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.
Pubmed ID: 36516757 RIS Download
Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.
A Python-based environment of open-source software for mathematics, science, and engineering. The core packages of SciPy include: NumPy, a base N-dimensional array package; SciPy Library, a fundamental library for scientific computing; and IPython, an enhanced interactive console.
View all literature mentionsSoftware for single-cell flow cytometry analysis. Its functions include management, display, manipulation, analysis and publication of the data stream produced by flow and mass cytometers.
View all literature mentionsSoftware package for the analysis of gene expression microarray data, especially the use of linear models for analyzing designed experiments and the assessment of differential expression.
View all literature mentionsMus musculus with name C57BL/6J from IMSR.
View all literature mentionsCell line HEK293T is a Transformed cell line with a species of origin Homo sapiens (Human)
View all literature mentionsThis monoclonal targets GAPDH
View all literature mentionsThis polyclonal targets eIF2 alpha
View all literature mentionsThis monoclonal targets Ki-67
View all literature mentionsThis polyclonal secondary targets IgG (H+L)
View all literature mentionsThis monoclonal targets CD68
View all literature mentionsThis isotype control targets not applicable
View all literature mentionsThis monoclonal targets ATF-3
View all literature mentionsThis polyclonal targets FGF acidic/FGF1
View all literature mentionsThis polyclonal targets Mouse Growth Hormone R
View all literature mentionsThis polyclonal targets Actin
View all literature mentionsThis polyclonal targets Phospho-Akt (Ser473)
View all literature mentionsThis polyclonal targets eIF2a, phospho (Ser52)
View all literature mentions