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Type: Artigo
Title: Saturated fatty acids produce an inflammatory response predominantly through the activation of TLR4 signaling in hypothalamus: implications for the pathogenesis of obesity
Author: Anhe, Gabriel
Amaral, Maria E.
Coope, Andressa
Tsukumo, Daniela M. L.
Degasperi, Giovanna
Milanski, Marciane
Cintra, Dennys E.
Morari, Joseane
Denis, Raphael
Oliveira, Helena C.
Takahashi, Hilton K.
Curi, Rui
Carvalheira, Jose B. C.
Velloso, Licio A.
Saad, Mario J.
Bordin, Silvana
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: Inflamação
Country: Estados Unidos
Editor: Society for Neuroscience
Citation: JOURNAL OF NEUROSCIENCE, v.29, n.2, p.359-370, 2009
Rights: fechado
Identifier DOI: 10.1523/JNEUROSCI.2760-08.2009
Date Issue: 2009
Appears in Collections:FCM - Artigos e Outros Documentos

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