RESUMEN
High-fat diets alter gut barrier integrity, leading to endotoxemia by impacting epithelial functions and inducing endoplasmic reticulum (ER) stress in intestinal secretory goblet cells. Indeed, ER stress, which is an important contributor to many chronic diseases such as obesity and obesity-related disorders, leads to altered synthesis and secretion of mucins that form the protective mucus barrier. In the present study, we investigated the relative contribution of omega-3 polyunsaturated fatty acid (PUFAs)-modified microbiota to alleviating alterations in intestinal mucus layer thickness and preserving gut barrier integrity. Male fat-1 transgenic mice (exhibiting endogenous omega-3 PUFAs tissue enrichment) and wild-type (WT) littermates were fed either an obesogenic high-fat diet (HFD) or a control diet. Unlike WT mice, HFD-fed fat-1 mice were protected against mucus layer alterations as well as an ER stress-mediated decrease in mucin expression. Moreover, cecal microbiota transferred from fat-1 to WT mice prevented changes in the colonic mucus layer mainly through colonic ER stress downregulation. These findings highlight a novel feature of the preventive effects of omega-3 fatty acids against intestinal permeability in obesity-related conditions.
Asunto(s)
Colon , Dieta Alta en Grasa , Estrés del Retículo Endoplásmico , Ácidos Grasos Omega-3 , Microbioma Gastrointestinal , Mucosa Intestinal , Ratones Transgénicos , Animales , Dieta Alta en Grasa/efectos adversos , Ratones , Masculino , Ácidos Grasos Omega-3/metabolismo , Colon/microbiología , Colon/metabolismo , Mucosa Intestinal/metabolismo , Mucosa Intestinal/microbiología , Obesidad/metabolismo , Obesidad/microbiología , Moco/metabolismo , Ratones Endogámicos C57BL , Mucinas/metabolismo , Células Caliciformes/metabolismo , Trasplante de Microbiota FecalRESUMEN
BACKGROUND/OBJECTIVES: Adipose tissue macrophages (ATM) are key actors in the pathophysiology of obesity-related diseases. They have a unique intermediate M2-M1 phenotype which has been linked to endoplasmic reticulum (ER) stress. We previously reported that human M2 macrophages treated with the ER stress inducer thapsigargin switched to a pro-inflammatory phenotype that depended on the stress protein GRP94. In these conditions, GRP94 promoted cathepsin L secretion and was co-secreted with complement C3. As cathepsin L and complement C3 have been reported to play a role in the pathophysiology of obesity, in this work we studied the involvement of GRP94 in the pro-inflammatory phenotype of ATM. METHODS: GRP94, cathepsin L and C3 expression were analyzed in CD206 + ATM from mice, WT or obesity-resistant transgenic fat-1, fed a high-fat diet (HFD) or a standard diet. GRP94 colocalization with cathepsin L and C3 and its effects were analyzed in human primary macrophages using thapsigargin as a control to induce ER stress and palmitic acid (PA) as a driver of metabolic activation. RESULTS: In WT, but not in fat-1 mice, fed a HFD, we observed an increase in crown-like structures consisting of CD206 + pSTAT1+ macrophages showing high expression of GRP94 that colocalized with cathepsin L and C3. In vitro experiments showed that PA favored a M2-M1 switch depending on GRP94. This switch was prevented by omega-3 fatty acids. PA-induced GRP94-cathepsin L colocalization and a decrease in cathepsin L enzymatic activity within the cells (while the enzymatic activity in the extracellular medium was increased). These effects were prevented by the GRP94 inhibitor PU-WS13. CONCLUSIONS: GRP94 is overexpressed in macrophages both in in vivo and in vitro conditions of obesity-associated inflammation and is involved in changing their profile towards a more pro-inflammatory profile. It colocalizes with complement C3 and cathepsin L and modulates cathepsin L activity.
