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000136511 0247_ $$2doi$$a10.1096/fj.11-191023
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000136511 041__ $$aEnglish
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000136511 1001_ $$0P:(DE-HGF)0$$aSartorius, Tina$$b0
000136511 245__ $$aToll-like receptors 2 and 4 impair insulin-mediated brain activity by interleukin-6 and osteopontin and alter sleep architecture.
000136511 260__ $$aBethesda, Md.$$bFASEB$$c2012
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000136511 520__ $$aImpaired insulin action in the brain represents an early step in the progression toward type 2 diabetes, and elevated levels of saturated free fatty acids are known to impair insulin action in prediabetic subjects. One potential mediator that links fatty acids to inflammation and insulin resistance is the Toll-like receptor (TLR) family. Therefore, C3H/HeJ/TLR2-KO (TLR2/4-deficient) mice were fed a high-fat diet (HFD), and insulin action in the brain as well as cortical and locomotor activity was analyzed by using telemetric implants. TLR2/4-deficient mice were protected from HFD-induced glucose intolerance and insulin resistance in the brain and displayed an improvement in cortical and locomotor activity that was not observed in C3H/HeJ mice. Sleep recordings revealed a 42% increase in rapid eye movement sleep in the deficient mice during daytime, and these mice spent 41% more time awake during the night period. Treatment of control mice with a neutralizing IL-6 antibody improved insulin action in the brain as well as cortical activity and diminished osteopontin protein to levels of the TLR2/4-deficient mice. Together, our data suggest that the lack of functional TLR2/4 protects mice from a fat-mediated impairment in insulin action, brain activity, locomotion, and sleep architecture by an IL-6/osteopontin-dependent mechanism.
000136511 536__ $$0G:(DE-HGF)POF3-345$$a345 - Population Studies and Genetics (POF3-345)$$cPOF3-345$$fPOF III$$x0
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000136511 650_7 $$2NLM Chemicals$$aInsulin
000136511 650_7 $$2NLM Chemicals$$aInterleukin-6
000136511 650_7 $$2NLM Chemicals$$aTlr2 protein, mouse
000136511 650_7 $$2NLM Chemicals$$aTlr4 protein, mouse
000136511 650_7 $$2NLM Chemicals$$aToll-Like Receptor 2
000136511 650_7 $$2NLM Chemicals$$aToll-Like Receptor 4
000136511 650_7 $$0106441-73-0$$2NLM Chemicals$$aOsteopontin
000136511 650_7 $$0EC 2.7.11.1$$2NLM Chemicals$$aProto-Oncogene Proteins c-akt
000136511 650_2 $$2MeSH$$aAnimals
000136511 650_2 $$2MeSH$$aAstrocytes: metabolism
000136511 650_2 $$2MeSH$$aBrain: physiology
000136511 650_2 $$2MeSH$$aCells, Cultured
000136511 650_2 $$2MeSH$$aElectroencephalography
000136511 650_2 $$2MeSH$$aGlucose Tolerance Test
000136511 650_2 $$2MeSH$$aInsulin: physiology
000136511 650_2 $$2MeSH$$aInsulin Resistance
000136511 650_2 $$2MeSH$$aInterleukin-6: immunology
000136511 650_2 $$2MeSH$$aInterleukin-6: physiology
000136511 650_2 $$2MeSH$$aLocomotion
000136511 650_2 $$2MeSH$$aMice
000136511 650_2 $$2MeSH$$aMice, Inbred C3H
000136511 650_2 $$2MeSH$$aMice, Knockout
000136511 650_2 $$2MeSH$$aOsteopontin: physiology
000136511 650_2 $$2MeSH$$aPhosphorylation
000136511 650_2 $$2MeSH$$aProto-Oncogene Proteins c-akt: metabolism
000136511 650_2 $$2MeSH$$aReal-Time Polymerase Chain Reaction
000136511 650_2 $$2MeSH$$aSleep
000136511 650_2 $$2MeSH$$aToll-Like Receptor 2: genetics
000136511 650_2 $$2MeSH$$aToll-Like Receptor 2: physiology
000136511 650_2 $$2MeSH$$aToll-Like Receptor 4: genetics
000136511 650_2 $$2MeSH$$aToll-Like Receptor 4: physiology
000136511 7001_ $$0P:(DE-HGF)0$$aLutz, Stefan Z$$b1
000136511 7001_ $$0P:(DE-HGF)0$$aHoene, Miriam$$b2
000136511 7001_ $$0P:(DE-2719)9000332$$aWaak, Jens$$b3$$udzne
000136511 7001_ $$0P:(DE-HGF)0$$aPeter, Andreas$$b4
000136511 7001_ $$0P:(DE-HGF)0$$aWeigert, Cora$$b5
000136511 7001_ $$0P:(DE-HGF)0$$aRammensee, Hans-Georg$$b6
000136511 7001_ $$0P:(DE-2719)2810803$$aKahle, Philipp J$$b7$$udzne
000136511 7001_ $$0P:(DE-HGF)0$$aHäring, Hans-Ulrich$$b8$$eCorresponding author
000136511 7001_ $$0P:(DE-HGF)0$$aHennige, Anita M$$b9
000136511 77318 $$2Crossref$$3journal-article$$a10.1096/fj.11-191023$$b : Wiley, 2012-01-25$$n5$$p1799-1809$$tThe FASEB Journal$$v26$$x0892-6638$$y2012
000136511 773__ $$0PERI:(DE-600)1468876-1$$a10.1096/fj.11-191023$$gVol. 26, no. 5, p. 1799 - 1809$$n5$$p1799-1809$$q26:5<1799 - 1809$$tThe FASEB journal$$v26$$x0892-6638$$y2012
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000136511 9141_ $$y2012
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