RESUMEN
Chronic disorders, such as obesity, diabetes, inflammation, non-alcoholic fatty liver disease and atherosclerosis, are related to alterations in lipid and glucose metabolism, in which peroxisome proliferator-activated receptors (PPAR)α, PPARß/δ and PPARγ are involved. These receptors form a subgroup of ligand-activated transcription factors that belong to the nuclear hormone receptor family. This review discusses a selection of novel PPAR functions identified during the last few years. The PPARs regulate processes that are essential for the maintenance of pregnancy and embryonic development. Newly found hepatic functions of PPARα are the mediation of female-specific gene repression and the protection of the liver from oestrogen induced toxicity. PPARα also controls lipid catabolism and is the target of hypolipidaemic drugs, whereas PPARγ controls adipocyte differentiation and regulates lipid storage; it is the target for the insulin sensitising thiazolidinediones used to treat type 2 diabetes. Activation of PPARß/δ increases lipid catabolism in skeletal muscle, the heart and adipose tissue. In addition, PPARß/δ ligands prevent weight gain and suppress macrophage derived inflammation. In fact, therapeutic benefits of PPAR ligands have been confirmed in inflammatory and autoimmune diseases, such as encephalomyelitis and inflammatory bowel disease. Furthermore, PPARs promote skin wound repair. PPARα favours skin healing during the inflammatory phase that follows injury, whilst PPARß/δ enhances keratinocyte survival and migration. Due to their collective functions in skin, PPARs represent a major research target for our understanding of many skin diseases. Taken altogether, these functions suggest that PPARs serve as physiological sensors in different stress situations and remain valuable targets for innovative therapies.
Asunto(s)
Inflamación/genética , Inflamación/fisiopatología , Síndrome Metabólico/genética , Síndrome Metabólico/fisiopatología , Receptores Activados del Proliferador del Peroxisoma/genética , Receptores Activados del Proliferador del Peroxisoma/fisiología , Animales , Enfermedades Autoinmunes/genética , Enfermedades Autoinmunes/fisiopatología , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/fisiopatología , Desarrollo Embrionario/genética , Desarrollo Embrionario/fisiología , Femenino , Regulación de la Expresión Génica/genética , Regulación de la Expresión Génica/fisiología , Humanos , Hiperlipidemias/genética , Hiperlipidemias/fisiopatología , Hígado/fisiopatología , Embarazo , Mantenimiento del Embarazo/genética , Mantenimiento del Embarazo/fisiología , Proteínas Represoras/genética , Proteínas Represoras/fisiología , Caracteres Sexuales , Enfermedades de la Piel/genética , Enfermedades de la Piel/fisiopatología , Cicatrización de Heridas/genética , Cicatrización de Heridas/fisiologíaRESUMEN
CONTEXT/OBJECTIVE: Not much is known about the implication of adipokines and different cytokines in gestational diabetes mellitus (GDM) and macrosomia. The purpose of this study was to assess the profile of these hormones and cytokines in macrosomic babies, born to gestational diabetic women. DESIGN/SUBJECTS: A total of 59 women (age, 19-42 yr) suffering from GDM with their macrosomic babies (4.35 +/- 0.06 kg) and 60 healthy age-matched pregnant women and their newborns (3.22 +/- 0.08 kg) were selected. METHODS: Serum adipokines (adiponectin and leptin) were quantified using an obesity-related multiple ELISA microarray kit. The concentrations of serum cytokines were determined by ELISA. RESULTS: Serum adiponectin levels were decreased, whereas the concentrations of leptin, inflammatory cytokines, such as IL-6 and TNF-alpha, were significantly increased in gestational diabetic mothers compared with control women. The levels of these adipocytokines were diminished in macrosomic babies in comparison with their age-matched control newborns. Serum concentrations of T helper type 1 (Th1) cytokines (IL-2 and interferon-gamma) were decreased, whereas IL-10 levels were significantly enhanced in gestational diabetic mothers compared with control women. Macrosomic children exhibited high levels of Th1 cytokines and low levels of IL-10 compared with control infants. Serum IL-4 levels were not altered between gestational diabetic mothers and control mothers or the macrosomic babies and newborn control babies. CONCLUSIONS: GDM is linked to the down-regulation of adiponectin along with Th1 cytokines and up-regulation of leptin and inflammatory cytokines. Macrosomia was associated with the up-regulation of Th1 cytokines and the down-regulation of the obesity-related agents (IL-6 and TNF-alpha, leptin, and adiponectin).