Asunto(s)
Catepsina L , Estrés del Retículo Endoplásmico , Inflamación , Macrófagos , Obesidad , Animales , Ratones , Estrés del Retículo Endoplásmico/fisiología , Obesidad/metabolismo , Macrófagos/metabolismo , Catepsina L/metabolismo , Inflamación/metabolismo , Humanos , Dieta Alta en Grasa , Modelos Animales de Enfermedad , Tejido Adiposo/metabolismo , Masculino , Ratones Endogámicos C57BL , Glicoproteínas de Membrana/metabolismo , Ratones TransgénicosRESUMEN
Mitochondria have emerged as key actors of innate and adaptive immunity. Mitophagy has a pivotal role in cell homeostasis, but its contribution to macrophage functions and host defense remains to be delineated. Here, we showed that lipopolysaccharide (LPS) in combination with IFN-γ inhibited PINK1-dependent mitophagy in macrophages through a STAT1-dependent activation of the inflammatory caspases 1 and 11. In addition, we demonstrated that the inhibition of mitophagy triggered classical macrophage activation in a mitochondrial ROS-dependent manner. In a murine model of polymicrobial infection (cecal ligature and puncture), adoptive transfer of Pink1-deficient bone marrow or pharmacological inhibition of mitophagy promoted macrophage activation, which favored bactericidal clearance and led to a better survival rate. Reciprocally, mitochondrial uncouplers that promote mitophagy reversed LPS/IFN-γ-mediated activation of macrophages and led to immunoparalysis with impaired bacterial clearance and lowered survival. In critically ill patients, we showed that mitophagy was inhibited in blood monocytes of patients with sepsis as compared with nonseptic patients. Overall, this work demonstrates that the inhibition of mitophagy is a physiological mechanism that contributes to the activation of myeloid cells and improves the outcome of sepsis.
Asunto(s)
Bacterias/inmunología , Activación de Macrófagos , Macrófagos Peritoneales/inmunología , Mitofagia/inmunología , Sepsis/inmunología , Animales , Femenino , Humanos , Interferón gamma/inmunología , Lipopolisacáridos/inmunología , Macrófagos Peritoneales/microbiología , Macrófagos Peritoneales/patología , Masculino , Ratones , Proteínas Quinasas/inmunología , Células RAW 264.7 , Sepsis/microbiología , Sepsis/patologíaRESUMEN
Diets high in saturated fatty acids (FA) represent a risk factor for the development of obesity and associated metabolic disorders, partly through their impact on the epithelial cell barrier integrity. We hypothesized that unsaturated FA could alleviate saturated FA-induced endoplasmic reticulum (ER) stress occurring in intestinal secretory goblet cells, and consequently the reduced synthesis and secretion of mucins that form the protective mucus barrier. To investigate this hypothesis, we treated well-differentiated human colonic LS174T goblet cells with palmitic acid (PAL)-the most commonly used inducer of lipotoxicity in in vitro systems-or n-9, n-6, or n-3 unsaturated fatty acids alone or in co-treatment with PAL, and measured the impact of such treatments on ER stress and Muc2 production. Our results showed that only eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids protect goblet cells against ER stress-mediated altered Muc2 secretion induced by PAL, whereas neither linolenic acid nor n-9 and n-6 FA are able to provide such protection. We conclude that EPA and DHA could represent potential therapeutic nutrients against the detrimental lipotoxicity of saturated fatty acids, associated with type 2 diabetes and obesity or inflammatory bowel disease. These in vitro data remain to be explored in vivo in a context of dietary obesity.
