1-FADS2 polymorphisms and lipid-related phenotypes.
Asunto(s)
Regiones no Traducidas 3'/genética , Eritrocitos/metabolismo , Ácido Graso Desaturasas/genética , Ácidos Grasos Omega-6/metabolismo , Polimorfismo de Nucleótido Simple , Adulto , Anciano , Alelos , Secuencia de Bases , Biología Computacional , delta-5 Desaturasa de Ácido Graso , Regulación hacia Abajo/genética , Femenino , Células Hep G2 , Humanos , Masculino , MicroARNs/genética , Persona de Mediana Edad , Familia de Multigenes/genética , FenotipoRESUMEN
BACKGROUND/AIMS: Human gut microbiota harbors numerous metabolic properties essential for the host's health. Increased intestinal transit time affects a part of the population and is notably observed with human aging, which also corresponds to modifications of the gut microbiota. Thus we tested the metabolic and compositional changes of a human gut microbiota induced by an increased transit time simulated in vitro. METHODS: The in vitro system, Environmental Control System for Intestinal Microbiota, was used to simulate the environmental conditions of 3 different anatomical parts of the human colon in a continuous process. The retention times of the chemostat conditions were established to correspond to a typical transit time of 48 hours next increased to 96 hours. The bacterial communities, short chain fatty acids and metabolite fingerprints were determined. RESULTS: Increase of transit time resulted in a decrease of biomass and of diversity in the more distal compartments. Short chain fatty acid analyses and metabolite fingerprinting revealed increased activity corresponding to carbohydrate fermentation in the proximal compartments while protein fermentations were increased in the lower parts. CONCLUSIONS: This study provides the evidence that the increase of transit time, independently of other factors, affects the composition and metabolism of the gut microbiota. The transit time is one of the factors that explain some of the modifications seen in the gut microbiota of the elderly, as well as patients with slow transit time.
RESUMEN
BACKGROUND: Muscle wasting prevails in numerous diseases (e.g. diabetes, cardiovascular and kidney diseases, COPD, ) and increases healthcare costs. A major clinical issue is to devise new strategies preventing muscle wasting. We hypothesized that 8-week docosahexaenoic acid (DHA) supplementation prior to fasting may preserve muscle mass in vivo. METHODS: Six-week-old C57BL/6 mice were fed a DHA-enriched or a control diet for 8 weeks and then fasted for 48 h. RESULTS: Feeding mice a DHA-enriched diet prior to fasting elevated muscle glycogen contents, reduced muscle wasting, blocked the 55% decrease in Akt phosphorylation, and reduced by 30-40% the activation of AMPK, ubiquitination, or autophagy. The DHA-enriched diet fully abolished the fasting induced-messenger RNA (mRNA) over-expression of the endocannabinoid receptor-1. Finally, DHA prevented or modulated the fasting-dependent increase in muscle mRNA levels for Rab18, PLD1, and perilipins, which determine the formation and fate of lipid droplets, in parallel with muscle sparing. CONCLUSIONS: These data suggest that 8-week DHA supplementation increased energy stores that can be efficiently mobilized, and thus preserved muscle mass in response to fasting through the regulation of Akt- and AMPK-dependent signalling pathways for reducing proteolysis activation. Whether a nutritional strategy aiming at increasing energy status may shorten recovery periods in clinical settings remains to be tested.
