Modulation of intestinal L-glutamate transport by luminal leptin

Leptin is secreted into the digestive tract and contributes to the absorption of dietary molecules by regulating transporters activity. Here, we studied the effect of luminal leptin on the intestinal transport of L-glutamate, an important component of human diet. We examined the effect of leptin on L-glutamate uptake in rat intestine in vitro measuring glutamate-induced short-circuit current (Isc) in Ussing chambers and L-[3H (U)]-glutamate uptake in jejunal everted rings. Glutamate-induced Isc was only observed in Na+-free conditions. This Isc was concentration (1–60 mmol L−1) and pH dependent. Luminal leptin increased glutamate Isc (∼100 %). Dose-response curve showed a biphasic pattern, with maximal stimulations observed at 10−13 and 10−10 mmol L−1, that were sensitive to leptin receptor antagonist. In everted rings, two glutamate transport mechanisms were distinguished: a Na+-dependent, H+-independent, that was inhibited by leptin (∼20 %), and a Na+-independent but H+-dependent, that was enhanced by leptin (∼20 %), in line with data obtained in Ussing chambers. Altogether, these data reveal original non-monotonic effect of luminal leptin in the intestine and demonstrate a new role for this hormone in the modulation of L-glutamate transport, showing that luminal active gut peptides can influence absorption of amino acids

Basal leptin regulates amino acid uptake in polarized Caco-2 cells

Leptin is secreted by gastric mucosa and is able to reach the intestinal lumen where its receptors are located in the apical membrane of the enterocytes. We have previously demonstrated that apical leptin inhibits sugar and amino acids uptake in vitro and glucose absorption in vivo. Since leptin receptors are also expressed in the basolateral membrane of the enterocytes, the aim of the present work was to investigate whether leptin acting from the basolateral side could also regulate amino acid uptake. Tritiated Gln and β-Ala were used to measure uptake into Caco-2 cells grown on filters, in the presence of basal leptin at short incubation times (5 and 30 min) and after 6 h of preincubation with the hormone. In order to compare apical and basal leptin effect, Gln and β-Ala uptake was measured in the presence of leptin acting from the apical membrane also in cells grown on filters. Basal leptin (8 mM) inhibited by ~15-30% the uptake of 0.1 mM Gln and 1 mM β-Ala quickly, after 5 min exposure, and the effect was maintained after long preincubation periods. Apical leptin had the same effect. Moreover, the inhibition was rapidly and completely reversed when leptin was removed from the apical or basolateral medium. These results extend our previous findings and contribute to the vision of leptin as an important hormonal signal for the regulation of intestinal absorption of nutrients

Mecanismos reparadores neuronales en la enfermedad de Alzheimer / Neuronal repair mechanisms in Alzheimer's disease

La enfermedad de Alzheimer (EA) es el tipo de demencia más frecuente y afecta a unos 15 millones de personas en el mundo. A pesar de su alta incidencia, aún no disponemos de un método de diagnóstico claro, eficaz y excluyente para esta afección. En la actualidad éste se realiza con precaución tras la observación de una serie de síntomas, entre los que se encuentran la pérdida de memoria, alteraciones en el lenguaje, etc. En cuanto al tratamiento de la EA, en los últimos años están adquiriendo importancia otros abordajes de tipo no farmacológicos como es la rehabilitación neuronal. Este tratamiento es un proceso terapéutico altamente individualizado, específicamente desarrollado para resolver las necesidades del paciente y está basado en la plasticidad del cerebro. De la misma manera, se conoce que la nutrición desempeña un papel muy relevante en el desarrollo de numerosas afecciones, incluidas las enfermedades neurodegenerativas. Son muchas las evidencias que sustentan la idea de la participación del estrés oxidativo en el desarrollo de la EA y en los procesos apoptóticos que se deriven de ella. En este sentido, el consumo de antioxidantes, en la dieta o a través de suplementos dietéticos, parece ser neuroprotector y puede mitigar el declive cognitivo. Ambas terapias (farmacológica y no farmacológica) comparten los mismos objetivos: retrasar el deterioro, recuperar funciones perdidas o mantenerlas conservadas y mejorar la calidad de vida (AU)

Alzheimer's disease (AD) is the most common type of dementia, affecting 15 million persons worldwide. Despite the high incidence of this disease, a clear and effective diagnostic method specific to AD is lacking. Currently, diagnosis of AD is made with caution, after observation of a series of symptoms that include memory loss and speech alterations, among others. In the last few years, non-pharmacological approaches, such as neuronal rehabilitation, have become more important in the treatment of AD. This form of treatment is highly individualized, specifically developed to resolve the needs of the patient and are based on cerebral plasticity. Nutrition plays a major role in the development of numerous diseases included under the heading of neurodegenerative disorders. A large body of evidence supports the role of oxidative stress in the development of AD and in apoptotic processes involved in this disease. Antioxidant intake, whether through the diet or in the form of supplements, seems to confer neuroprotection and could mitigate against cognitive decline. Both forms of treatment (pharmacological and non-pharmacological) share a common goal: to delay impairment, recover lost function or conserve existing function and improve quality of life (AU)