Asunto(s)
Ácidos Docosahexaenoicos/farmacología , Ácido Eicosapentaenoico/farmacología , Estrés del Retículo Endoplásmico/efectos de los fármacos , Células Caliciformes/efectos de los fármacos , Mucina 2/metabolismo , Ácido Palmítico/toxicidad , Línea Celular , Citoprotección , Células Caliciformes/metabolismo , Células Caliciformes/patología , Humanos , Factor 4 Similar a Kruppel , Factores de Transcripción de Tipo Kruppel/metabolismo , Vías SecretorasRESUMEN
Obesity is now widely recognized to be associated with low-grade systemic inflammation. It has been shown that high-fat feeding modulates gut microbiota which strongly increased intestinal permeability leading to lipopolysaccharide absorption causing metabolic endotoxemia that triggers inflammation and metabolic disorders. N-3 polyunsaturated fatty acids (PUFAs) have been shown associated with anti-obesity properties, but results still remain heterogeneous and very few studies underlined the metabolic pathways involved. Thus, the use of Fat-1 transgenic mice allows to better understanding whether endogenous n-3 PUFAs enrichment contributes to obesity and associated metabolic disorders prevention. It specially evidence that such effects occur through modulations of gut microbiota and intestinal permeability. Then, by remodeling gut microbiota, endogenous n-3 PUFAs improve HF/HS-diet induced features of the metabolic syndrome which in turn affects host metabolism. Thus, increasing anti-obesogenic microbial species in the gut microbiota population (i.e Akkermansia) by appropriate n-3 PUFAs may represent a promising strategy to control or prevent metabolic diseases.
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Disbiosis , Ácidos Grasos Omega-3/uso terapéutico , Microbioma Gastrointestinal/efectos de los fármacos , Enfermedades Metabólicas , Obesidad , Animales , Disbiosis/metabolismo , Disbiosis/microbiología , Disbiosis/prevención & control , Humanos , Enfermedades Metabólicas/metabolismo , Enfermedades Metabólicas/microbiología , Enfermedades Metabólicas/prevención & control , Ratones , Obesidad/metabolismo , Obesidad/microbiología , Obesidad/prevención & controlRESUMEN
Altering the gut microbiome may be beneficial to the host and recently arose as a promising strategy to manage obesity. Here, we investigated the relative contribution of ω3 polyunsaturated fatty acid (PUFA)-mediated alterations in the microbiota to metabolic parameter changes in mice. Four groups were compared: male fat-1 transgenic mice (with constitutive production of ω3 PUFAs) and male wild-type (WT) littermates fed an obesogenic (high fat/high sucrose [HFHS]) or a control diet. Unlike WT mice, HFHS-fed fat-1 mice were protected against obesity, glucose intolerance, and hepatic steatosis. Unlike WT mice, fat-1 mice maintained a normal barrier function, resulting in a significantly lower metabolic endotoxemia. The fat-1 mice displayed greater phylogenic diversity in the cecum, and fecal microbiota transplantation from fat-1 to WT mice was able to reverse weight gain and to normalize glucose tolerance and intestinal permeability. We concluded that the ω3 PUFA-mediated alteration of gut microbiota contributed to the prevention of metabolic syndrome in fat-1 mice. It occurred independently of changes in the PUFA content of host tissues and may represent a promising strategy to prevent metabolic disease and preserve a lean phenotype.
Asunto(s)
Ácidos Grasos Omega-3/metabolismo , Trasplante de Microbiota Fecal , Microbioma Gastrointestinal , Intolerancia a la Glucosa/prevención & control , Resistencia a la Insulina , Enfermedad del Hígado Graso no Alcohólico/prevención & control , Obesidad/prevención & control , Animales , Cadherinas/genética , Cadherinas/metabolismo , Dieta de Carga de Carbohidratos/efectos adversos , Dieta Alta en Grasa/efectos adversos , Sacarosa en la Dieta/efectos adversos , Disbiosis/microbiología , Disbiosis/fisiopatología , Disbiosis/terapia , Endotoxemia/etiología , Endotoxemia/prevención & control , Trasplante de Microbiota Fecal/efectos adversos , Intolerancia a la