Asunto(s)
Suplementos Dietéticos , Ácidos Docosahexaenoicos/administración & dosificación , Ayuno/metabolismo , Atrofia Muscular/metabolismo , Adenosina Trifosfato/metabolismo , Animales , Modelos Animales de Enfermedad , Endocannabinoides/metabolismo , Ácidos Grasos/metabolismo , Regulación de la Expresión Génica/efectos de los fármacos , Glucógeno/metabolismo , Gotas Lipídicas/metabolismo , Metabolismo de los Lípidos , Ratones , Proteínas Quinasas Activadas por Mitógenos/metabolismo , Atrofia Muscular/genética , Atrofia Muscular/patología , Atrofia Muscular/prevención & control , Tamaño de los Órganos , Complejo de la Endopetidasa Proteasomal/metabolismo , Proteolisis , Proteínas Proto-Oncogénicas c-akt/metabolismo , Transducción de Señal , Ubiquitina/metabolismo , Ubiquitinación/efectos de los fármacosRESUMEN
Abdominal obesity increases the incidence of cardiac events but reduces mortality when one of these events occurs. The phenomenon called obesity paradox might be related to myocardial energetics. This study was aimed at determining whether long-term abdominal adiposity alters cardiac energy function. Two groups of male Wistar rats were fed a standard or a Western-type (WD) diet for 8 months. The ex vivo coronary reactivity and mechanical function as well as the mitochondrial oxidative phosphorylation (mOxPhos) and hydrogen peroxide release (mH2O2r) were determined. Abdominal adiposity was augmented by the WD. This was also the case for the coronary reactivity to acetylcholine, but the rate pressure product remained roughly stable despite a reduction of the left ventricle-developed pressure partly compensated by a slight increase in heart rate. The prolonged WD administration resulted in an improvement of mOxPhos, but the mH2O2r was exaggerated which was confirmed in the whole cell by a reduced aconitase to fumarase ratio. This did not modify the plasma oxidative stress due to an increased plasma antioxidant status. In conclusion, long-term WD administration improved the cardiac fitness and might predispose the organism to the obesity paradox. Conversely, the increased mitochondrial mH2O2r can precipitate the heart toward cardiomyopathy if the WD is maintained for a longer duration.
Asunto(s)
Adiposidad , Envejecimiento , Cardiomiopatías/etiología , Metabolismo Energético , Corazón/fisiopatología , Miocardio/metabolismo , Obesidad Abdominal/metabolismo , Aconitato Hidratasa/metabolismo , Alostasis , Animales , Cardiomiopatías/fisiopatología , Dieta Occidental/efectos adversos , Progresión de la Enfermedad , Fumarato Hidratasa/metabolismo , Frecuencia Cardíaca , Peróxido de Hidrógeno/metabolismo , Masculino , Miocardio/enzimología , Obesidad Abdominal/sangre , Obesidad Abdominal/etiología , Obesidad Abdominal/fisiopatología , Fosforilación Oxidativa , Estrés Oxidativo , Distribución Aleatoria , Ratas Wistar , Índice de Severidad de la Enfermedad , Taquicardia/etiologíaRESUMEN
Skeletal muscle plays a major role in the control of whole body glucose disposal in response to insulin stimulus. Excessive supply of fatty acids to this tissue triggers cellular and molecular disturbances leading to lipotoxicity, inflammation, mitochondrial dysfunctions, impaired insulin response and decreased glucose uptake. This study was conducted to analyze the preventive effect of docosahexaenoic acid (DHA), a long-chain polyunsaturated n-3 fatty acid, against insulin resistance, lipotoxicity and inflammation in skeletal muscle at doses compatible with nutritional supplementation. DHA (30 µM) prevented insulin resistance in C2C12 myotubes exposed to palmitate (500 µM) by decreasing protein kinase C (PKC)-θ activation and restoring cellular acylcarnitine profile, insulin-dependent AKT phosphorylation and glucose uptake. Furthermore, DHA protected C2C12 myotubes from palmitate- or lipopolysaccharide-induced increase in Ptgs2, interleukin 6 and tumor necrosis factor-α mRNA level, probably through the inhibition of p38 MAP kinase and c-Jun amino-terminal kinase. In LDLR -/- mice fed a high-cholesterol-high-sucrose diet, supplementation with DHA reaching up to 2% of daily energy intake enhanced the insulin-dependent AKT phosphorylation and reduced the PKC-θ activation in skeletal muscle. Therefore, DHA used at physiological doses participates in the regulation of muscle lipid and glucose metabolisms by preventing lipotoxicity and inflammation.
