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Research Articles Hepatocyte TLR4 triggers inter-hepatocyte Jagged1/Notch signaling to determine NASH-induced fibrosis
Aberrant hepatocyte Notch activity is critical to the development of nonalcoholic steatohepatitis (NASH)–induced liver fibrosis, but mechanisms underlying Notch reactivation in developed liver are unclear. Here, we identified that increased expression of the Notch ligand Jagged1 (JAG1) tracked with Notch activation and nonalcoholic fatty liver disease (NAFLD) activity score (NAS) in human liver biopsy specimens and mouse NASH models. The increase in Jag1 was mediated by hepatocyte Toll-like receptor 4 (TLR4)–nuclear factor B (NF-B) signaling in pericentral hepatocytes. Hepatocyte-specific Jag1 overexpression ex...
Source: Science Translational Medicine - June 23, 2021 Category: Biomedical Science Authors: Yu, J., Zhu, C., Wang, X., Kim, K., Bartolome, A., Dongiovanni, P., Yates, K. P., Valenti, L., Carrer, M., Sadowski, T., Qiang, L., Tabas, I., Lavine, J. E., Pajvani, U. B. Tags: Research Articles Source Type: research

PKC δ Silencing Alleviates Saturated Fatty Acid-Induced ER Stress by Enhancing SERCA Activity.
Conclusion : To the best of our knowledge, this is the first report demonstrating that the inhibition of PKCδ alleviates ERS by enhancing SERCA activity and stabilizing calcium homeostasis. PMID: 29046367 [PubMed - as supplied by publisher]
Source: Bioscience Reports - October 18, 2017 Category: Biomedical Science Authors: Lai S, Li Y, Kuang Y, Cui H, Yang Y, Sun W, Liu K, Chen D, Yan Q, Wen L Tags: Biosci Rep Source Type: research

Hedgehog signaling is a potent regulator of liver lipid metabolism and reveals a GLI-code associated with steatosis
This study assessed the unexpected role of the Hedgehog pathway in adult liver lipid metabolism. Using transgenic mice with conditional hepatocyte-specific deletion of Smoothened in adult mice, we showed that hepatocellular inhibition of Hedgehog signaling leads to steatosis by altering the abundance of the transcription factors GLI1 and GLI3. This steatotic 'Gli-code' caused the modulation of a complex network of lipogenic transcription factors and enzymes, including SREBP1 and PNPLA3, as demonstrated by microarray analysis and siRNA experiments and could be confirmed in other steatotic mouse models as well as in steatoti...
Source: eLife - May 17, 2016 Category: Biomedical Science Tags: Biochemistry Cell Biology Hedgehog signalling hepatocytes Human liver Mouse NAFLD smoothened steatotic Gli-code Source Type: research

Palmitate-induced Regulation of PPARγ via PGC1α: a Mechanism for Lipid Accumulation in the Liver in Nonalcoholic Fatty Liver Disease.
In conclusion, palmitate appear to up-regulate PPARγ via PGC1α in Huh7 cells, and both PGC1α and PPARγ are up-regulated in the NAFLD mice liver, suggesting an effect on lipid metabolism leading to intrahepatic triglyceride accumulation. PMID: 26941577 [PubMed - in process]
Source: International Journal of Medical Sciences - March 6, 2016 Category: Biomedical Science Tags: Int J Med Sci Source Type: research