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Liver Int. 2016 Sep;36(9):1383-91. doi: 10.1111/liv.13109. Epub 2016 Mar 24.

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

Author information

1
Programa de Doctorado en Ciencias Bioquímicas, Facultad de Química, Universidad Nacional Autónoma de México (UNAM), Mexico City, Mexico.
2
Unidad de Genómica de Poblaciones Aplicada a la Salud, Facultad de Química, UNAM/Instituto Nacional de Medicina Genómica (INMEGEN), Mexico City, Mexico.
3
Departamento de Inmunología, Instituto Nacional de Cardiología "Ignacio Chávez" (INCICh), Mexico City, Mexico.
4
Departamento de Gastroenterología, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán (INCMNSZ), Mexico City, Mexico.
5
Clínica Integral de Cirugía para la Obesidad y Enfermedades Metabólicas, Hospital General "Dr. Rubén Leñero", Mexico City, Mexico.
6
Unidad de Investigación del Hígado, Fundación Clínica Médica Sur, Mexico City, Mexico.
7
Departamento Fisiología de la Nutrición, INCMNSZ, Mexico City, Mexico.
8
Laboratorio de Enfermedades Cardiovasculares, INMEGEN, Mexico City, Mexico.
9
Departamento de Patología, INCMNSZ, Mexico City, Mexico.
10
Departamento de Endocrinología y Metabolismo, INCMNSZ, Mexico City, Mexico.

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.

KEYWORDS:

ABCA1; ABCG1; miR-144; miR-33a/b - NASH

PMID:
26945479
DOI:
10.1111/liv.13109
[Indexed for MEDLINE]

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