The impact and role of identified long noncoding RNAs in nonalcoholic fatty liver disease: A narrative review

Abstract

BackgroundNonalcoholic fatty liver disease (NAFLD) is the most common liver disease worldwide, but its mechanism and pathophysiology remain unclear. Long noncoding RNAs (lncRNAs) may exert a vital influence on regulating various biological functions in NAFLD.MethodsThe databases such as Google Scholar, PubMed, and Medline were searched using the following keywords: nonalcoholic fatty liver disease, nonalcoholic fatty liver disease, NAFLD, nonalcoholic steatohepatitis, nonalcoholic steatohepatitis, NASH, long noncoding RNAs, and lncRNAs. Considering the titles and abstracts, unrelated studies were excluded. The authors evaluated the full texts of the remaining studies.ResultsWe summarized the current knowledge of lncRNAs and the main signaling pathways of lncRNAs involved in NAFLD explored in recent years. As a heterogeneous group of noncoding RNAs (ncRNAs), lncRNAs play crucial roles in biological processes underlying the pathophysiology of NAFLD. The mechanisms, particularly those associated with the regulation of the expression and activities of lncRNAs, play important roles in NAFLD.ConclusionA better comprehension of the mechanism controlled by lncRNAs in NAFLD is necessary for the identification of novel therapeutic targets for drug development and improved, noninvasive methods for diagnosis.

Investigating the Role of Non-Coding RNA in Non-Alcoholic Fatty Liver Disease

“…The expression of LncARSR correlates with the activated state of PI3K/AKT/ mTOR pathway [99] miR-155 Upregulated These ncRNASs have an influence on the induction of inflammation via NF-κB pathway [100,101] Platr4 Upregulated [102] LncTNF Upregulated [103] miR-125 Upregulated…”

“…Another lncRNA that has been associated with the pathogenesis and progression of NAFLD to NASH is lncTNF. lncTNF is an intergenic lncRNA that plays a role in liver inflammation, demonstrating a robust response when subjected to TNF-α stimulation [103]. Several studies have shown an upregulation of lncTNF in NAFLD, and the main function associated with it is to promote inflammation via the NF-κB pathway [103].…”

“…lncTNF is an intergenic lncRNA that plays a role in liver inflammation, demonstrating a robust response when subjected to TNF-α stimulation [103]. Several studies have shown an upregulation of lncTNF in NAFLD, and the main function associated with it is to promote inflammation via the NF-κB pathway [103]. However, lncTNF is considered a novel ncRNA and studies regarding the involvement of lncTNF are limited.…”

Long Noncoding RNAs in Diet-Induced Metabolic Diseases

“…Recent data suggest that several lncRNAs are dysregulated in MASLD patients (for an overview, see [ 54 , 55 ]), and studies report that lncRNAs are involved in lipogenesis and fatty acid metabolism (for an overview, see [ 56 ]). Indeed, Blnc1 function is not restricted to the adipose tissue, as it has been shown to regulate lipogenesis in the liver as well [ 57 ].…”

“…Insulin resistance is often a common characteristic of obesity and diet-induced metabolic diseases, such as T2D or MASLD [ 77 ]. While a dysregulated lncRNA profile seems to be involved in the pathogenesis of diet-induced metabolic diseases such as MASLD [ 54 , 55 ], recent evidence suggests that lncRNAs also contribute to the regulation of insulin signaling and glucose metabolism in several tissues and to the pathogenesis of insulin resistance (reviewed in detail by others [ 78 , 79 ]). By controlling pathways of glucose metabolism, the liver has a major role in the control of glucose homeostasis [ 80 ], and insulin resistance seems to be associated with an increase in hepatic glucose output, lipogenesis, and VLDL secretion, leading to a combination of hyperglycemia and hypertriglyceridemia [ 81 ].…”