ArticlePloS one2017
Attenuated lipotoxicity and apoptosis is linked to exogenous and endogenous augmenter of liver regeneration by different pathways.
Article in PloS one, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 36 citations in OpenAlex.
- A stress-adaptive lipid kinase axis defines metabolic vulnerabilities in neuroendocrine prostate cancer.Cancer cell · 2026Article
- A Stress-Adaptive Lipid Kinase Axis Defines Metabolic Vulnerabilities in Neuroendocrine Prostate Cancer.bioRxiv : the preprint server for biology · 2026Article
- ADAM17, induced by Augmenter of Liver Regeneration via G protein-coupled receptor activation, transactivates epidermal growth factor-receptor and reduces classical IL-6 signaling.Cell communication and signaling : CCS · 2026Article
- Hepatocyte nuclear factors dynamically regulate triglyceride metabolic reprogramming in metabolic dysfunction-associated steatotic liver disease: Mechanisms and implications.World journal of hepatology · 2025Review
- Antioxidant and Anti-Inflammatory Effects ofAntioxidants (Basel, Switzerland) · 2024Article
- Hepatic Amyloid Beta-42-Metabolizing Proteins in Liver Steatosis and Metabolic Dysfunction-Associated Steatohepatitis.International journal of molecular sciences · 2024Article
- Saturated Fat-Mediated Upregulation of IL-32 and CCL20 in Hepatocytes Contributes to Higher Expression of These Fibrosis-Driving Molecules in MASLD.International journal of molecular sciences · 2023Article
- Beyond energy provider: multifunction of lipid droplets in embryonic development.Biological research · 2023Review
- Interleukin-1ß Attenuates Expression of Augmenter of Liver Regeneration (ALR) by Regulating HNF4α Independent of c-Jun.International journal of molecular sciences · 2023Article
- Relationship between obesity related indicators and non-alcoholic fatty liver disease in children: a systematic review and meta-analysis.Translational pediatrics · 2023Article
- Cardiac Hepatopathy: New Perspectives on Old Problems through a Prism of Endogenous Metabolic Regulations by Hepatokines.Antioxidants (Basel, Switzerland) · 2023Review
- The role of FOXA family transcription factors in glucolipid metabolism and NAFLD.Frontiers in endocrinology · 2023Review
- The protective roles of augmenter of liver regeneration in hepatocytes in the non-alcoholic fatty liver disease.Frontiers in pharmacology · 2022Review
- Blocking the short isoform of augmenter of liver regeneration inhibits proliferation of human multiple myeloma U266 cells via the MAPK/STAT3/cell cycle signaling pathway.Oncology letters · 2021Article
- Upregulation Mitochondrial Carrier 1 (MTCH1) Is Associated with Cell Proliferation, Invasion, and Migration of Liver Hepatocellular Carcinoma.BioMed research international · 2021Article
- Lack of Augmenter of Liver Regeneration Disrupts Cholesterol Homeostasis of Liver in Mice by Inhibiting the AMPK Pathway.Hepatology communications · 2020Article
- rs953413 Regulates Polyunsaturated Fatty Acid Metabolism by Modulating ELOVL2 Expression.iScience · 2020Article
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- Lipid storage droplet protein 5 reduces sodium palmitate‑induced lipotoxicity in human normal liver cells by regulating lipid metabolism‑related factors.Molecular medicine reports · 2019Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Nonalcoholic fatty liver disease (NAFLD) covers a spectrum from simple steatosis to nonalcoholic steatohepatitis (NASH) and cirrhosis. Free fatty acids (FFA) induce steatosis and lipo-toxicity and correlate with severity of NAFLD. In this study we aimed to investigate the role of exogenous and endogenous ALR (augmenter of liver regeneration) for FFA induced ER (endoplasmatic reticulum) -stress and lipoapoptosis. Primary human hepatocytes or hepatoma cells either treated with recombinant human ALR (rhALR, 15kDa) or expressing short form ALR (sfALR, 15kDa) were incubated with palmitic acid (PA) and analyzed for lipo-toxicity, -apoptosis, activation of ER-stress response pathways, triacylglycerides (TAG), mRNA and protein expression of lipid metabolizing genes. Both, exogenous rhALR and cytosolic sfALR reduced PA induced caspase 3 activity and Bax protein expression and therefore lipotoxicity. Endogenous sfALR but not rhALR treatment lowered TAG levels, diminished activation of ER-stress mediators C-Jun N-terminal kinase (JNK), X-box binding protein-1 (XBP1) and proapoptotic transcription factor C/EBP-homologous protein (CHOP), and reduced death receptor 5 protein expression. Cellular ALR exerts its lipid lowering and anti-apoptotic actions by enhancing FABP1, which binds toxic FFA, increasing mitochondrial β-oxidation by elevating the mitochondrial FFA transporter CPT1α, and decreasing ELOVL6, which delivers toxic FFA metabolites. We found reduced hepatic mRNA levels of ALR in a high fat diet mouse model, and of ALR and FOXA2, a transcription factor inducing ALR expression, in human steatotic as well as NASH liver samples, which may explain increased lipid deposition and reduced β-oxidation in NASH patients. Present study shows that exogenous and endogenous ALR reduce PA induced lipoapoptosis. Furthermore, cytosolic sfALR changes mRNA and protein expression of genes regulating lipid metabolism, reduces ER-stress finally impeding progression of NASH.
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