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Type: Artigo de periódico
Title: Inhibition Of Hypothalamic Foxo1 Expression Reduced Food Intake In Diet-induced Obesity Rats.
Author: Ropelle, Eduardo R
Pauli, José R
Prada, Patrícia
Cintra, Dennys E
Rocha, Guilherme Z
Moraes, Juliana C
Frederico, Marisa J S
da Luz, Gabrielle
Pinho, Ricardo A
Carvalheira, José B C
Velloso, Licio A
Saad, Mario A
De Souza, Cláudio T
Abstract: Insulin signalling in the hypothalamus plays a role in maintaining body weight. The forkhead transcription factor Foxo1 is an important mediator of insulin signalling in the hypothalamus. Foxo1 stimulates the transcription of the orexigenic neuropeptide Y and Agouti-related protein through the phosphatidylinositol-3-kinase/Akt signalling pathway, but the role of hypothalamic Foxo1 in insulin resistance and obesity remains unclear. Here, we identify that a high-fat diet impaired insulin-induced hypothalamic Foxo1 phosphorylation and degradation, increasing the nuclear Foxo1 activity and hyperphagic response in rats. Thus, we investigated the effects of the intracerebroventricular (i.c.v.) microinfusion of Foxo1-antisense oligonucleotide (Foxo1-ASO) and evaluated the food consumption and weight gain in normal and diet-induced obese (DIO) rats. Three days of Foxo1-ASO microinfusion reduced the hypothalamic Foxo1 expression by about 85%. i.c.v. infusion of Foxo1-ASO reduced the cumulative food intake (21%), body weight change (28%), epididymal fat pad weight (22%) and fasting serum insulin levels (19%) and increased the insulin sensitivity (34%) in DIO but not in control animals. Collectively, these data showed that the Foxo1-ASO treatment blocked the orexigenic effects of Foxo1 and prevented the hyperphagic response in obese rats. Thus, pharmacological manipulation of Foxo1 may be used to prevent or treat obesity.
Subject: Adipose Tissue, White
Blood Glucose
Body Weight
Cell Nucleus
Energy Intake
Forkhead Transcription Factors
Gene Expression
Insulin Receptor Substrate Proteins
Nerve Tissue Proteins
Oligonucleotides, Antisense
Proto-oncogene Proteins C-akt
Rats, Wistar
Receptor, Insulin
P300-cbp Transcription Factors
Citation: The Journal Of Physiology. v. 587, n. Pt 10, p. 2341-51, 2009-May.
Rights: fechado
Identifier DOI: 10.1113/jphysiol.2009.170050
Date Issue: 2009
Appears in Collections:Unicamp - Artigos e Outros Documentos

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