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TNF-alpha induces mitochondrial dysfunction in 3T3-L1 adipocytes.
Chen, Xiao-Hui; Zhao, Ya-Ping; Xue, Mei; Ji, Chen-Bo; Gao, Chun-Lin; Zhu, Jin-Gai; Qin, Da-Ni; Kou, Chun-Zhao; Qin, Xiao-Hong; Tong, Mei-Ling; Guo, Xi-Rong.
Afiliação
  • Chen XH; Department of Pediatrics, Nanjing Maternal and Child Health Hospital, Nanjing Medical University, Nanjing 210004, China.
Mol Cell Endocrinol ; 328(1-2): 63-9, 2010 Oct 26.
Article em En | MEDLINE | ID: mdl-20667497
ABSTRACT
TNF-alpha was the first proinflammatory cytokine identified linking obesity, insulin resistance and chronic inflammation. However, the mechanism of TNF-alpha in the etiology of insulin resistance is still far from clear. Because the mitochondria play an important role in energy metabolism, we investigated whether mitochondrial dysfunction is involved in pathogenesis of TNF-alpha-mediated insulin resistance. First, a fully differentiated insulin-resistant 3T3-L1 adipocyte model was established by incubating with 4 ng/ml TNF-alpha for 4 d, and then the mitochondrial morphology and functions were observed. TNF-alpha treatment induced pronounced morphological changes in the mitochondria, which became smaller and condensed, and some appeared hollow and absent of cristae. Mitochondrial dynamics changes were observed as increased mitofusion protein mfn1 and mitofission protein Drp1 levels compared with controls. No obvious effects on mitochondrial biogenesis were found. PGC-1alpha levels decreased, but no significant changes were found in mtTFA mRNA expression, NRF1mRNA expression and mitochondrial DNA (mtDNA). TNFalpha treatment also led to decreased mitochondrial membrane potential and reduced production of intracellular ATP, as well as accumulation of significant amounts of reactive oxygen species (ROS). Further research is required to determine if mitochondrial dysfunction is involved in the inflammatory mechanism of insulin resistance and may be a potential target for the treatment of insulin resistance.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Fator de Necrose Tumoral alfa / Adipócitos / Mitocôndrias Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Revista: Mol Cell Endocrinol Ano de publicação: 2010 Tipo de documento: Article País de afiliação: China

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Fator de Necrose Tumoral alfa / Adipócitos / Mitocôndrias Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Revista: Mol Cell Endocrinol Ano de publicação: 2010 Tipo de documento: Article País de afiliação: China