Asunto(s)
Suplementos Dietéticos , Ácidos Docosahexaenoicos/uso terapéutico , Aceites de Pescado/uso terapéutico , Resistencia a la Insulina , Metabolismo de los Lípidos , Músculo Esquelético/metabolismo , Miositis/prevención & control , Absorción Fisiológica , Animales , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/inmunología , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/prevención & control , Dieta Occidental/efectos adversos , Ácidos Docosahexaenoicos/administración & dosificación , Ácidos Docosahexaenoicos/metabolismo , Aceites de Pescado/administración & dosificación , Glucosa/metabolismo , Miembro Posterior , Isoenzimas/antagonistas & inhibidores , Isoenzimas/metabolismo , Ratones , Ratones Noqueados , Músculo Esquelético/enzimología , Músculo Esquelético/inmunología , Miositis/sangre , Miositis/inmunología , Miositis/metabolismo , Fosforilación , Proteína Quinasa C/antagonistas & inhibidores , Proteína Quinasa C/metabolismo , Proteína Quinasa C-theta , Procesamiento Proteico-Postraduccional , Proteínas Proto-Oncogénicas c-akt/agonistas , Proteínas Proto-Oncogénicas c-akt/metabolismo , Receptores de LDL/genética , Receptores de LDL/metabolismo , AtúnRESUMEN
BACKGROUND: Food frequency questionnaires (FFQs) are often used to evaluate individuals' food intakes in epidemiologic studies because of their simplicity and low cost. OBJECTIVE: To assess the validity of a short (24 items), qualitative FFQ used in the MONA LISA-NUT study. DESIGN: Cross-sectional study of a representative sample in three French counties. PARTICIPANTS/SETTING: The sample included 2,630 participants aged 35 to 65 years from the MONA LISA-NUT study. MAIN OUTCOME MEASURES: Food consumption was measured with the FFQ and via food records for 3 consecutive days. Plasma fatty acids were measured from a subset of participants. STATISTICAL ANALYSES PERFORMED: The FFQ items' validity was assessed by calculating crude and deattenuated Pearson correlation coefficients between frequencies reported by the FFQ and average weights reported by the food records. Furthermore, the validity of some items of the FFQ measuring the consumption of fatty foods was assessed by calculating Pearson correlation coefficients between frequencies of consumption of these foods and dosages of the corresponding plasma fatty acids: fish and eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), olive oil and oleic acid, margarine and elaidic acid, and dairy products and pentadecanoic and heptadecanoic acids. RESULTS: The mean of the deattenuated Pearson correlation coefficients for all items was 0.46, with values ranging from 0.22 (fried food) to 0.77 (breakfast cereal). The correlation coefficient was ≤ 0.4 for one third of the 24 items. Moderate correlations were found between fish and EPA/DHA (EPA: r=0.43, 95% CI 0.33 to 0.51; DHA: r=0.39, 95% CI 0.30 to 0.47), but not for other food items. CONCLUSIONS: One third of the 24 items in the short, qualitative FFQ evaluated here were not sufficiently valid. However, for the food groups most commonly studied in the literature, this FFQ had the same degree of validity as other questionnaires designed to classify subjects according to their level of intake.