Glucosa/microbiología , Intolerancia a la Glucosa/patología , Intolerancia a la Glucosa/fisiopatología , Mucosa Intestinal/metabolismo , Mucosa Intestinal/microbiología , Mucosa Intestinal/patología , Mucosa Intestinal/fisiopatología , Intestinos/microbiología , Intestinos/patología , Intestinos/fisiopatología , Hígado/metabolismo , Hígado/patología , Masculino , Ratones Transgénicos , Músculo Esquelético/metabolismo , Enfermedad del Hígado Graso no Alcohólico/microbiología , Enfermedad del Hígado Graso no Alcohólico/patología , Enfermedad del Hígado Graso no Alcohólico/fisiopatología , Obesidad/microbiología , Obesidad/patología , Obesidad/fisiopatología , Permeabilidad , FilogeniaRESUMEN
Pyrethroid insecticides are extensively used in agriculture and in household activities. During pregnancy, they might affect maternal metabolic status and there after fetal development. In this work, we studied metabolic and redox effects of low dose alpha-cypermethrin exposure in pregnant rats and their offspring. The diet containing alpha cypermethrin at 0.02mg/kg/day was consumed during the entire gestation. Plasma biochemical parameters as well as liver lipid and oxidative stress markers were determined. Our results showed that alpha-cypermethrin induced an increase in body weight and in plasma glucose and lipid levels, as well as in plasma aspartate aminotransferase, alanine aminotransferase and alkaline phosphatase activities in pregnant rats and their newborns. Pregnant rats showed cellular oxidative stress and altered oxidant-antioxidant status when treated by the insecticide and these disturbances were also seen in their newborns. In conclusion, low dose alpha-cypermethrin exposure induced several metabolic and redox alterations leading to maternal physiological impairments and to fetal metabolic changes. Alpha-cypermethrin should be used with caution especially during pregnancy.
Asunto(s)
Insecticidas/toxicidad , Enfermedades Metabólicas/inducido químicamente , Estrés Oxidativo/efectos de los fármacos , Efectos Tardíos de la Exposición Prenatal , Piretrinas/toxicidad , Alanina Transaminasa/sangre , Animales , Animales Recién Nacidos , Aspartato Aminotransferasas/sangre , Glucemia/análisis , Peso Corporal/efectos de los fármacos , Femenino , Glutatión/metabolismo , Lípidos/sangre , Hígado/efectos de los fármacos , Hígado/metabolismo , Malondialdehído/metabolismo , Intercambio Materno-Fetal , Enfermedades Metabólicas/sangre , Enfermedades Metabólicas/metabolismo , Oxidación-Reducción , Embarazo , Ratas , Ratas WistarRESUMEN
The aim of this investigation was to determine the in vitro effects of vitamin C and E, n-3 and n-6 PUFA and n-9 MUFA on placental cell proliferation and function in type 1 diabetes. Placenta tissues were collected from 30 control healthy and 30 type 1 diabetic women at delivery. Placental cells were isolated and were cultured in RPMI medium supplemented with vitamin C (50 µM), vitamin E (50 µM), n-3 PUFA (100 µM), n-6 PUFA (100 µM) or n-9 MUFA (100 µM). Cell proliferation, cell glucose uptake and intracellular oxidative status were investigated. Our results showed that basal placental cell proliferation, glucose uptake, malondialdehyde (MDA) and carbonyl proteins were higher while intracellular reduced glutathione (GSH) levels and catalase activities were lower in placentas from diabetic women as compared to controls. Vitamins C and E induced a modulation of placental cell proliferation and glucose consumption without affecting intracellular redox status in both diabetic and control groups. N-3 and n-6 PUFA diminished placental cell proliferation and enhanced intracellular oxidative stress while n-9 MUFA had no effects in the two groups. Co-administration of n-3 or n-6 PUFA and vitamin C or E were capable of reversing back the PUFA-decreased cell proliferation and normalizing placental cell function and redox status especially in diabetes. In conclusion, PUFA and antioxidant vitamin combinations may be beneficial in improving placenta function and in reducing placental oxidative stress in type 1 diabetic pregnancy.
