mTORC2 Facilitates Liver Regeneration Through Sphingolipid-Induced PPAR-α-Fatty Acid Oxidation

Michalopoulos, 2021, Liver regeneration: biological and pathological mechanisms and implications, Nat Rev Gastroenterol Hepatol, 18, 40, 10.1038/s41575-020-0342-4 Jung, 2021, TMEM9-v-ATPase activates Wnt/beta-catenin signaling via APC lysosomal degradation for liver regeneration and tumorigenesis, Hepatology, 73, 776, 10.1002/hep.31305 Campana, 2021, Liver regeneration and inflammation: from fundamental science to clinical applications, Nat Rev Mol Cell Biol, 22, 608, 10.1038/s41580-021-00373-7 He, 2021, Proliferation tracing reveals regional hepatocyte generation in liver homeostasis and repair, Science, 371, 10.1126/science.abc4346 Riddiough, 2021, Liver regeneration and liver metastasis, Semin Cancer Biol, 71, 86, 10.1016/j.semcancer.2020.05.012 Ishikawa, 2021, Growth hormone stops excessive inflammation after partial hepatectomy, Allowing liver regeneration and survival through induction of H2-Bl/HLA-G, Hepatology, 73, 759, 10.1002/hep.31297 Fernandez, 2006, Caveolin-1 is essential for liver regeneration, Science, 313, 1628, 10.1126/science.1130773 Fernandez-Rojo, 2012, Caveolin-1 orchestrates the balance between glucose and lipid-dependent energy metabolism: implications for liver regeneration, Hepatology, 55, 1574, 10.1002/hep.24810 DeAngelis, 2005, A high-fat diet impairs liver regeneration in C57BL/6 mice through overexpression of the NF-kappaB inhibitor, IkappaBalpha, Hepatology, 42, 1148, 10.1002/hep.20879 Rudnick, 2005, Trimming the fat from liver regeneration, Hepatology, 42, 1001, 10.1002/hep.20931 Kohjima, 2013, Delayed liver regeneration after partial hepatectomy in adipose differentiation related protein-null mice, J Hepatol, 59, 1246, 10.1016/j.jhep.2013.07.025 Hamano, 2014, Lipid overloading during liver regeneration causes delayed hepatocyte DNA replication by increasing ER stress in mice with simple hepatic steatosis, J Gastroenterol, 49, 305, 10.1007/s00535-013-0780-7 Newberry, 2008, Altered hepatic triglyceride content after partial hepatectomy without impaired liver regeneration in multiple murine genetic models, Hepatology, 48, 1097, 10.1002/hep.22473 Anderson, 2002, Delayed liver regeneration in peroxisome proliferator-activated receptor-alpha-null mice, Hepatology, 36, 544, 10.1053/jhep.2002.35276 Xie, 2019, Hepatocyte peroxisome proliferator-activated receptor alpha enhances liver regeneration after partial hepatectomy in mice, Am J Pathol, 189, 272, 10.1016/j.ajpath.2018.10.009 Zhao, 2020, PDK4-deficiency reprograms intrahepatic glucose and lipid metabolism to facilitate liver regeneration in mice, Hepatol Commun, 4, 504, 10.1002/hep4.1484 Saxton, 2017, mTOR signaling in growth, metabolism, and disease, Cell, 168, 960, 10.1016/j.cell.2017.02.004 Hagiwara, 2012, Hepatic mTORC2 activates glycolysis and lipogenesis through Akt, glucokinase, and SREBP1c, Cell Metab, 15, 725, 10.1016/j.cmet.2012.03.015 Guri, 2017, mTORC2 promotes tumorigenesis via lipid synthesis, Cancer Cell, 32, 807, 10.1016/j.ccell.2017.11.011 Xu, 2020, mTORC2 signaling is necessary for timely liver regeneration after partial hepatectomy, Am J Pathol, 190, 817, 10.1016/j.ajpath.2019.12.010 Hodson, 2019, The regulation of hepatic fatty acid synthesis and partitioning: the effect of nutritional state, Nat Rev Endocrinol, 15, 689, 10.1038/s41574-019-0256-9 Issemann, 1990, Activation of a member of the steroid hormone receptor superfamily by peroxisome proliferators, Nature, 347, 645, 10.1038/347645a0 Abshagen, 2018, Liver-specific Repin1 deficiency impairs transient hepatic steatosis in liver regeneration, Sci Rep, 8, 10.1038/s41598-018-35325-3 Pauta, 2016, Akt-mediated foxo1 inhibition is required for liver regeneration, Hepatology, 63, 1660, 10.1002/hep.28286 Gonzalez, 2020, AMPK and TOR: the yin and yang of cellular nutrient sensing and growth control, Cell Metab, 31, 472, 10.1016/j.cmet.2020.01.015 Sengupta, 2010, mTORC1 controls fasting-induced ketogenesis and its modulation by ageing, Nature, 468, 1100, 10.1038/nature09584 Kim, 2012, S6 kinase 2 deficiency enhances ketone body production and increases peroxisome proliferator-activated receptor alpha activity in the liver, Hepatology, 55, 1727, 10.1002/hep.25537 Mora, 2005, Deficiency of PDK1 in liver results in glucose intolerance, impairment of insulin-regulated gene expression and liver failure, Biochem J, 385, 639, 10.1042/BJ20041782 Fausto, 2006, Liver regeneration, Hepatology, 43, S45, 10.1002/hep.20969 Caldez, 2018, Metabolic remodeling during liver regeneration, Dev Cell, 47, 425, 10.1016/j.devcel.2018.09.020 Vendemiale, 1995, Mitochondrial oxidative phosphorylation and intracellular glutathione compartmentation during rat liver regeneration, Hepatology, 21, 1450, 10.1002/hep.1840210532 Clerici, 1965, Crabtree effect and the anaerobic glycolysis of the regenerating rat liver, Nature, 207, 762, 10.1038/207762a0 Forni, 1964, [Study of some aspects of liver regeneration after partial hepatectomy. I. Oxygen consumption and glycolysis of regenerating tissue], Chir Patol Sper, 12, 263 Aoyama, 2009, Pioglitazone promotes survival and prevents hepatic regeneration failure after partial hepatectomy in obese and diabetic KK-A(y) mice, Hepatology, 49, 1636, 10.1002/hep.22828 Fan, 2022, YAP-TEAD mediates peroxisome proliferator-activated receptor alpha-induced hepatomegaly and liver regeneration in mice, Hepatology, 75, 74, 10.1002/hep.32105 Eipel, 2005, Pifithrin-alpha induced p53 inhibition does not affect liver regeneration after partial hepatectomy in mice, J Hepatol, 43, 829, 10.1016/j.jhep.2005.04.018 Inoue, 2002, p53 May positively regulate hepatocyte proliferation in rats, Hepatology, 36, 336, 10.1053/jhep.2002.34942 Li, 2016, Liver serine palmitoyltransferase activity deficiency in early life impairs adherens junctions and promotes tumorigenesis, Hepatology, 64, 2089, 10.1002/hep.28845 Mitchell, 2008, A reproducible and well-tolerated method for 2/3 partial hepatectomy in mice, Nat Protoc, 3, 1167, 10.1038/nprot.2008.80 Zhang, 2015, Inhibition of wild-type p53-induced phosphatase 1 promotes liver regeneration in mice by direct activation of mammalian target of rapamycin, Hepatology, 61, 2030, 10.1002/hep.27755 Zigmond, 2007, Beta-glucosylceramide: a novel method for enhancement of natural killer T lymphocyte plasticity in murine models of immune-mediated disorders, Gut, 56, 82, 10.1136/gut.2006.095497