{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T22:27:50Z","timestamp":1783376870193,"version":"3.54.6"},"reference-count":54,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2023,8,28]],"date-time":"2023-08-28T00:00:00Z","timestamp":1693180800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Washington State Andy Hill CARE Fund","award":["R35 CA197222"],"award-info":[{"award-number":["R35 CA197222"]}]},{"DOI":"10.13039\/100000054","name":"National Institutes of Health, National Cancer Institute","doi-asserted-by":"publisher","award":["R35 CA197222"],"award-info":[{"award-number":["R35 CA197222"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Lipodystrophy is a disorder featuring loss of normal adipose tissue depots due to impaired production of normal adipocytes. It leads to a gain of fat deposition in ectopic tissues such as liver and skeletal muscle that results in steatosis, dyslipidemia, and insulin resistance. Previously, we established a Rosa NIC\/NIC::AdiCre lipodystrophy model mouse. The lipodystrophic phenotype that included hepatomegaly accompanied with hepatic damage due to higher lipid accumulation was attenuated substantially by amplified systemic NRF2 signaling in mice with hypomorphic expression of Keap1; whole-body Nrf2 deletion abrogated this protection. To determine whether hepatic-specific NRF2 signaling would be sufficient for protection against hepatomegaly and fatty liver development, direct, powerful, transient expression of Nrf2 or its target gene Nqo1 was achieved by administration through hydrodynamic tail vein injection of pCAG expression vectors of dominant-active Nrf2 and Nqo1 in Rosa NIC\/NIC::AdiCre mice fed a 9% fat diet. Both vectors enabled protection from hepatic damage, with the pCAG-Nqo1 vector being the more effective as seen with a ~50% decrease in hepatic triglyceride levels. Therefore, activating NRF2 signaling or direct elevation of NQO1 in the liver provides new possibilities to partially reduce steatosis that accompanies lipodystrophy.<\/jats:p>","DOI":"10.3390\/ijms241713345","type":"journal-article","created":{"date-parts":[[2023,8,29]],"date-time":"2023-08-29T08:26:52Z","timestamp":1693297612000},"page":"13345","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Forced Hepatic Expression of NRF2 or NQO1 Impedes Hepatocyte Lipid Accumulation in a Lipodystrophy Mouse Model"],"prefix":"10.3390","volume":"24","author":[{"given":"Nobunao","family":"Wakabayashi","sequence":"first","affiliation":[{"name":"Translational Research Program, Fred Hutchinson Cancer Center, Seattle, WA 98109, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoko","family":"Yagishita","sequence":"additional","affiliation":[{"name":"Translational Research Program, Fred Hutchinson Cancer Center, Seattle, WA 98109, USA"},{"name":"Division of Endocrinology, Columbia University, New York, NY 10032, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-9251-242X","authenticated-orcid":false,"given":"Tanvi","family":"Joshi","sequence":"additional","affiliation":[{"name":"Translational Research Program, Fred Hutchinson Cancer Center, Seattle, WA 98109, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6676-261X","authenticated-orcid":false,"given":"Thomas W.","family":"Kensler","sequence":"additional","affiliation":[{"name":"Translational Research Program, Fred Hutchinson Cancer Center, Seattle, WA 98109, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,8,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"522","DOI":"10.1038\/nrendo.2015.123","article-title":"Congenital generalized lipodystrophies\u2014New insights into metabolic dysfunction","volume":"11","author":"Patni","year":"2015","journal-title":"Nat. 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