Asunto(s)
Antioxidantes/farmacología , Diabetes Mellitus Tipo 1/metabolismo , Estrés Oxidativo/efectos de los fármacos , Placenta/efectos de los fármacos , Embarazo en Diabéticas/metabolismo , Adulto , Ácido Ascórbico/farmacología , Catalasa/metabolismo , Proliferación Celular/efectos de los fármacos , Ácidos Grasos Monoinsaturados/farmacología , Ácidos Grasos Omega-3/farmacología , Ácidos Grasos Omega-6/farmacología , Femenino , Humanos , Malondialdehído/metabolismo , Oxidación-Reducción , Placenta/metabolismo , Embarazo , Superóxido Dismutasa/metabolismo , Vitamina E/farmacología , Adulto JovenRESUMEN
The aim of this work was to investigate inflammatory, oxidative, and thrombotic parameters as biomarkers in farmers exposed to pesticides. Fifty farmers using chemical pesticides and 60 unexposed control men participated in this study. The Mediterranean diet compliance, the duration of pesticide use, and personal protection for pesticides handling were recorded using self-administered questionnaires. Serum biochemical parameters, oxidant/antioxidant, inflammatory, and thrombosis markers were determined. Our findings showed oxidative stress reflected by an increase in malondialdehyde, carbonyl proteins and superoxide anion levels and a decrease in vitamins C and E, glutathione, catalase, and superoxide dismutase activities in farmers. Serum C-reactive protein, prothrombin, and fibrinogen levels were enhanced in these farmers. In conclusion, inflammation, oxidative stress, and metabolic perturbations reflected the possibility of the effects of pesticides to farmers.
Asunto(s)
Biomarcadores/sangre , Agricultores , Hemostáticos/sangre , Inflamación/sangre , Exposición Profesional/análisis , Plaguicidas/envenenamiento , Adulto , Ácido Ascórbico/sangre , Proteína C-Reactiva/metabolismo , Catalasa/sangre , Fibrinógeno/metabolismo , Glutatión/sangre , Humanos , Inflamación/etiología , Modelos Logísticos , Masculino , Malondialdehído/sangre , Persona de Mediana Edad , Exposición Profesional/efectos adversos , Oxidación-Reducción/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Carbonilación Proteica , Protrombina/metabolismo , Superóxido Dismutasa/sangre , Superóxidos/sangre , Encuestas y Cuestionarios , Vitamina E/sangreRESUMEN
OBJECTIVE: The present study was undertaken to evaluate the variation of the oxidative/nitrosative stress status in a population of subjects; with acute coronary syndrome (ACS), and examine its possible implication in plaque rupture which is the main mechanism in the pathophysiology of ACS. PATIENTS AND METHODS: We made this study on 50 men with ACS and 50 age and sex matched healthy controls. Nitrosative/oxidative stress markers including; nitric oxide, superoxide anion levels, superoxide dismutase (SOD) activity and peroxynitrite levels were evaluated in blood samples of patients and controls. RESULTS: Compared with healthy subjects, coronary patients had significantly higher nitric oxide, peroxynitrite and superoxide anion concentrations in both plasma and erythrocytes associated to significant decrease of SOD activity. Erythrocytes peroxynitrite concentration was negatively correlated with the antioxidant enzyme activity (SOD). CONCLUSION: Our results show a significant accumulation of both intracellular and plasma pro-oxidants with a concomitant decrease in the SOD scavenging activity in ACS patients. Both seem to be associated with plaque rupture and ischemia observed in ACS.
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Síndrome Coronario Agudo/enzimología , Síndrome Coronario Agudo/metabolismo , Óxido Nítrico/metabolismo , Ácido Peroxinitroso/metabolismo , Superóxido Dismutasa/metabolismo , Estudios de Casos y Controles , Femenino , Humanos , Masculino , Persona de Mediana Edad , Óxido Nítrico/sangre , Estrés Oxidativo/fisiología , Ácido Peroxinitroso/sangre , Superóxido Dismutasa/sangreRESUMEN
Because linseed oil may influence maternal and fetal metabolisms, we investigated its role in the modulation of lipid metabolism in cafeteria diet-induced obese rats and their offspring. Female Wistar rats were fed control or cafeteria food, which were either supplemented or not supplemented with linseed oil (5%) for 1 month before and during gestation. At parturition, serum and tissue lipids and enzyme activities were analyzed. Cafeteria diet induced adverse metabolic alterations in both mothers and offspring. Linseed oil improved metabolic status. In conclusion, linseed oil displayed health benefits by modulating tissue enzyme activities in both obese mothers and their newborns.
