MyD88 signaling in the CNS is required for development of fatty acid-induced leptin resistance and diet-induced obesity. Export

@article{citeulike:5937973, abstract = {Obesity-associated activation of inflammatory pathways represents a key step in the development of insulin resistance in peripheral organs, partially via activation of TLR4 signaling by fatty acids. Here, we demonstrate that palmitate acting in the central nervous system (CNS) inhibits leptin-induced anorexia and Stat3 activation. To determine the functional significance of TLR signaling in the CNS in the development of leptin resistance and diet-induced obesity in vivo, we have characterized mice deficient for the TLR adaptor molecule MyD88 in the CNS (MyD88(DeltaCNS)). Compared to control mice, MyD88(DeltaCNS) mice are protected from high-fat diet (HFD)-induced weight gain, from the development of HFD-induced leptin resistance, and from the induction of leptin resistance by acute central application of palmitate. Moreover, CNS-restricted MyD88 deletion protects from HFD- and icv palmitate-induced impairment of peripheral glucose metabolism. Thus, we define neuronal MyD88-dependent signaling as a key regulator of diet-induced leptin and insulin resistance in vivo.}, author = {Kleinridders, Andr\'{e} and Schenten, Dominik and K\"{o}nner, A. Christine and Belgardt, Bengt F. and Mauer, Jan and Okamura, Tomoo and Wunderlich, F. Thomas and Medzhitov, Ruslan and Br\"{u}ning, Jens C.}, citeulike-article-id = {5937973}, citeulike-linkout-0 = {http://dx.doi.org/10.1016/j.cmet.2009.08.013}, citeulike-linkout-1 = {http://linkinghub.elsevier.com/retrieve/pii/S1550413109002630}, citeulike-linkout-2 = {http://view.ncbi.nlm.nih.gov/pubmed/19808018}, citeulike-linkout-3 = {http://www.hubmed.org/display.cgi?uids=19808018}, day = {07}, doi = {10.1016/j.cmet.2009.08.013}, issn = {1932-7420}, journal = {Cell metabolism}, keywords = {hypothalamus, inflammation, insulin-resistance, myd88}, month = {October}, number = {4}, pages = {249--259}, posted-at = {2009-10-15 04:56:31}, priority = {2}, title = {MyD88 signaling in the CNS is required for development of fatty acid-induced leptin resistance and diet-induced obesity.}, url = {http://dx.doi.org/10.1016/j.cmet.2009.08.013}, volume = {10}, year = {2009} }

TY - JOUR ID - citeulike:5937973 L3 - citeulike-article-id:5937973 N2 - Obesity-associated activation of inflammatory pathways represents a key step in the development of insulin resistance in peripheral organs, partially via activation of TLR4 signaling by fatty acids. Here, we demonstrate that palmitate acting in the central nervous system (CNS) inhibits leptin-induced anorexia and Stat3 activation. To determine the functional significance of TLR signaling in the CNS in the development of leptin resistance and diet-induced obesity in vivo, we have characterized mice deficient for the TLR adaptor molecule MyD88 in the CNS (MyD88(DeltaCNS)). Compared to control mice, MyD88(DeltaCNS) mice are protected from high-fat diet (HFD)-induced weight gain, from the development of HFD-induced leptin resistance, and from the induction of leptin resistance by acute central application of palmitate. Moreover, CNS-restricted MyD88 deletion protects from HFD- and icv palmitate-induced impairment of peripheral glucose metabolism. Thus, we define neuronal MyD88-dependent signaling as a key regulator of diet-induced leptin and insulin resistance in vivo. IS - 4 JF - Cell metabolism SN - 1932-7420 EP - 259 TI - MyD88 signaling in the CNS is required for development of fatty acid-induced leptin resistance and diet-induced obesity. VL - 10 SP - 249 KW - hypothalamus KW - inflammation KW - insulin-resistance KW - myd88 AU - Kleinridders, André AU - Schenten, Dominik AU - Könner, Christine AU - Belgardt, Bengt AU - Mauer, Jan AU - Okamura, Tomoo AU - Wunderlich, Thomas AU - Medzhitov, Ruslan AU - Brüning, Jens PY - 2009/10/07/ UR - http://dx.doi.org/10.1016/j.cmet.2009.08.013 ER -