Nuclear Receptors Linking Metabolism, Inflammation, and Fibrosis in Nonalcoholic Fatty Liver Disease
2022
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- Autor(en) / Beteiligte
- Titel
- Nuclear Receptors Linking Metabolism, Inflammation, and Fibrosis in Nonalcoholic Fatty Liver Disease
- Ist Teil von
- International journal of molecular sciences, 2022-02, Vol.23 (5), p.2668
- Ort / Verlag
- Switzerland: MDPI AG
- Erscheinungsjahr
- 2022
- Quelle
- Free E-Journal (出版社公開部分のみ）
- Beschreibungen/Notizen
- Nonalcoholic fatty liver disease (NAFLD) and its progressive form nonalcoholic steatohepatitis (NASH) comprise a spectrum of chronic liver diseases in the global population that can lead to end-stage liver disease and hepatocellular carcinoma (HCC). NAFLD is closely linked to the metabolic syndrome, and comorbidities such as type 2 diabetes, obesity and insulin resistance aggravate liver disease, while NAFLD promotes cardiovascular risk in affected patients. The pathomechanisms of NAFLD are multifaceted, combining hepatic factors including lipotoxicity, mechanisms of cell death and liver inflammation with extrahepatic factors including metabolic disturbance and dysbiosis. Nuclear receptors (NRs) are a family of ligand-controlled transcription factors that regulate glucose, fat and cholesterol homeostasis and modulate innate immune cell functions, including liver macrophages. In parallel with metabolic derangement in NAFLD, altered NR signaling is frequently observed and might be involved in the pathogenesis. Therapeutically, clinical data indicate that single drug targets thus far have been insufficient for reaching patient-relevant endpoints. Therefore, combinatorial treatment strategies with multiple drug targets or drugs with multiple mechanisms of actions could possibly bring advantages, by providing a more holistic therapeutic approach. In this context, peroxisome proliferator-activated receptors (PPARs) and other NRs are of great interest as they are involved in wide-ranging and multi-organ activities associated with NASH progression or regression. In this review, we summarize recent advances in understanding the pathogenesis of NAFLD, focusing on mechanisms of cell death, immunometabolism and the role of NRs. We outline novel therapeutic strategies and discuss remaining challenges.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1422-0067, 1661-6596eISSN: 1422-0067DOI: 10.3390/ijms23052668Titel-ID: cdi_doaj_primary_oai_doaj_org_article_3bd012ba53de463bb8d3570ead664810
- Format
- –
- Schlagworte
- Apoptosis, Carcinoma, Hepatocellular - metabolism, Cardiovascular diseases, Cell death, Cholesterol, Combinatorial analysis, Cytokines, Diabetes mellitus (non-insulin dependent), Diabetes Mellitus, Type 2 - metabolism, Disease resistance, Dysbacteriosis, Fatty liver, Fibrosis, Hepatocellular carcinoma, Hepatocytes, Homeostasis, Humans, Immune system, Immunosuppressive agents, Inflammation, Inflammation - pathology, Insulin, Insulin resistance, Ligands, Lipids, Liver, Liver - metabolism, Liver cancer, Liver diseases, Liver Neoplasms - metabolism, Macrophages, Metabolic disorders, Metabolic syndrome, Metabolites, NAFLD, Non-alcoholic Fatty Liver Disease - metabolism, nonalcoholic steatohepatitis, Nuclear receptors, Oxidative stress, Pathogenesis, Patients, Peroxisome proliferator-activated receptors, Phosphatase, PPAR, Receptors, Cytoplasmic and Nuclear - metabolism, Review, Signal transduction, Therapeutic targets, Transcription factors