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Dieta/efectos adversos , Aceite de Linaza/metabolismo , Metabolismo de los Lípidos/efectos de los fármacos , Obesidad/tratamiento farmacológico , Efectos Tardíos de la Exposición Prenatal/tratamiento farmacológico , Alimentación Animal/análisis , Animales , Suplementos Dietéticos/análisis , Femenino , Aceite de Linaza/administración & dosificación , Fenómenos Fisiologicos Nutricionales Maternos/efectos de los fármacos , Obesidad/etiología , Obesidad/metabolismo , Embarazo , Efectos Tardíos de la Exposición Prenatal/etiología , Efectos Tardíos de la Exposición Prenatal/metabolismo , Distribución Aleatoria , Ratas , Ratas WistarRESUMEN
OBJECTIVE: To investigate the oxidative profile and thrombotic markers in obese and hypertensive mothers. METHODS: Thirty obese, 28 hypertensive and 34 healthy control mothers were recruited from Tlemcen Hospital, Algeria. Plasma vitamin C, nitric oxide, superoxide anion, erythrocyte glutathione, malondialdehyde, carbonyl proteins and erythrocyte antioxidant enzyme activities and coagulation markers [protein C, protein S, fibrinogen, prothrombin, antithrombin, activated partial thromboplastin time (APTT), lupus anticoagulants (LACs)] were measured. Changes in plasma urea, creatinine, uric acid, glucose and lipid levels were also determined. RESULTS: Plasma glucose concentrations were high in obese mothers, and plasma urea, uric acid and creatinine levels were increased in hypertensive compared with healthy mothers. Obese and hypertensive mothers had low vitamin C and glutathione values, catalase and superoxide dismutase activities, and high triglyceride, superoxide anion, malondialdehyde and carbonyl protein levels compared with control mothers. Plasma nitric oxide levels were enhanced in obese mothers but reduced in hypertensive mothers. Fibrinogen and prothrombin levels were significantly enhanced in obese and hypertensive mothers. Protein C, protein S, antithrombin and APTT values were significantly higher in hypertensive mothers. Only hypertensive mothers were positive for LACs. CONCLUSION: Obese and hypertensive mothers presented oxidative stress and a pro-thrombotic state. Their oxidative and hemostasis profile should be carefully considered and appropriate management organized.
Asunto(s)
Hipertensión/metabolismo , Obesidad/sangre , Trombosis/metabolismo , Adulto , Estudios de Casos y Controles , Femenino , Humanos , Estrés Oxidativo , EmbarazoRESUMEN
OBJECTIVE: Liver X receptors (LXRs) modulate cholesterol and fatty acid homeostasis as well as inflammation. This study aims to decipher the role of LXRs in the regulation of polyunsaturated fatty acid (PUFA) synthesis in macrophages in the context of atherosclerosis. APPROACH AND RESULTS: Transcriptomic analysis in human monocytes and macrophages was used to identify putative LXR target genes among enzymes involved in PUFA biosynthesis. In parallel, the consequences of LXR activation or LXR invalidation on PUFA synthesis and distribution were determined. Finally, we investigated the impact of LXR activation on PUFA metabolism in vivo in apolipoprotein E-deficient mice. mRNA levels of acyl-CoA synthase long-chain family member 3, fatty acid desaturases 1 and 2, and fatty acid elongase 5 were significantly increased in human macrophages after LXR agonist treatment, involving both direct and sterol responsive element binding protein-1-dependent mechanisms. Subsequently, pharmacological LXR agonist increased long chain PUFA synthesis and enhanced arachidonic acid content in the phospholipids of human macrophages. Increased fatty acid desaturases 1 and 2 and acyl-CoA synthase long-chain family member 3 mRNA levels as well as increased arachidonic acid to linoleic acid and docosahexaenoic acid to eicosapentaenoic acid ratios were also found in atheroma plaque and peritoneal foam cells from LXR agonist-treated mice. By contrast, murine LXR-deficient macrophages displayed reduced expression of fatty acid elongase 5, acyl-CoA synthase long-chain family member 3 and fatty acid desaturases 1, as well as decreased cellular levels of docosahexaenoic acid and arachidonic acid. CONCLUSIONS: Our results indicate that LXR activation triggers PUFA synthesis in macrophages, which results in significant alterations in the macrophage lipid composition. Moreover, we demonstrate here that LXR agonist treatment modulates PUFA metabolism in atherosclerotic arteries.
