Saturated fatty acids produce an inflammatory response predominantly through the activation of TLR4 signaling in hypothalamus: implications for the pathogenesis of obesity. Export

@article{citeulike:4163605, 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.}, author = {Milanski, M. and Degasperi, G. and Coope, A. and Morari, J. and Denis, R. and Cintra, D. E. and Tsukumo, D. M. and Anhe, G. and Amaral, M. E. and Takahashi, H. K. and Curi, R. and Oliveira, H. C. and Carvalheira, J. B. and Bordin, S. and Saad, M. J. and Velloso, L. A.}, citeulike-article-id = {4163605}, citeulike-linkout-0 = {http://dx.doi.org/10.1523/JNEUROSCI.2760-08.2009}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/19144836}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=19144836}, day = {14}, doi = {10.1523/JNEUROSCI.2760-08.2009}, issn = {1529-2401}, journal = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, keywords = {hypothalamus, inflammation, toll-like-receptor}, month = {January}, number = {2}, pages = {359--370}, posted-at = {2009-03-11 02:18:01}, priority = {2}, title = {Saturated fatty acids produce an inflammatory response predominantly through the activation of TLR4 signaling in hypothalamus: implications for the pathogenesis of obesity.}, url = {http://dx.doi.org/10.1523/JNEUROSCI.2760-08.2009}, volume = {29}, year = {2009} }

TY - JOUR ID - citeulike:4163605 L3 - citeulike-article-id:4163605 N2 - 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. IS - 2 JF - The Journal of neuroscience : the official journal of the Society for Neuroscience SN - 1529-2401 EP - 370 TI - Saturated fatty acids produce an inflammatory response predominantly through the activation of TLR4 signaling in hypothalamus: implications for the pathogenesis of obesity. VL - 29 SP - 359 KW - hypothalamus KW - inflammation KW - toll-like-receptor AU - Milanski, M AU - Degasperi, G AU - Coope, A AU - Morari, J AU - Denis, R AU - Cintra, DE AU - Tsukumo, DM AU - Anhe, G AU - Amaral, ME AU - Takahashi, HK AU - Curi, R AU - Oliveira, HC AU - Carvalheira, JB AU - Bordin, S AU - Saad, MJ AU - Velloso, LA PY - 2009/01/14/ UR - http://dx.doi.org/10.1523/JNEUROSCI.2760-08.2009 ER -