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Loss of transglutaminase 2 sensitizes for diet-induced obesity-related inflammation and insulin resistance due to enhanced macrophage c-Src signaling.
Sághy, Tibor; Köröskényi, Krisztina; Hegedus, Krisztina; Antal, Miklós; Bankó, Csaba; Bacsó, Zsolt; Papp, Attila; Stienstra, Rinke; Szondy, Zsuzsa.
Afiliação
  • Sághy T; Dental Biochemistry, Faculty of Dentistry, University of Debrecen, Debrecen, Hungary.
  • Köröskényi K; Dental Biochemistry, Faculty of Dentistry, University of Debrecen, Debrecen, Hungary.
  • Hegedus K; Department of Biochemistry and Molecular Biology, Faculty of General Medicine, University of Debrecen, Debrecen, Hungary.
  • Antal M; Department of Anatomy, Histology and Embryology, Faculty of General Medicine, University of Debrecen, Debrecen, Hungary.
  • Bankó C; Department of Anatomy, Histology and Embryology, Faculty of General Medicine, University of Debrecen, Debrecen, Hungary.
  • Bacsó Z; Department of Biophysics and Cell Biology, Faculty of General Medicine, University of Debrecen, Debrecen, Hungary.
  • Papp A; Department of Biophysics and Cell Biology, Faculty of General Medicine, University of Debrecen, Debrecen, Hungary.
  • Stienstra R; Department of Biochemistry and Molecular Biology, Faculty of General Medicine, University of Debrecen, Debrecen, Hungary.
  • Szondy Z; Division of Human Nutrition and Health, Wageningen University, Wageningen, The Netherlands.
Cell Death Dis ; 10(6): 439, 2019 06 05.
Article em En | MEDLINE | ID: mdl-31165747
ABSTRACT
Transglutaminase 2 (TG2) is a multifunctional protein that promotes clearance of apoptotic cells (efferocytosis) acting as integrin ß3 coreceptor. Accumulating evidence indicates that defective efferocytosis contributes to the development of chronic inflammatory diseases. Obesity is characterized by the accumulation of dead adipocytes and inflammatory macrophages in the adipose tissue leading to obesity-related metabolic syndrome. Here, we report that loss of TG2 from bone marrow-derived cells sensitizes for high fat diet (HFD)-induced pathologies. We find that metabolically activated TG2 null macrophages express more phospho-Src and integrin ß3, unexpectedly clear dying adipocytes more efficiently via lysosomal exocytosis, but produce more pro-inflammatory cytokines than the wild type ones. Anti-inflammatory treatment with an LXR agonist reverts the HFD-induced phenotype in mice lacking TG2 in bone marrow-derived cells with less hepatic steatosis than in wild type mice proving enhanced lipid clearance. Thus it is interesting to speculate whether LXR agonist treatment together with enhancing lysosomal exocytosis could be a beneficial therapeutic strategy in obesity.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Resistência à Insulina / Transglutaminases / Proteínas de Ligação ao GTP / Inflamação / Macrófagos / Obesidade Tipo de estudo: Etiology_studies Limite: Animals Idioma: En Revista: Cell Death Dis Ano de publicação: 2019 Tipo de documento: Article País de afiliação: Hungria

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Resistência à Insulina / Transglutaminases / Proteínas de Ligação ao GTP / Inflamação / Macrófagos / Obesidade Tipo de estudo: Etiology_studies Limite: Animals Idioma: En Revista: Cell Death Dis Ano de publicação: 2019 Tipo de documento: Article País de afiliação: Hungria