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The hepatic integrated stress response suppresses the somatotroph axis to control liver damage in nonalcoholic fatty liver disease.
Ohkubo, Rika; Mu, Wei-Chieh; Wang, Chih-Ling; Song, Zehan; Barthez, Marine; Wang, Yifei; Mitchener, Nathaniel; Abdullayev, Rasul; Lee, Yeong Rim; Ma, Yuze; Curtin, Megan; Srinivasan, Suraj; Zhang, Xingjia; Yang, Fanghan; Sudmant, Peter H; Pisco, Angela Oliveira; Neff, Norma; Haynes, Cole M; Chen, Danica.
Afiliação
  • Ohkubo R; Metabolic Biology Graduate Program, University of California, Berkeley, Berkeley, CA 94720, USA; Department of Nutritional Sciences and Toxicology, University of California, Berkeley, Berkeley, CA 94720, USA.
  • Mu WC; Department of Nutritional Sciences and Toxicology, University of California, Berkeley, Berkeley, CA 94720, USA; Endocrinology Graduate Program, University of California, Berkeley, Berkeley, CA 94720, USA.
  • Wang CL; Department of Nutritional Sciences and Toxicology, University of California, Berkeley, Berkeley, CA 94720, USA.
  • Song Z; Metabolic Biology Graduate Program, University of California, Berkeley, Berkeley, CA 94720, USA; Department of Nutritional Sciences and Toxicology, University of California, Berkeley, Berkeley, CA 94720, USA.
  • Barthez M; Department of Nutritional Sciences and Toxicology, University of California, Berkeley, Berkeley, CA 94720, USA.
  • Wang Y; Metabolic Biology Graduate Program, University of California, Berkeley, Berkeley, CA 94720, USA; Department of Nutritional Sciences and Toxicology, University of California, Berkeley, Berkeley, CA 94720, USA.
  • Mitchener N; Department of Nutritional Sciences and Toxicology, University of California, Berkeley, Berkeley, CA 94720, USA.
  • Abdullayev R; Department of Nutritional Sciences and Toxicology, University of California, Berkeley, Berkeley, CA 94720, USA.
  • Lee YR; Department of Nutritional Sciences and Toxicology, University of California, Berkeley, Berkeley, CA 94720, USA; Endocrinology Graduate Program, University of California, Berkeley, Berkeley, CA 94720, USA.
  • Ma Y; Department of Nutritional Sciences and Toxicology, University of California, Berkeley, Berkeley, CA 94720, USA.
  • Curtin M; Department of Nutritional Sciences and Toxicology, University of California, Berkeley, Berkeley, CA 94720, USA.
  • Srinivasan S; Department of Nutritional Sciences and Toxicology, University of California, Berkeley, Berkeley, CA 94720, USA.
  • Zhang X; Department of Nutritional Sciences and Toxicology, University of California, Berkeley, Berkeley, CA 94720, USA.
  • Yang F; Department of Nutritional Sciences and Toxicology, University of California, Berkeley, Berkeley, CA 94720, USA; Endocrinology Graduate Program, University of California, Berkeley, Berkeley, CA 94720, USA.
  • Sudmant PH; Department of Integrative Biology, University of California, Berkeley, Berkeley, CA 94720, USA; Center for Computational Biology, University of California, Berkeley, Berkeley, CA 94720, USA.
  • Pisco AO; Chan Zuckerberg Biohub, San Francisco, CA, USA.
  • Neff N; Chan Zuckerberg Biohub, San Francisco, CA, USA.
  • Haynes CM; Department of Molecular, Cell and Cancer Biology, UMass-Chan Medical School, Worcester, MA 01605, USA.
  • Chen D; Metabolic Biology Graduate Program, University of California, Berkeley, Berkeley, CA 94720, USA; Department of Nutritional Sciences and Toxicology, University of California, Berkeley, Berkeley, CA 94720, USA; Endocrinology Graduate Program, University of California, Berkeley, Berkeley, CA 94720, USA
Cell Rep ; 41(11): 111803, 2022 12 13.
Article em En | MEDLINE | ID: mdl-36516757
Nonalcoholic fatty liver disease (NAFLD) can be ameliorated by calorie restriction, which leads to the suppressed somatotroph axis. Paradoxically, the suppressed somatotroph axis is associated with patients with NAFLD and is correlated with the severity of fibrosis. How the somatotroph axis becomes dysregulated and whether the repressed somatotroph axis impacts liver damage during the progression of NAFLD are unclear. Here, we identify a regulatory branch of the hepatic integrated stress response (ISR), which represses the somatotroph axis in hepatocytes through ATF3, resulting in enhanced cell survival and reduced cell proliferation. In mouse models of NAFLD, the ISR represses the somatotroph axis, leading to reduced apoptosis and inflammation but decreased hepatocyte proliferation and exacerbated fibrosis in the liver. NAD+ repletion reduces the ISR, rescues the dysregulated somatotroph axis, and alleviates NAFLD. These results establish that the hepatic ISR suppresses the somatotroph axis to control cell fate decisions and liver damage in NAFLD.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Somatotrofos / Hepatopatia Gordurosa não Alcoólica Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Ano de publicação: 2022 Tipo de documento: Article
Texto completo
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Somatotrofos / Hepatopatia Gordurosa não Alcoólica Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Ano de publicação: 2022 Tipo de documento: Article