Asunto(s)
Encuestas sobre Dietas , Conducta Alimentaria , Encuestas y Cuestionarios , Adulto , Anciano , Biomarcadores/sangre , Índice de Masa Corporal , Estudios Transversales , Productos Lácteos , Registros de Dieta , Grasas de la Dieta/administración & dosificación , Ácidos Docosahexaenoicos/administración & dosificación , Ácidos Docosahexaenoicos/sangre , Grano Comestible , Ácido Eicosapentaenoico/administración & dosificación , Ácido Eicosapentaenoico/sangre , Femenino , Francia , Frutas , Humanos , Masculino , Carne , Persona de Mediana Edad , Verduras , Población BlancaRESUMEN
n-3 polyunsaturated fatty acids (omega-3) supplementation is associated with reduced cardiovascular mortality and post-infarction death. However, the impact of omega-3 supplementation in congestive heart failure (CHF) is still unknown. This study assesses the effects of omega-3 supplementation on left ventricular (LV) function and remodelling. We assessed, in rats with CHF induced by left coronary ligation, the effects of a 1-week and a 12-week supplementation with omega-3 (450 mg/kg per day) on LV hemodynamics, function and structure. Chronic omega-3 reduces total peripheral resistance due to an increase in cardiac output without modification of arterial pressure. Only chronic omega-3 reduces LV end-diastolic pressure and LV relaxation constant. Moreover, chronic omega-3 decreases LV systolic and diastolic diameters, LV weight and collagen density. Acute and chronic omega-3 increase LV γ-glutamyl-cysteine synthetase and oppose glutathione deficiency resulting in a reduction of myocardial oxidized glutathione. In experimental CHF, long-term omega-3 supplementation improves LV hemodynamics and function and prevents LV remodelling and glutathione deficiency. The latter might be one of the mechanisms involved, but whether other mechanism, independent of myocardial redox 'status', such as reduced inflammation, are implicated remains to be confirmed.
Asunto(s)
Ácidos Grasos Omega-3/farmacología , Glutatión/deficiencia , Glutatión/metabolismo , Insuficiencia Cardíaca/tratamiento farmacológico , Insuficiencia Cardíaca/metabolismo , Remodelación Ventricular/efectos de los fármacos , Animales , Presión Sanguínea/efectos de los fármacos , Gasto Cardíaco/efectos de los fármacos , Vasos Coronarios/efectos de los fármacos , Suplementos Dietéticos , Eritrocitos/metabolismo , Ácidos Grasos Omega-3/sangre , Glutamato-Cisteína Ligasa/metabolismo , Corazón/efectos de los fármacos , Insuficiencia Cardíaca/patología , Hemodinámica/efectos de los fármacos , Hígado/metabolismo , Masculino , Miocardio/metabolismo , Estrés Oxidativo/efectos de los fármacos , Ratas , Ratas Wistar , Resistencia Vascular/efectos de los fármacos , Función Ventricular Izquierda/efectos de los fármacosRESUMEN
BACKGROUND: The 2 major dietary sources of trans fatty acids (TFAs) are partially hydrogenated oils and ruminant-derived products. Epidemiologic data suggest that chronic consumption of industrial sources of TFAs could be damaging to insulin sensitivity, but intervention studies on this issue have remained inconclusive. OBJECTIVE: The trial was designed to compare the effects of dairy compared with industrial sources of TFAs on insulin sensitivity in overweight women. DESIGN: Sixty-three healthy women with abdominal obesity [waist circumference >88 cm and a body mass index (in kg/m(2)) >28] were recruited. After a run-in period, the volunteers were randomly assigned to consume 1 of 3 four-week diets: 60 g low-TFA lipids/d (0.54 g/d; n = 21), ruminant TFA-rich lipids (4.86 g/d; n = 21), or industrial TFA-rich lipids (5.58 g/d; n = 21). Changes in peripheral insulin sensitivity were assessed by using hyperinsulinemic-euglycemic clamps. RESULTS: After the intervention period, fasting glycemia and insulinemia and insulin sensitivity were not significantly modified in either group (P > 0.05). CONCLUSIONS: These data indicate that consumption of dairy- and industrial-source TFAs for 4 wk at nutritional levels do not impair peripheral insulin sensitivity in insulin-resistant women. Our study may not preassess the effects of TFAs in normal insulin-sensitive individuals. This trial was registered at ClinicalTrials.gov as NCT00617435.
