High-fat diet inhibits PGC-1 alpha suppressive effect on NF kappa B signaling in hepatocytes

Autor(es)

Barroso, Wermerson Assuncao ^[1] ; Victorino, Vanessa Jacob ^[1] ; Jeremias, Isabela Casagrande ^[1] ; Petroni, Ricardo Costa ^[1] ; Kubo Ariga, Suely Kunimi ^[1] ; Salles, Thiago A. ^[2] ; Barbeiro, Denise Frediani ^[1] ; de Lima, Thais Martins ^[1] ; de Souza, Heraldo Possolo ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Sch Med, Dept Clin Med, Emergency Med Lab LIM51, Ave Dr Arnaldo 455, BR-01246903 Sao Paulo, SP - Brazil

^[2] Univ Sao Paulo, Heart Inst InCor, Sch Med, Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: EUROPEAN JOURNAL OF NUTRITION; v. 57, n. 5, p. 1891-1900, AUG 2018.
• Citações Web of Science: 6

Resumo

The peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1 alpha) regulates the expression of genes implicated in fatty acid oxidation and oxidative phosphorylation. Its role in liver steatosis is well established, since mice with liver-specific deletion of PGC-1 alpha exhibit lipid accumulation and high-fat diet reduces hepatic PGC-1 alpha expression in mice. In this study, we investigated the role of PGC-1 alpha in the inflammatory changes observed in steatohepatitis induced by high-fat diet. C57black/6 mice were fed a high-fat diet containing 30% fat for 10 weeks. After euthanasia, liver morphology was examined by HE staining and inflammation was determined by IL-6, TNF-alpha, and IL-1 beta quantification. Liver gene expression of PGC-1 isoforms was evaluated by real-time PCR and p65 NF kappa B nuclear translocation by Western blotting. HepG2 cells were treated with linoleic acid overload for 72 h to create an in vitro model of steatohepatitis. RNA interference (RNAi) was used to evaluate the involvement of PGC-1 alpha on inflammatory mediators' production by hepatocytes. The high-fat diet led to a state of nonalcoholic steatohepatitis, associated with increased deposits of intra-abdominal fat, hyperglycemia and hyperlipidemia. Mice liver also exhibited increased proinflammatory cytokines' levels, decreased PGC-1 alpha expression, and marked increase in p65 NF kappa B nuclear translocation. Linoleic acid treated cells also presented increased expression of proinflammatory cytokines and decreased PGC-1 alpha expression. The knockdown of PGC-1 alpha content caused an increase in IL-6 expression and release via enhanced I kappa B alpha phosphorylation and subsequent increase of p65 NF kappa B nuclear translocation. High-fat diet induces liver inflammation by inhibiting PGC-1 alpha expression and its suppressive effect in NF kappa B pathway. (AU)

• Processo FAPESP: 12/07957-6 - Os coativadores da transcrição gênica PGC-1 no processo inflamatório
• Beneficiário: Heraldo Possolo de Souza
• Modalidade de apoio: Auxílio à Pesquisa - Regular