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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

Increase in hypothalamic AMPK phosphorylation induced by prolonged exposure to LPS involves ghrelin and CB1R signaling

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Autor(es):
Rivas, Priscila M. S. ; Vechiato, Fernanda M. V. ; Borges, Beatriz C. ; Rorato, Rodrigo ; Antunes-Rodrigues, Jose ; Elias, Lucila L. K.
Número total de Autores: 6
Tipo de documento: Artigo Científico
Fonte: Hormones and Behavior; v. 93, p. 166-174, JUL 2017.
Citações Web of Science: 2
Resumo

Acute administration of lipopolysaccharide (LPS) from Gram-negative bacteria induces hypophagia. However, the repeated administration of LPS leads to desensitization of hypophagia, which is associated with increased hypothalamic p-AMPK expression. Because ghrelin and endocannabinoids modulate AMPK activity in the hypothalamus, we hypothesized that these neuromodulators play a role in the reversal of tolerance to hypophagia in rats under long-term exposure to LPS. Male Wistar rats were treated with single (1 LPS, 100 mu g/kg body weight, ip) or repeated injections of LPS over 6 days (6 LPS). Food intake was reduced in the 1 LPS, but not in the 6 LPS group. 6 LPS rats showed an increased serum concentration of acylated ghrelin and reduced ghrelin receptor mRNA expression in the hypothalamus. Ghrelin injection (40 mu g/kg body weight, ip) increased food intake, body weight gain, p-AMPK hypothalamic expression, neuropeptide Y (NPY) and Agouti related peptide (AgRP) mRNA expression in control animals (Saline). However, in 6 LPS rats, ghrelin did not alter these parameters. Central administration of a CB1R antagonist (AM251, 200 mu g/pl in 5 mu l/rat) induced hypophagia in 6 LPS animals, suggesting that the endocannabinoid system contributes to preserved food intake during LPS tolerance. In the presence of AM251, the ability of ghrelin to phosphorylate AMPK in the hypothalamus of 6 LPS group was restored, but not its orexigenic effect Our data highlight that the orexigenic effects of ghrelin require CB1R signaling downstream of AMPK activation. Moreover, CB1R-mediated pathways contribute to the absence of hypophagia during repeated exposure to endotoxin. (C) 2017 Elsevier Inc. All rights reserved. (AU)

Processo FAPESP: 12/18179-4 - Avaliação do efeito da exposição ao ácido graxo saturado e à dieta hiperlipídica na sinalização do receptor CB2 em células da microglia
Beneficiário:Rodrigo César Rorato
Linha de fomento: Bolsas no Brasil - Pós-Doutorado
Processo FAPESP: 13/03915-0 - Papel da via de sinalização da PI3K na resistência à leptina induzida por endotoxina
Beneficiário:Beatriz de Carvalho Borges Del Grande
Linha de fomento: Bolsas no Exterior - Estágio de Pesquisa - Pós-Doutorado
Processo FAPESP: 13/09799-1 - Regulação da homeostase energética e do balanço hidromineral: das células aos sistemas fisiológicos
Beneficiário:José Antunes Rodrigues
Linha de fomento: Auxílio à Pesquisa - Temático