Hepatic miR-33a/miR-144 and their target gene ABCA1 are associated with steatohepatitis in morbidly obese subjects.

Abstract

BACKGROUND AND AIM:

Abnormal cholesterol metabolism may contribute to the pathogenesis of non-alcoholic steatohepatitis (NASH) and fibrosis. miR-33 and miR-144 regulate adenosine triphosphate binding cassette transporter (ABCA1) and other target genes involved in cholesterol efflux, fatty acid oxidation and inflammation. We explored relationships between non-alcoholic fatty liver disease (NAFLD) and the hepatic expression of ABCA1/ABCG1, as well as other target genes regulated by miR-33 (carnitine O-octanoyltransferase, CROT and hydroxyacyl-CoA-dehydrogenase β-subunit, HADHB) and miR-144 (toll-like receptor-2, TLR2). Moreover, we evaluated whether the expression of these genes is correlated with miR-33a/b and miR-144 expression in Mexican individuals with morbid obesity.

METHODS:

Eighty-four morbidly obese subjects undergoing bariatric surgery were included in this study. Liver biopsies were obtained to measure hepatic triglyceride and free cholesterol contents, as well as ABCA1, ABCG1, CROT, HADHB, TLR2, miR-33a/b and miR-144 expression.

RESULTS:

Hepatic free cholesterol content was significantly increased in NASH as compared to non-NASH subjects, while ABCA1 and ABCG1 protein levels significantly decreased with NASH and fibrosis progression. The relative expression of miR-33a and miR-144 correlated inversely with ABCA1 but not with ABCG1 protein levels. Moreover, both miRNAs increased significantly in NASH individuals. miR-33 target genes CROT and HADHB correlated inversely with miR-33a. However, the expression of these genes was not associated with NASH.

CONCLUSIONS:

miR-33a/144 and their target gene ABCA1 may contribute to the pathogenesis of NASH in morbidly obese subjects.

• Authors: Joel Vega-Badillo, Roxana Gutiérrez-Vidal, Hugo A Hernández-Pérez, Hugo Villamil-Ramírez, Paola León-Mimila, Fausto Sánchez-Muñoz, Sofía Morán-Ramos, Elena Larrieta-Carrasco, Itzel Fernández-Silva, Nahúm Méndez-Sánchez, Armando R Tovar, Francisco Campos-Pérez, Teresa Villarreal-Molina, Rogelio Hernández-Pando, Carlos A Aguilar-Salinas, Samuel Canizales-Quinteros
• Journal: Liver international : official journal of the International Association for the Study of the Liver (Liver Int) Vol. 36 Issue 9 Pg. 1383-91 (09 2016) ISSN: 1478-3231 [Electronic] United States
• PMID: 26945479 (Publication Type: Journal Article)
• Copyright: © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Chemical References

• ABCA1 protein, human
• ABCG1 protein, human
• ATP Binding Cassette Transporter 1
• ATP Binding Cassette Transporter, Subfamily G, Member 1
• MIRN144 microRNA, human
• MIRN33a microRNA, human
• MicroRNAs
• Triglycerides
• Cholesterol

Topics

• ATP Binding Cassette Transporter 1 (genetics)
• ATP Binding Cassette Transporter, Subfamily G, Member 1 (genetics)
• Adult
• Bariatric Surgery
• Cholesterol (metabolism)
• Female
• Gene Expression
• Humans
• Immunohistochemistry
• Liver (metabolism, pathology)
• Male
• Mexico
• MicroRNAs (genetics)
• Middle Aged
• Non-alcoholic Fatty Liver Disease (genetics, pathology)
• Obesity, Morbid (complications, surgery)
• Triglycerides (metabolism)
• Young Adult