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Hepatic acetyl CoA links adipose tissue inflammation to hepatic insulin resistance and type 2 diabetes.
Perry, Rachel J; Camporez, João-Paulo G; Kursawe, Romy; Titchenell, Paul M; Zhang, Dongyan; Perry, Curtis J; Jurczak, Michael J; Abudukadier, Abulizi; Han, Myoung Sook; Zhang, Xian-Man; Ruan, Hai-Bin; Yang, Xiaoyong; Caprio, Sonia; Kaech, Susan M; Sul, Hei Sook; Birnbaum, Morris J; Davis, Roger J; Cline, Gary W; Petersen, Kitt Falk; Shulman, Gerald I.
Afiliação
  • Perry RJ; Howard Hughes Medical Institute, Yale University, New Haven, CT 06519, USA; Department of Internal Medicine, Yale University, New Haven, CT 06520, USA; Department of Cellular and Molecular Physiology, Yale University, New Haven, CT 06520, USA.
  • Camporez JG; Department of Internal Medicine, Yale University, New Haven, CT 06520, USA.
  • Kursawe R; Department of Internal Medicine, Yale University, New Haven, CT 06520, USA.
  • Titchenell PM; The Institute for Diabetes, Obesity and Metabolism, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
  • Zhang D; Howard Hughes Medical Institute, Yale University, New Haven, CT 06519, USA.
  • Perry CJ; Department of Immunobiology, Yale University, New Haven, CT 06520, USA.
  • Jurczak MJ; Department of Internal Medicine, Yale University, New Haven, CT 06520, USA.
  • Abudukadier A; Department of Internal Medicine, Yale University, New Haven, CT 06520, USA.
  • Han MS; Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA.
  • Zhang XM; Howard Hughes Medical Institute, Yale University, New Haven, CT 06519, USA.
  • Ruan HB; Department of Comparative Medicine, Yale University, New Haven, CT 06520, USA.
  • Yang X; Department of Cellular and Molecular Physiology, Yale University, New Haven, CT 06520, USA; Department of Comparative Medicine, Yale University, New Haven, CT 06520, USA.
  • Caprio S; Department of Pediatrics, Yale University, New Haven, CT 06520, USA.
  • Kaech SM; Department of Immunobiology, Yale University, New Haven, CT 06520, USA.
  • Sul HS; Department of Nutritional Sciences and Toxicology, University of California, Berkeley, Berkeley, CA 94720, USA.
  • Birnbaum MJ; The Institute for Diabetes, Obesity and Metabolism, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
  • Davis RJ; Howard Hughes Medical Institute, Yale University, New Haven, CT 06519, USA; Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA.
  • Cline GW; Department of Internal Medicine, Yale University, New Haven, CT 06520, USA.
  • Petersen KF; Department of Internal Medicine, Yale University, New Haven, CT 06520, USA.
  • Shulman GI; Howard Hughes Medical Institute, Yale University, New Haven, CT 06519, USA; Department of Internal Medicine, Yale University, New Haven, CT 06520, USA; Department of Cellular and Molecular Physiology, Yale University, New Haven, CT 06520, USA. Electronic address: gerald.shulman@yale.edu.
Cell ; 160(4): 745-758, 2015 Feb 12.
Article em En | MEDLINE | ID: mdl-25662011
Impaired insulin-mediated suppression of hepatic glucose production (HGP) plays a major role in the pathogenesis of type 2 diabetes (T2D), yet the molecular mechanism by which this occurs remains unknown. Using a novel in vivo metabolomics approach, we show that the major mechanism by which insulin suppresses HGP is through reductions in hepatic acetyl CoA by suppression of lipolysis in white adipose tissue (WAT) leading to reductions in pyruvate carboxylase flux. This mechanism was confirmed in mice and rats with genetic ablation of insulin signaling and mice lacking adipose triglyceride lipase. Insulin's ability to suppress hepatic acetyl CoA, PC activity, and lipolysis was lost in high-fat-fed rats, a phenomenon reversible by IL-6 neutralization and inducible by IL-6 infusion. Taken together, these data identify WAT-derived hepatic acetyl CoA as the main regulator of HGP by insulin and link it to inflammation-induced hepatic insulin resistance associated with obesity and T2D.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Acetilcoenzima A / Resistência à Insulina / Paniculite / Fígado Idioma: En Ano de publicação: 2015 Tipo de documento: Article País de afiliação: Estados Unidos
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Acetilcoenzima A / Resistência à Insulina / Paniculite / Fígado Idioma: En Ano de publicação: 2015 Tipo de documento: Article País de afiliação: Estados Unidos