Please use this identifier to cite or link to this item: http://repositorio.unicamp.br/jspui/handle/REPOSIP/918
Type: Artigo de periódico
Title: Saturated Fatty Acids Produce an Inflammatory Response Predominantly through the Activation of TLR4 Signaling in Hypothalamus: Implications for the Pathogenesis of Obesity
Author: MILANSKI, Marciane
DEGASPERI, Giovanna
COOPE, Andressa
MORARI, Joseane
DENIS, Raphael
CINTRA, Dennys E.
TSUKUMO, Daniela M. L.
ANHE, Gabriel
AMARAL, Maria E.
TAKAHASHI, Hilton K.
CURI, Rui
OLIVEIRA, Helena C.
CARVALHEIRA, Jose B. C.
BORDIN, Silvana
SAAD, Mario J.
VELLOSO, Licio A.
Abstract: In animal models of diet-induced obesity, the activation of an inflammatory response in the hypothalamus produces molecular and functional resistance to the anorexigenic hormones insulin and leptin. The primary events triggered by dietary fats that ultimately lead to hypothalamic cytokine expression and inflammatory signaling are unknown. Here, we test the hypothesis that dietary fats act through the activation of toll-like receptors 2/4 and endoplasmic reticulum stress to induce cytokine expression in the hypothalamus of rodents. According to our results, long-chain saturated fatty acids activate predominantly toll-like receptor 4 signaling, which determines not only the induction of local cytokine expression but also promotes endoplasmic reticulum stress. Rats fed on a monounsaturated fat-rich diet do not develop hypothalamic leptin resistance, whereas toll-like receptor 4 loss-of-function mutation and immunopharmacological inhibition of toll-like receptor 4 protects mice from diet-induced obesity. Thus, toll-like receptor 4 acts as a predominant molecular target for saturated fatty acids in the hypothalamus, triggering the intracellular signaling network that induces an inflammatory response, and determines the resistance to anorexigenic signals.
Subject: obesity
inflammation
hypothalamus
cytokine
nutrition
feeding
Country: Estados Unidos
Editor: SOC NEUROSCIENCE
Citation: JOURNAL OF NEUROSCIENCE, v.29, n.2, p.359-370, 2009
Rights: fechado
Identifier DOI: 10.1523/JNEUROSCI.2760-08.2009
Address: http://dx.doi.org/10.1523/JNEUROSCI.2760-08.2009
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Date Issue: 2009
Appears in Collections:FCM - Artigos e Materiais de Revistas Científicas

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