Nuclear hormone and peptide hormone therapeutics for NAFLD and NASH
Background: Non-alcoholic steatohepatitis (NASH) is a spectrum of histological liver pathologies ranging from hepatocyte fat accumulation, hepatocellular ballooning, lobular inflammation, and pericellular fibrosis. Based on early investigations, it was discovered that visceral fat accumulation, hepa...
| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2021-04-01
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| Series: | Molecular Metabolism |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2212877820302271 |
| _version_ | 1818440123659845632 |
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| author | Brian Finan Sebastian D. Parlee Bin Yang |
| author_facet | Brian Finan Sebastian D. Parlee Bin Yang |
| author_sort | Brian Finan |
| collection | DOAJ |
| description | Background: Non-alcoholic steatohepatitis (NASH) is a spectrum of histological liver pathologies ranging from hepatocyte fat accumulation, hepatocellular ballooning, lobular inflammation, and pericellular fibrosis. Based on early investigations, it was discovered that visceral fat accumulation, hepatic insulin resistance, and atherogenic dyslipidemia are pathological triggers for NASH progression. As these pathogenic features are common with obesity, type 2 diabetes (T2D), and atherosclerosis, therapies that target dysregulated core metabolic pathways may hold promise for treating NASH, particularly as first-line treatments. Scope of Review: In this review, the latest clinical data on nuclear hormone- and peptide hormone-based drug candidates for NASH are reviewed and contextualized, culminating with a discovery research perspective on emerging combinatorial therapeutic approaches that merge nuclear and peptide strategies. Major Conclusion: Several drug candidates targeting the metabolic complications of NASH have shown promise in early clinical trials, albeit with unique benefits and challenges, but questions remain regarding their translation to larger and longer clinical trials, as well as their utility in a more diseased patient population. Promising polypharmacological approaches can potentially overcome some of these perceived challenges, as has been suggested in preclinical models, but deeper characterizations are required to fully evaluate these opportunities. |
| first_indexed | 2024-12-14T18:07:21Z |
| format | Article |
| id | doaj.art-3a242afc36c34521995d384ab94c54c3 |
| institution | Directory Open Access Journal |
| issn | 2212-8778 |
| language | English |
| last_indexed | 2024-12-14T18:07:21Z |
| publishDate | 2021-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Molecular Metabolism |
| spelling | doaj.art-3a242afc36c34521995d384ab94c54c32022-12-21T22:52:20ZengElsevierMolecular Metabolism2212-87782021-04-0146101153Nuclear hormone and peptide hormone therapeutics for NAFLD and NASHBrian Finan0Sebastian D. Parlee1Bin Yang2Corresponding author. Novo Nordisk Research Center Indianapolis, Inc., Indianapolis, IN, 46241, United States.; Novo Nordisk Research Center Indianapolis, Inc., United StatesNovo Nordisk Research Center Indianapolis, Inc., United StatesNovo Nordisk Research Center Indianapolis, Inc., United StatesBackground: Non-alcoholic steatohepatitis (NASH) is a spectrum of histological liver pathologies ranging from hepatocyte fat accumulation, hepatocellular ballooning, lobular inflammation, and pericellular fibrosis. Based on early investigations, it was discovered that visceral fat accumulation, hepatic insulin resistance, and atherogenic dyslipidemia are pathological triggers for NASH progression. As these pathogenic features are common with obesity, type 2 diabetes (T2D), and atherosclerosis, therapies that target dysregulated core metabolic pathways may hold promise for treating NASH, particularly as first-line treatments. Scope of Review: In this review, the latest clinical data on nuclear hormone- and peptide hormone-based drug candidates for NASH are reviewed and contextualized, culminating with a discovery research perspective on emerging combinatorial therapeutic approaches that merge nuclear and peptide strategies. Major Conclusion: Several drug candidates targeting the metabolic complications of NASH have shown promise in early clinical trials, albeit with unique benefits and challenges, but questions remain regarding their translation to larger and longer clinical trials, as well as their utility in a more diseased patient population. Promising polypharmacological approaches can potentially overcome some of these perceived challenges, as has been suggested in preclinical models, but deeper characterizations are required to fully evaluate these opportunities.http://www.sciencedirect.com/science/article/pii/S2212877820302271Nuclear hormonePeptide hormoneNAFLDNASHClinical data |
| spellingShingle | Brian Finan Sebastian D. Parlee Bin Yang Nuclear hormone and peptide hormone therapeutics for NAFLD and NASH Molecular Metabolism Nuclear hormone Peptide hormone NAFLD NASH Clinical data |
| title | Nuclear hormone and peptide hormone therapeutics for NAFLD and NASH |
| title_full | Nuclear hormone and peptide hormone therapeutics for NAFLD and NASH |
| title_fullStr | Nuclear hormone and peptide hormone therapeutics for NAFLD and NASH |
| title_full_unstemmed | Nuclear hormone and peptide hormone therapeutics for NAFLD and NASH |
| title_short | Nuclear hormone and peptide hormone therapeutics for NAFLD and NASH |
| title_sort | nuclear hormone and peptide hormone therapeutics for nafld and nash |
| topic | Nuclear hormone Peptide hormone NAFLD NASH Clinical data |
| url | http://www.sciencedirect.com/science/article/pii/S2212877820302271 |
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