Scientists showed that the branched-chain fatty acids, isobutyric and isovaleric acid, increased glucose production and activated mTORC1/S6K1 in hepatocytes.
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Choi, B. S.-Y., Daniel, N., Houde, V. P., Ouellette, A., Marcotte, B., Varin, T. V., Vors, C., Feutry, P., Ilkayeva, O., Ståhlman, M., St-Pierre, P., Bäckhed, F., Tremblay, A., White, P. J., & Marette, A. (2021). Feeding diversified protein sources exacerbates hepatic insulin resistance via increased gut microbial branched-chain fatty acids and mTORC1 signaling in obese mice. Nature Communications, 12(1), 3377. https://doi.org/10.1038/s41467-021-23782-w Cite
Scientists reported the generation of a hepatobiliary tubular organoid using mouse hepatocyte progenitors and cholangiocytes.
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Tanimizu, N., Ichinohe, N., Sasaki, Y., Itoh, T., Sudo, R., Yamaguchi, T., Katsuda, T., Ninomiya, T., Tokino, T., Ochiya, T., Miyajima, A., & Mitaka, T. (2021). Generation of functional liver organoids on combining hepatocytes and cholangiocytes with hepatobiliary connections ex vivo. Nature Communications, 12(1), 3390. https://doi.org/10.1038/s41467-021-23575-1 Cite
Mechanistically, WSX1 transcriptionally downregulated an isoform of PI3K—PI3Kδ and thereby inactivated AKT, reducing AKT-induced GSK3β inhibition.
The authors assessed similarities and differences between commercially available iPSC hepatocytes and primary human hepatocytes in preliminary assays of drug metabolism, hepatotoxicity, and drug transport.
[Journal of Pharmacological and Toxicological Methods]
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Investigators showed that while ablation of ADAM17 resulted in decreased shedding of TNF RI, ADAM10 deficiency led to increased levels of soluble TNF RI in serum.
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Researchers described a study of a novel EMM composition comprising five amino acids and an amino acid derivative (Leucine, Isoleucine, Valine, Arginine, Glutamine, and N-acetylcysteine [LIVRQNac]) and its systematic evaluation across multiple NASH-relevant primary human cell model systems, including hepatocytes, macrophages, and stellate cells.
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Daou, N., Viader, A., Cokol, M., Nitzel, A., Chakravarthy, M. V., Afeyan, R., Tramontin, T., Marukian, S., & Hamill, M. J. (2021). A novel, multitargeted endogenous metabolic modulator composition impacts metabolism, inflammation, and fibrosis in nonalcoholic steatohepatitis-relevant primary human cell models. Scientific Reports, 11(1), 11861. https://doi.org/10.1038/s41598-021-88913-1 Cite
This review focuses on the role of microbiota in decompensation and strategies targeting microbiota to prevent acute decompensation.
[Journal of Hepatology]
The authors describe the mechanisms of tissue repair following damage, highlighting the close relationship between inflammation and liver regeneration, and discuss how recent findings can help design novel therapeutic approaches.
[Nature Reviews Molecular Cell Biology]
The authors provide a brief overview of iPSCs and discusses recent advances in the establishment of induced nduced tissue-specific stem cells and their possible applications in regenerative medicine.
Researchers analyzed the oxidative damage in models of liver injury characterized by biliary epithelial cells/hepatic progenitor cells (HPCs) activation and defined the impact of redox balance perturbation on HPC fate. They then identified Nuclear factor (erythroid-derived 2)-like 2 as the main transcription factor involved in the activation of HPCs.
[NPJ Regenerative Medicine]
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Researchers reported that the zinc finger transcription factor Miz1 restricted hepatocyte-driven inflammation to suppress hepatocellular carcinoma, independently of its transcriptional activity.
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Zhang, W., Zhangyuan, G., Wang, F., Jin, K., Shen, H., Zhang, L., Yuan, X., Wang, J., Zhang, H., Yu, W., Huang, R., Xu, X., Yin, Y., Zhong, G., Lin, A., & Sun, B. (2021). The zinc finger protein Miz1 suppresses liver tumorigenesis by restricting hepatocyte-driven macrophage activation and inflammation. Immunity, 0(0). https://doi.org/10.1016/j.immuni.2021.04.027 Cite