| First Author | Ishikawa H | Year | 2022 |
| Journal | Sci Rep | Volume | 12 |
| Issue | 1 | Pages | 11634 |
| PubMed ID | 35804007 | Mgi Jnum | J:326774 |
| Mgi Id | MGI:7313729 | Doi | 10.1038/s41598-022-15840-0 |
| Citation | Ishikawa H, et al. (2022) IkappaBzeta regulates the development of nonalcoholic fatty liver disease through the attenuation of hepatic steatosis in mice. Sci Rep 12(1):11634 |
| abstractText | IkappaBzeta is a transcriptional regulator that augments inflammatory responses from the Toll-like receptor or interleukin signaling. These innate immune responses contribute to the progression of nonalcoholic fatty liver disease (NAFLD); however, the role of IkappaBzeta in the pathogenesis of NAFLD remains elusive. We investigated whether IkappaBzeta was involved in the progression of NAFLD in mice. We generated hepatocyte-specific IkappaBzeta-deficient mice (Alb-Cre; Nfkbiz(fl/fl)) by crossing Nfkbiz(fl/fl) mice with Alb-Cre transgenic mice. NAFLD was induced by feeding the mice a choline-deficient, L-amino acid-defined, high-fat diet (CDAHFD). CDAHFD-induced IkappaBzeta expression in the liver was observed in Nfkbiz(fl/fl) mice, but not in Alb-Cre; Nfkbiz(fl/fl) mice. Contrary to our initial expectation, IkappaBzeta deletion in hepatocytes accelerated the progression of NAFLD after CDAHFD treatment. Although the increased expression of inflammatory cytokines and apoptosis-related proteins by CDAHFD remained unchanged between Nfkbiz(fl/fl) and Alb-Cre; Nfkbiz(fl/fl) mice, early-stage steatosis of the liver was significantly augmented in Alb-Cre; Nfkbiz(fl/fl) mice. Overexpression of IkappaBzeta in hepatocytes via the adeno-associated virus vector attenuated liver steatosis caused by the CDAHFD in wild-type C57BL/6 mice. This preventive effect of IkappaBzeta overexpression on steatosis was not observed without transcriptional activity. Microarray analysis revealed a correlation between IkappaBzeta expression and the changes of factors related to triglyceride biosynthesis and lipoprotein uptake. Our data suggest that hepatic IkappaBzeta attenuates the progression of NAFLD possibly through the regulation of the factors related to triglyceride metabolism. |