Asunto(s)
Citocinas/sangre , Diabetes Gestacional/inmunología , Macrosomía Fetal/inmunología , Leptina/sangre , Adiponectina/sangre , Adulto , Glucemia/análisis , Femenino , Humanos , Recién Nacido , Insulina/sangre , Interferón gamma/sangre , Interleucina-2/sangre , Interleucina-4/sangre , Interleucina-6/sangre , Lípidos/sangre , Masculino , Embarazo , Factor de Necrosis Tumoral alfa/análisisRESUMEN
OBJECTIVE: We investigated the role of dietary n-3 polyunsaturated fatty acids (n-3 PUFA) in the modulation of total antioxidant status in streptozotocin (STZ)-induced diabetic rats and their macrosomic offspring. DESIGN: Female wistar rats, fed on control diet or n-3 PUFA diet, were rendered diabetic by administration of five mild doses of STZ on day 5 and were killed on days 12 and 21 of gestation. The macrosomic (MAC) pups were killed at the age of 60 and 90 days. MEASUREMENTS: Lipid peroxidation was measured as the concentrations of plasma thiobarbituric acid reactive substances (TBARS), and the total antioxidant status was determined by measuring (i) plasma oxygen radical absorbance capacity (ORAC), (ii) plasma vitamin A, E and C concentrations, and (iii) antioxidant enzymes activities in erythrocytes. The plasma lipid concentrations and fatty acid composition were also determined. RESULTS: Diabetes increased plasma triglyceride and cholesterol concentrations, whereas macrosomia was associated with enhanced plasma cholesterol and triglyceride levels, which diminished by feeding n-3 PUFA diet. N-3 PUFA diet also reduced increased plasma TBARS and corrected the decreased ORAC values in diabetic rats and their macrosomic offspring. EPAX diet increased the diminished vitamin A levels in diabetic mothers and vitamin C concentrations in macrosomic pups. Also, this diet improved the decreased erythrocyte superoxide dismutase and glutathione peroxidase activities in diabetic and macrosomic animals. CONCLUSION: Diabetes and macrosomia were associated with altered lipid metabolism, antioxidant enzyme activities and vitamin concentrations. N-3 PUFA diet improved hyperlipidemia and restored antioxidant status in diabetic dams and MAC offspring.
Asunto(s)
Antioxidantes/metabolismo , Diabetes Mellitus/tratamiento farmacológico , Ácidos Grasos Omega-3/administración & dosificación , Embarazo en Diabéticas/tratamiento farmacológico , Animales , Animales Recién Nacidos , Ácido Ascórbico/sangre , Biomarcadores/sangre , Diabetes Mellitus/embriología , Diabetes Mellitus/metabolismo , Diabetes Mellitus Experimental/tratamiento farmacológico , Diabetes Mellitus Experimental/embriología , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/embriología , Diabetes Mellitus Tipo 2/metabolismo , Eritrocitos/enzimología , Ácidos Grasos/sangre , Femenino , Macrosomía Fetal/metabolismo , Depuradores de Radicales Libres/metabolismo , Glutatión Peroxidasa/sangre , Peroxidación de Lípido , Lípidos/sangre , Embarazo , Embarazo en Diabéticas/metabolismo , Ratas , Ratas Wistar , Superóxido Dismutasa/sangre , Sustancias Reactivas al Ácido Tiobarbitúrico/análisis , Vitamina A/sangre , Vitamina E/sangreRESUMEN
In the present study, we investigated the antioxidant status in diabetes mellitus, related or not to alcohol consumption. A total of 38 type 1, 48 type 2 and 42 alcohol-related diabetic patients were selected. Total antioxidant status was assessed through the oxygen radical absorbance capacity of the plasma and the determination of enzymatic and non-enzymatic antioxidant molecules. Serum triglycerides, total cholesterol and HDL-cholesterol concentrations were determined and the lipid peroxydation was evaluated by measuring thiobarbituric acid reactive substances (TBARS) assay. Plasma total antioxidant capacity was more decreased in alcohol-related diabetes than that in type 1 and type 2 diabetes, regardless of the complications (retinopathy and renal failure). Plasma vitamin E concentrations were significantly decreased whereas those of vitamin C increased in all of the diabetic patients compared to the controls, irrespective to the complications. In addition, superoxide dismutase and glutathione peroxidase activities were reduced in all the patients (type 1, type 2 and alcohol-related), irrespective to the complications. Glutathione reductase activity was diminished in type 1 and alcohol-related, but not in type 2, diabetic patients. Glutathione (GSH) concentrations significantly decreased in all diabetic patients with a significant decrease in alcohol-related diabetic patients. Excessive alcohol consumption appears as an oxidative aggravating factor in diabetes mellitus. Besides, alcohol-related diabetes highly resembles to type 1 diabetes as far as the antioxidant parameters are concerned.