Asunto(s)
Productos Lácteos , Resistencia a la Insulina/fisiología , Insulina/farmacología , Obesidad/sangre , Sobrepeso/fisiopatología , Ácidos Grasos trans/farmacología , Adolescente , Adulto , Animales , Glucemia/efectos de los fármacos , Glucemia/metabolismo , Composición Corporal , Índice de Masa Corporal , Grasas de la Dieta/farmacología , Método Doble Ciego , Femenino , Técnica de Clampeo de la Glucosa , Humanos , Hiperinsulinismo , Cooperación del Paciente , Fosfolípidos/sangre , Rumiantes , Circunferencia de la Cintura , Adulto JovenRESUMEN
Epidemiological studies suggest that chronic consumption of trans MUFA may alter muscle insulin sensitivity. The major sources of dietary trans MUFA (dairy fat vs. industrially hydrogenated oils) have different isomeric profiles and thus probably different metabolic consequences. These effects may involve alterations in muscle mitochondrial oxidative capacity, which may in turn promote insulin resistance if fatty acid oxidation is reduced. We report that in Wistar rats, an 8 week diet enriched (4% of energy intake) in either dairy, industrial, or control MUFA did not alter insulin and glucose responses to an intraperitoneal glucose tolerance test (1g/kg). In C2C12 myotubes, vaccenic and elaidic acids did not modify insulin sensitivity compared with oleic acid. Furthermore, the ex vivo total, mitochondrial and peroxisomal oxidation rates of [1-(14)C]oleic, vaccenic, and elaidic acids were similar in soleus and tibialis anterior rat muscle. Finally, an 8 week diet enriched in either dairy or industrial trans MUFA did not alter mitochondrial oxidative capacity in these two muscles compared with control MUFA but did induce a specific reduction in soleus mitochondrial ATP and superoxide anion production (P<0.01 vs. control). In conclusion, dietary trans MUFA of dairy or industrial origin have similar effects and do not impair muscle mitochondrial capacity and insulin sensitivity.
Asunto(s)
Grasas de la Dieta/farmacología , Industrias , Insulina/farmacología , Mitocondrias/efectos de los fármacos , Músculos/efectos de los fármacos , Aceites/farmacología , Ácidos Grasos trans/farmacología , Adenosina Trifosfato/biosíntesis , Alimentación Animal , Animales , Composición Corporal , Línea Celular , Grasas de la Dieta/metabolismo , Masculino , Ratones , Mitocondrias/metabolismo , Membranas Mitocondriales/metabolismo , Músculos/metabolismo , Aceites/metabolismo , Oxidación-Reducción , Ratas , Ratas Wistar , Superóxidos/metabolismo , Ácidos Grasos trans/metabolismoRESUMEN
Abdominal obesity increases the incidence of cardiac events but reduces mortality when one of these events occurs. The phenomenon called obesity paradox might be related to myocardial energetics. This study was aimed at determining whether long-term abdominal adiposity alters cardiac energy function. Two groups of male Wistar rats were fed a standard or a Western-type (WD) diet for 8 months. The ex vivo coronary reactivity and mechanical function as well as the mitochondrial oxidative phosphorylation (mOxPhos) and hydrogen peroxide release (mH2O2r) were determined. Abdominal adiposity was augmented by the WD. This was also the case for the coronary reactivity to acetylcholine, but the rate pressure product remained roughly stable despite a reduction of the left ventricle-developed pressure partly compensated by a slight increase in heart rate. The prolonged WD administration resulted in an improvement of mOxPhos, but the mH2O2r was exaggerated which was confirmed in the whole cell by a reduced aconitase to fumarase ratio. This did not modify the plasma oxidative stress due to an increased plasma antioxidant status. In conclusion, long-term WD administration improved the cardiac fitness and might predispose the organism to the obesity paradox. Conversely, the increased mitochondrial mH2O2r can precipitate the heart toward cardiomyopathy if the WD is maintained for a longer duration (AU)
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