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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

Novel role of TLR4 in NAFLD development: Modulation of metabolic enzymes expression

Texto completo
Ferreira, Darkiane Fernandes [1] ; Fiamoncini, Jarlei [2] ; Prist, Iryna Hirata [1] ; Ariga, Suely Kubo [1] ; de Souza, Heraldo Possolo [1] ; de Lima, Thais Martins [1]
Número total de Autores: 6
Afiliação do(s) autor(es):
[1] Univ Sao Paulo, Sch Med, Dept Emergency Med, Sao Paulo - Brazil
[2] Tech Univ Munich, Biochem Unit, ZIEL Res Ctr Nutr & Food Sci, Freising Weihenstephan - Germany
Número total de Afiliações: 2
Tipo de documento: Artigo Científico
Citações Web of Science: 9

The rise in the prevalence of obesity and metabolic syndrome turned NAFLD as the most common cause of chronic liver diseases worldwide. Although the role of toll like receptors, especially TLR4, as activators of inflammatory pathways in liver diseases is well established, our goal was to investigate if TLR4 activation could modulate metabolic lipid pathways and alter the onset of NAFLD. We used LDL receptor-deficient mice (LDLrKO) fed with an atherogenic diet as a model. The role of TLR4 activation was evaluated by crossing LDLrKO mice with the TLR4 knockout mice. Animals were fed for 12 weeks with high-fat high-cholesterol diet (HFD) containing 18% saturated fat and 1.25% cholesterol. TLR4/LDLr KO mice presented lower triacylglyceride (TAG) plasma levels when compared to LDLrKO, despite the type of diet ingested. HFD induced TAG and cholesterol accumulation in the liver of all mice genotypes studied, but TLR4/LDLr KO presented lower TAG accumulation than LDLrKO mice. Gene expression of TAG synthesis enzymes (ApoB100, MTTP, GPAT1 and GPAT4) was not differentially altered in TLR4/LDLr KO and LDLrKO mice. On the other hand, TLR4 deficiency enhanced the expression of several enzymes involved in the oxidation of fatty acids, as follows: ACOX, CPT-1, MTPa, MTBb, PBE and 3-ketoacyl-CoA thiolase. Acyl-camitine plasma profile showed an increase in C0 and C2 concentration in TLR4/LDLr KO group, corroborating the hypothesis of increased fat oxidation. Our results indicate that TLR4 may have an important role in the onset of steatosis, once its depletion enhances fatty acid oxidation in the liver of mice, preventing triglyceride accumulation. (C) 2015 Elsevier B.V. All rights reserved. (AU)

Processo FAPESP: 09/01990-9 - Receptores nucleares e co-ativadores da transcrição gênica em doenças inflamatórias
Beneficiário:Heraldo Possolo de Souza
Linha de fomento: Auxílio à Pesquisa - Regular
Processo FAPESP: 09/07946-1 - Ativação de macrófagos por ácidos graxos: envolvimento na síndrome metabólica
Beneficiário:Thais Martins de Lima Salgado
Linha de fomento: Auxílio à Pesquisa - Regular