miR33a/miR33b* and miR122 as Possible Contributors to Hepatic Lipid Metabolism in Obese Women with Nonalcoholic Fatty Liver Disease

Abstract

Specific miRNA expression profiles have been shown to be associated with nonalcoholic fatty liver disease (NAFLD). We examined the correlation between the circulating levels and hepatic expression of miR122 and miR33a/b*, the key lipid metabolism-related gene expression and the clinicopathological factors of obese women with NAFLD. We measured miR122 and miR33a/b* expression in liver samples from 62 morbidly obese (MO), 30 moderately obese (ModO), and eight normal-weight controls. MiR122 and miR33a/b* expression was analyzed by qRT-PCR. Additionally, miR122 and miR33b* circulating levels were analyzed in 122 women. Hepatic miR33b* expression was increased in MO compared to ModO and controls, whereas miR122 expression was decreased in the MO group compared to ModO. In obese cohorts, miR33b* expression was increased in nonalcoholic steatohepatitis (NASH). Regarding circulating levels, MO patients with NASH showed higher miR122 levels than MO with simple steatosis (SS). These circulating levels are good predictors of histological features associated with disease severity. MO is associated with altered hepatic miRNA expression. In obese women, higher miR33b* liver expression is associated with NASH. Moreover, multiple correlations between miRNAs and the expression of genes related to lipid metabolism were found, that would suggest a miRNA-host gene circuit. Finally, miR122 circulating levels could be included in a panel of different biomarkers to improve accuracy in the non-invasive diagnosis of NASH.

Systematic integrative analysis of gene expression identifies HNF4A as the central gene in pathogenesis of non-alcoholic steatohepatitis

“…in various cancers, including liver cancer[ 24 ], abdominal, epithelial cancer, inflammation, diabetes[ 25 ], etc. The microRNAs miR-122, together with miR-133-a, miR-134-a and miR-24, conveniently detectable also in serum and plasma, have recently been reported as biomarkers for hepatic inflammation, contributing to NASH development[ 26 , 27 ]. Similar roles, plus activation in various infections by viruses are reported for IFN Beta[ 28 ].…”

Hepcidin in morbidly obese women with non-alcoholic fatty liver disease

“…In our previous studies, we showed that lipogenesis seems to be downregulated in advanced stages of simple steatosis [ 4 ], as well as the hepatic lipid metabolism seems to be “controlled” by some miRNAs in patients with NAFLD [ 37 ]. As both the lipid and the iron metabolism seem to be involved in the pathogenesis of NAFLD [ 28 , 32 ], hepcidin seems to have a role in transition from steatosis to NASH [ 23 ] and lipid metabolism might be involved in hepcidin synthesis [ 28 , 32 ], in the present work we aimed to go one step further by exploring the relationship between plasma hepcidin levels, and the presence of NAFLD in morbidly obese patients, and also if any association between the hepatic expression of the main iron and lipid metabolism-related genes exists.…”

The Emerging Role of MicroRNAs in NAFLD: Highlight of MicroRNA-29a in Modulating Oxidative Stress, Inflammation, and Beyond

“…Since Lee et al firstly identified the critical function of miRs in regulating the development of C. elegans [57], mounting lines of evidence have revealed that miRs are pivotal for controlling metabolic homeostasis and represents relevance in diagnosing liver diseases. miR-122, which is the most abundant miRs in the liver, is involved in hepatic cholesterol and lipid metabolism [58], and presented an increased level in circulation in the context of NAFLD [59][60][61][62], making a well predictive panel when combined with miR-29a [29]. Moreover, dysregulated level of circulating miRs were also reported, including miR-122 [29], miR-34a [61,63], miR-33 [62], miR-21 [64], miR-192 [60], miR-221/222 [65], miR-375 [59], and miR-802 [66].…”