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Aterosclerosis/metabolismo , Ácidos Grasos Insaturados/biosíntesis , Macrófagos/metabolismo , Receptores Nucleares Huérfanos/metabolismo , Animales , Ácido Araquidónico/metabolismo , Arterias/metabolismo , Células Espumosas/metabolismo , Humanos , Receptores X del Hígado , Ratones , Receptores Nucleares Huérfanos/agonistas , Proteína 1 de Unión a los Elementos Reguladores de Esteroles/metabolismoRESUMEN
BACKGROUND: The aim of this investigation was to determine the in vitro effects of linseed, olive and Nigel oils on T cell proliferation and function in gestational diabetes. METHODS: Blood samples were collected from 40 control healthy and 32 gestational diabetic mothers and their newborns. Peripheral blood lymphocytes were isolated using a density gradient of Ficoll. T cell proliferation, interleukin-2 and -4 (IL-2, IL-4) secretion, fatty acid composition and intracellular oxidative status were investigated. RESULTS: Mitogen (Concanavalin A) stimulated lymphocyte proliferation, IL-2 secretion, intracellular reduced glutathione levels, superoxide dismutase (SOD) and catalase activities were lower while intracellular malondialdehyde (MDA) and carbonyl proteins were higher in diabetic mothers and in their newborns as compared to their respective controls. Linseed oil induced a reduction in T-lymphocyte proliferation and IL-2 production, and alpha linolenic acid membrane enrichment in both diabetic and control groups. In the presence of Nigel oil, T-lymphocyte proliferation and IL-2 secretion, phospholipid linoleic and oleic acids were enhanced. Olive oil had no effect on lymphocyte proliferation in all groups. Linseed, olive and Nigel oils induced an increase in T cell levels of reduced glutathione levels and in activities of catalase and SOD with a concomitant decrease in MDA and carbonyl protein contents. CONCLUSION: Linseed, olive and Nigel oils had beneficial effects on T cell functions in gestational diabetes.
Asunto(s)
Diabetes Gestacional/inmunología , Ácidos Grasos/administración & dosificación , Aceites de Plantas/administración & dosificación , Linfocitos T/inmunología , Adulto , Femenino , Humanos , Técnicas In Vitro , Recién Nacido , EmbarazoRESUMEN
The effects of calcium antagonists (amlodipine) and angiotensin II receptor antagonists (telmisartan) on lipid profile and oxidative markers were investigated in Algerian hypertensive patients. At the beginning and after 1 year of antihypertensive therapy, blood samples are collected for determination of biochemical parameters (glucose, cholesterol, triglycerides, urea, creatinine) and oxidative markers (malondialdehyde, carbonyl proteins, nitric oxide, superoxide anion, vitamin C, glutathione, catalase, superoxide dismutase). The results of this study indicate that telmisartan and amlodipine are effective antihypertensive agents in the treatment of hypertension because a significant reduction in systolic and diastolic blood pressure was observed in all hypertensive patients after 1 year of treatment. Our results show also that telmisartan and amlodipine treatments counteracted hypertension-dependent lipid abnormalities and oxidative stress. Telmisartan treatment appears to be more efficient than amlodipine treatment. In addition, telmisartan, which reversed all lipid and redox changes associated with hypertension, should be prescribed, especially in hypertensive patients with hypertriglyceridemia and with severe oxidative stress.
