Differential expression of miRNAs in the visceral adipose tissue of patients with non‐alcoholic fatty liver disease

Abstract

Aliment Pharmacol Ther 2010; 32: 487–497SummaryBackground Progression of non‐alcoholic fatty liver disease (NAFLD) can be facilitated by soluble molecules secreted by visceral adipose tissue (VAT). MicroRNAs (miRNAs) are likely to regulate some of these molecular pathways involved in pathogenesis of NAFLD.Aim To profile miRNA expression in the visceral adipose tissue of patients with NAFLD.Methods Visceral adipose tissue samples were collected from NAFLD patients and frozen. Patients with biopsy‐proven NAFLD were divided into non‐alcoholic steatohepatitis (NASH) (n = 12) and non‐NASH (n = 12) cohorts controlled for clinical and demographic characteristics. Extracted total RNA was profiled using TaqMan Human MicroRNA arrays. Univariate Mann–Whitney comparisons and multivariate regression analysis were performed to compare miRNA profiles.Results A total of 113 miRNA differentially expressed between NASH patients and non‐NASH patients (P < 0.05). Of these, seven remained significant after multiple test correction (hsa‐miR‐132, hsa‐miR‐150, hsa‐miR‐433, hsa‐miR‐28‐3p, hsa‐miR‐511, hsa‐miR‐517a, hsa‐miR‐671). Predicted target genes for these miRNAs include insulin receptor pathway components (IGF1, IGFR13), cytokines (CCL3, IL6), ghrelin/obestatin gene, and inflammation‐related genes (NFKB1, RELB, FAS). In addition, two miRNA species, hsa‐miR‐197 and hsa‐miR‐99, were significantly associated with pericellular fibrosis in NASH patients (P < 0.05). Levels of IL‐6 in the serum negatively correlated with the expression levels of all seven miRNAs capable of down regulating IL‐6 encoding gene.Conclusions miRNA expression from VAT may contribute to the pathogenesis of NAFLD – a finding which may distinguish relatively simple steatosis from NASH. This could help identify potential targets for pharmacological treatment regimens and candidate biomarkers for NASH.

A role for miR-296 in the regulation of lipoapoptosis by targeting PUMA

“…Reduced miR-296-5p levels in obese patients with or without NAFLD signifi cantly correlate with increased expression of PUMA, possibly linking miR-296-5p-regulated PUMA expression with increased hepatocyte apoptosis in human NAFLD. Consistent with these results, miR-296-5p levels are also decreased in the visceral adipose tissue of patients with NAFLD ( 27 ) and may contribute to the adipocyte apoptosis associated with human obesity ( 28 ). Finally, the involvement of miR-296-5p in fatty liver disease is also supported by the observation that a region on human chromosome 20, including the intergenic locus coding for miR-296-5p (20q13.3), is linked to human obesity ( 29 ).…”

Circulating microRNAs in patients with non-alcoholic fatty liver disease

“…miR-181d may play a role in regulating the lipid content of hepatocytes [9] . miR-197 and miR-99, in the visceral adipose tissue, were significantly associated with pericellular fibrosis in NAFLD [10] . Serum free fatty acid (FFA) levels negatively correlated with adipose tissue level of miR-99a [11] .…”

“…In our study, serum levels of miR-181d were decreased in NAFLD by 2.49-fold compared to controls. Estep et al [10] studied miRNA expression in the visceral adipose tissue of patients with NAFLD. They found that significant changes in miRNA expression were characterized by overall down-regulation in the visceral adipose tissue.…”

Assessment of non‐alcoholic fatty liver disease using serum total cell death and apoptosis markers

“…[9][10][11][12][13][14][15][16] 21,22 Our previous study revealed that M30 has high overall accuracy in differentiating NAFLD from control subjects and moderate accuracy in differentiating NASH from simple steatosis. 20 Recent studies suggest that other cell death markers may also be useful in the prediction of NASH.…”