1 40 1 Text A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text. URL Address <a href="http://doi.org/10.1172/jci96324" target="_blank" rel="noreferrer noopener">http://doi.org/10.1172/jci96324</a> Rights Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s). Pages 4449-4461 Issue 12 Volume 127 Search for Full-text Locate full-text within NEOMED Library's e-journal collections <p>Users with a NEOMED Library login can search for full-text journal articles at the following url: <a href="https://libraryguides.neomed.edu/home">https://libraryguides.neomed.edu/home</a></p> Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Hepatic Neuregulin 4 Signaling Defines An Endocrine Checkpoint For Steatosis-to-nash Progression Publisher An entity responsible for making the resource available Journal of Clinical Investigation Date A point or period of time associated with an event in the lifecycle of the resource 2017 2017-12 Subject The topic of the resource alpha-induced apoptosis; association; brown; fatty liver-disease; Inflammation; mice; necroptosis; necrotic cell-death; nonalcoholic steatohepatitis; pathogenesis; Research & Experimental Medicine Creator An entity primarily responsible for making the resource Guo L; Zhang P; Chen Z M; Xia H J; Li S M; Zhang Y Q; Kobberup S; Zou W P; Lin J D Description An account of the resource Nonalcoholic steatohepatitis (NASH) is characterized by progressive liver injury, inflammation, and fibrosis; however, the mechanisms that govern the transition from hepatic steatosis, which is relatively benign, to NASH remain poorly defined. Neuregulin 4 (Nrg4) is an adipose tissue-enriched endocrine factor that elicits beneficial metabolic effects in obesity. Here, we show that Nrg4 is a key component of an endocrine checkpoint that preserves hepatocyte health and counters diet-induced NASH in mice. Nrg4 deficiency accelerated liver injury, fibrosis, inflammation, and cell death in a mouse model of NASH. In contrast, transgenic expression of Nrg4 in adipose tissue alleviated diet-induced NASH. Nrg4 attenuated hepatocyte death in a cell-autonomous manner by blocking ubiquitination and proteasomal degradation of c-FLIPL, a negative regulator of cell death. Adeno-associated virus-mediated (AAV-mediated) rescue of hepatic c-FLIPL expression in Nrg4-deficent mice functionally restored the brake for steatosis to NASH transition. Thus, hepatic Nrg4 signaling serves as an endocrine checkpoint for steatosis-to-NASH progression by activating a cytoprotective pathway to counter stress-induced liver injury. Identifier An unambiguous reference to the resource within a given context <a href="http://doi.org/10.1172/jci96324" target="_blank" rel="noreferrer noopener">10.1172/jci96324</a> Format The file format, physical medium, or dimensions of the resource Journal Article or Conference Abstract Publication 2017 alpha-induced apoptosis association brown Chen Z M fatty liver-disease Guo L Inflammation Journal Article or Conference Abstract Publication Journal of Clinical Investigation Kobberup S Li S M Lin J D Mice Necroptosis necrotic cell-death Nonalcoholic steatohepatitis Pathogenesis Research & Experimental Medicine Xia H J Zhang P Zhang Y Q Zou W P