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Amlodipino/uso terapéutico , Antagonistas de Receptores de Angiotensina/uso terapéutico , Bencimidazoles/uso terapéutico , Benzoatos/uso terapéutico , Bloqueadores de los Canales de Calcio/uso terapéutico , Hipertensión/tratamiento farmacológico , Estrés Oxidativo , Argelia , Femenino , Humanos , Hipertensión/metabolismo , Masculino , Persona de Mediana Edad , TelmisartánRESUMEN
Overexpression of the tyrosine kinase receptor ErbB2/HER2/Neu, occurs in 25%-30% of invasive breast cancer (BC) with poor patient prognosis. Even if numerous studies have shown prevention of breast cancer by n-3 fatty acid intake, the experimental conditions under which n-3 fatty acids exert their protective effect have been variable from study to study, preventing unifying conclusions. Due to confounding factors, inconsistencies still remain regarding protective effects of n-3 polyunsaturated fatty acids (PUFA) on BC. When animals are fed with dietary supplementation in n-3 fatty acids (the traditional approach to modify tissue content and decrease the n-6/n-3 ratio) complex dietary interactions can occur among dietary lipids (antioxidants, vitamins ) that can modulate the activity of n-3 fatty acids. So, what are the specific roles of these n-3 PUFA in reducing breast cancer risk and particularly preventing HER2-positive breast cancer? In this review, we discuss crucial points that may account for discrepancies of results and provide a highly effective genetic approach that can eliminate confounding factors of diet for evaluating the molecular mechanisms of n-3 PUFA in HER2 signaling pathway regulation. The fat-1 transgenic mouse model is capable of converting n-6 to n-3 fatty acids leading to an increase in n-3 fatty acid content with a balanced n-6/n-3 fatty acid ratio in all tissues. The fat-1 mouse model allows well-controlled studies in HER2-positive breast cancer prevention to be performed, without the conflict of potential confounding factors of diet.
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Neoplasias de la Mama/metabolismo , Ácidos Grasos Omega-3/fisiología , Receptor ErbB-2/metabolismo , Animales , Anticarcinógenos/administración & dosificación , Neoplasias de la Mama/prevención & control , Proteínas de Caenorhabditis elegans/genética , Suplementos Dietéticos , Modelos Animales de Enfermedad , Ácido Graso Desaturasas/genética , Ácidos Grasos Omega-3/administración & dosificación , Femenino , Humanos , Ratones , Ratones TransgénicosRESUMEN
Overexpression of the tyrosine kinase receptor, ErbB2/HER2/Neu, occurs in 25-30% of invasive breast cancer (BC) with poor patient prognosis. Due to confounding factors, inconsistencies still remain regarding the protective effects of n-3 polyunsaturated fatty acids (PUFAs) on BC. We therefore evaluated whether fat-1 transgenic mice, endogenously synthesizing n-3 PUFAs from n-6 PUFAs, were protected against BC development, and we then aimed to study in vivo a mechanism potentially involved in such protection. E0771 BC cells were implanted into fat-1 and wild-type (WT) mice. After tumorigenesis examination, we analyzed the expression of proteins involved in the HER2 signaling pathway and lipidomic analyses were performed in tumor tissues and plasma. Our results showed that tumors totally disappeared by day 15 in fat-1 mice but continued to grow in WT mice. This prevention can be related in part to significant repression of the HER2/ß-catenin signaling pathway and formation of significant levels of n-3 PUFA-derived bioactive mediators (particularly 15-hydroxyeicosapentaenoic acid, 17-hydroxydocosahexaenoic acid, and prostaglandin E3) in the tumors of fat-1 mice compared with WT mice. All together these data demonstrate an anti-BC effect of n-3 PUFAs through, at least in part, HER2 signaling pathway downregulation, and highlight the importance of gene-diet interactions in BC.