Hepatic Nuclear Receptor Expression Associates with Features of Histology in Pediatric Nonalcoholic Fatty Liver Disease
Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in children and adults. This study examined the relationship between hepatic nuclear receptor (NR) expression and histologic features of NAFLD. Drugs targeting a variety of NRs for nonalcoholic steatohepatitis...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wolters Kluwer Health/LWW
2018-10-01
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| Series: | Hepatology Communications |
| Online Access: | https://doi.org/10.1002/hep4.1232 |
| _version_ | 1797934515997376512 |
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| author | Erin E. Elbel Joel E. Lavine Michael Downes Mark Van Natta Ruth Yu Jeffrey B. Schwimmer Cynthia Behling Elizabeth M. Brunt James Tonascia Ronald Evans |
| author_facet | Erin E. Elbel Joel E. Lavine Michael Downes Mark Van Natta Ruth Yu Jeffrey B. Schwimmer Cynthia Behling Elizabeth M. Brunt James Tonascia Ronald Evans |
| author_sort | Erin E. Elbel |
| collection | DOAJ |
| description | Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in children and adults. This study examined the relationship between hepatic nuclear receptor (NR) expression and histologic features of NAFLD. Drugs targeting a variety of NRs for nonalcoholic steatohepatitis (NASH) are in clinical trials. Liver messenger RNA was isolated from 40 children (10‐19 years) undergoing end‐of‐treatment biopsy in the Treatment of NAFLD in Children (TONIC) trial. High‐throughput quantitative polymerase chain reaction assayed NR messenger RNA. Cluster analysis was used to group 36 NRs, and NR levels were related to histologic measures of specific NAFLD features. Cluster analysis determined five groupings of NRs. Significant (P < 0.05) differential expressions of specific NRs associated with histologic measures include farnesoid X receptor alpha and retinoic acid receptor (RARβ and RARβ) for steatosis; estrogen receptor alpha (ERα) and peroxisome proliferator‐activated receptor gamma 3 (PPARγ3) for hepatocellular ballooning; ER and PPARγ2 for lobular inflammation; PPARα/δ/γ1/γ2, ERα, constitutive androstane receptor, chicken ovalbumin upstream promoter transcription factor 1, RARα, RARβ1, retinoid X receptor, pregnane X receptor, thyroid hormone receptors α and β, and nuclear receptor related‐1 for fibrosis; and ERα and RARβ/β1/α for diagnosis of NASH. Conclusion: Differential expression of specific NRs correlates with histologic severity of specific NAFLD features. These NRs are pleiotropic transactivators regulating basal metabolic functions and inflammatory responses. Derangement of activity of these receptors in NAFLD provides a rationale for exploiting their ability with receptor‐specific ligands to ameliorate NASH and its consequences. |
| first_indexed | 2024-04-10T18:01:20Z |
| format | Article |
| id | doaj.art-20fc19426e1640138580ec86b1c18716 |
| institution | Directory Open Access Journal |
| issn | 2471-254X |
| language | English |
| last_indexed | 2024-04-10T18:01:20Z |
| publishDate | 2018-10-01 |
| publisher | Wolters Kluwer Health/LWW |
| record_format | Article |
| series | Hepatology Communications |
| spelling | doaj.art-20fc19426e1640138580ec86b1c187162023-02-02T15:24:47ZengWolters Kluwer Health/LWWHepatology Communications2471-254X2018-10-012101213122610.1002/hep4.1232Hepatic Nuclear Receptor Expression Associates with Features of Histology in Pediatric Nonalcoholic Fatty Liver DiseaseErin E. Elbel0Joel E. Lavine1Michael Downes2Mark Van Natta3Ruth Yu4Jeffrey B. Schwimmer5Cynthia Behling6Elizabeth M. Brunt7James Tonascia8Ronald Evans9Department of Pediatrics Columbia University New York NYDepartment of Pediatrics Columbia University New York NYGene Expression Laboratory The Salk Institute La Jolla CABloomberg School of Public Health Johns Hopkins University Baltimore MDGene Expression Laboratory The Salk Institute La Jolla CADepartment of Pediatrics University of California,San Diego San Diego CADepartment of Pediatrics University of California,San Diego San Diego CADepartment of Pathology and Immunology Washington University St. Louis MOBloomberg School of Public Health Johns Hopkins University Baltimore MDGene Expression Laboratory The Salk Institute La Jolla CANonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in children and adults. This study examined the relationship between hepatic nuclear receptor (NR) expression and histologic features of NAFLD. Drugs targeting a variety of NRs for nonalcoholic steatohepatitis (NASH) are in clinical trials. Liver messenger RNA was isolated from 40 children (10‐19 years) undergoing end‐of‐treatment biopsy in the Treatment of NAFLD in Children (TONIC) trial. High‐throughput quantitative polymerase chain reaction assayed NR messenger RNA. Cluster analysis was used to group 36 NRs, and NR levels were related to histologic measures of specific NAFLD features. Cluster analysis determined five groupings of NRs. Significant (P < 0.05) differential expressions of specific NRs associated with histologic measures include farnesoid X receptor alpha and retinoic acid receptor (RARβ and RARβ) for steatosis; estrogen receptor alpha (ERα) and peroxisome proliferator‐activated receptor gamma 3 (PPARγ3) for hepatocellular ballooning; ER and PPARγ2 for lobular inflammation; PPARα/δ/γ1/γ2, ERα, constitutive androstane receptor, chicken ovalbumin upstream promoter transcription factor 1, RARα, RARβ1, retinoid X receptor, pregnane X receptor, thyroid hormone receptors α and β, and nuclear receptor related‐1 for fibrosis; and ERα and RARβ/β1/α for diagnosis of NASH. Conclusion: Differential expression of specific NRs correlates with histologic severity of specific NAFLD features. These NRs are pleiotropic transactivators regulating basal metabolic functions and inflammatory responses. Derangement of activity of these receptors in NAFLD provides a rationale for exploiting their ability with receptor‐specific ligands to ameliorate NASH and its consequences.https://doi.org/10.1002/hep4.1232 |
| spellingShingle | Erin E. Elbel Joel E. Lavine Michael Downes Mark Van Natta Ruth Yu Jeffrey B. Schwimmer Cynthia Behling Elizabeth M. Brunt James Tonascia Ronald Evans Hepatic Nuclear Receptor Expression Associates with Features of Histology in Pediatric Nonalcoholic Fatty Liver Disease Hepatology Communications |
| title | Hepatic Nuclear Receptor Expression Associates with Features of Histology in Pediatric Nonalcoholic Fatty Liver Disease |
| title_full | Hepatic Nuclear Receptor Expression Associates with Features of Histology in Pediatric Nonalcoholic Fatty Liver Disease |
| title_fullStr | Hepatic Nuclear Receptor Expression Associates with Features of Histology in Pediatric Nonalcoholic Fatty Liver Disease |
| title_full_unstemmed | Hepatic Nuclear Receptor Expression Associates with Features of Histology in Pediatric Nonalcoholic Fatty Liver Disease |
| title_short | Hepatic Nuclear Receptor Expression Associates with Features of Histology in Pediatric Nonalcoholic Fatty Liver Disease |
| title_sort | hepatic nuclear receptor expression associates with features of histology in pediatric nonalcoholic fatty liver disease |
| url | https://doi.org/10.1002/hep4.1232 |
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