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Adipocyte mTORC1 deficiency promotes adipose tissue inflammation and NLRP3 inflammasome activation via oxidative stress and de novo ceramide synthesis.
Chimin, Patricia; Andrade, Maynara L; Belchior, Thiago; Paschoal, Vivian A; Magdalon, Juliana; Yamashita, Alex S; Castro, Érique; Castoldi, Angela; Chaves-Filho, Adriano B; Yoshinaga, Marcos Y; Miyamoto, Sayuri; Câmara, Niels O; Festuccia, William T.
Afiliación
  • Chimin P; Departments of Physiology and Biophysics University of Sao Paulo, Sao Paulo, Brazil 05508000; Department of Physical Education, Physical Education and Sports Center, Londrina State University, Parana, Brazil 86051-990.
  • Andrade ML; Departments of Physiology and Biophysics University of Sao Paulo, Sao Paulo, Brazil 05508000.
  • Belchior T; Departments of Physiology and Biophysics University of Sao Paulo, Sao Paulo, Brazil 05508000.
  • Paschoal VA; Departments of Physiology and Biophysics University of Sao Paulo, Sao Paulo, Brazil 05508000.
  • Magdalon J; Departments of Physiology and Biophysics University of Sao Paulo, Sao Paulo, Brazil 05508000.
  • Yamashita AS; Departments of Physiology and Biophysics University of Sao Paulo, Sao Paulo, Brazil 05508000.
  • Castro É; Departments of Physiology and Biophysics University of Sao Paulo, Sao Paulo, Brazil 05508000.
  • Castoldi A; Immunology, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, Brazil 05508000.
  • Chaves-Filho AB; Department of Biochemistry, Institute of Chemistry, University of Sao Paulo, Sao Paulo, Brazil 05508000.
  • Yoshinaga MY; Department of Biochemistry, Institute of Chemistry, University of Sao Paulo, Sao Paulo, Brazil 05508000.
  • Miyamoto S; Department of Biochemistry, Institute of Chemistry, University of Sao Paulo, Sao Paulo, Brazil 05508000.
  • Câmara NO; Immunology, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, Brazil 05508000.
  • Festuccia WT; Departments of Physiology and Biophysics University of Sao Paulo, Sao Paulo, Brazil 05508000. Electronic address: william.festuccia@gmail.com.
J Lipid Res ; 58(9): 1797-1807, 2017 09.
Article en En | MEDLINE | ID: mdl-28679588
Mechanistic target of rapamycin complex (mTORC)1 activity is increased in adipose tissue of obese insulin-resistant mice, but its role in the regulation of tissue inflammation is unknown. Herein, we investigated the effects of adipocyte mTORC1 deficiency on adipose tissue inflammation and glucose homeostasis. For this, mice with adipocyte raptor deletion and controls fed a chow or a high-fat diet were evaluated for body mass, adiposity, glucose homeostasis, and adipose tissue inflammation. Despite reducing adiposity, adipocyte mTORC1 deficiency promoted hepatic steatosis, insulin resistance, and adipose tissue inflammation (increased infiltration of macrophages, neutrophils, and B lymphocytes; crown-like structure density; TNF-α, interleukin (IL)-6, and monocyte chemoattractant protein 1 expression; IL-1ß protein content; lipid peroxidation; and de novo ceramide synthesis). The anti-oxidant, N-acetylcysteine, partially attenuated, whereas treatment with de novo ceramide synthesis inhibitor, myriocin, completely blocked adipose tissue inflammation and nucleotide oligomerization domain-like receptor pyrin domain-containing 3 (NLRP3)-inflammasome activation, but not hepatic steatosis and insulin resistance induced by adipocyte raptor deletion. Rosiglitazone treatment, however, completely abrogated insulin resistance induced by adipocyte raptor deletion. In conclusion, adipocyte mTORC1 deficiency induces adipose tissue inflammation and NLRP3-inflammasome activation by promoting oxidative stress and de novo ceramide synthesis. Such adipose tissue inflammation, however, is not an underlying cause of the insulin resistance displayed by these mice.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Ceramidas / Tejido Adiposo / Adipocitos / Estrés Oxidativo / Inflamasomas / Proteína con Dominio Pirina 3 de la Familia NLR / Diana Mecanicista del Complejo 1 de la Rapamicina Límite: Animals Idioma: En Revista: J Lipid Res Año: 2017 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Ceramidas / Tejido Adiposo / Adipocitos / Estrés Oxidativo / Inflamasomas / Proteína con Dominio Pirina 3 de la Familia NLR / Diana Mecanicista del Complejo 1 de la Rapamicina Límite: Animals Idioma: En Revista: J Lipid Res Año: 2017 Tipo del documento: Article Pais de publicación: Estados Unidos