The gene expression of long non‐coding RNAs (lncRNAs): MEG3 and H19 in adipose tissues from obese women and its association with insulin resistance and obesity indices

Abstract

Background There is evidence regarding the role of two lncRNAs: MEG3 and H19 the pathomechanism of obesity and related disorders. Here, we aimed to evaluate the expression of MEG3 and H19 in visceral adipose tissues (VAT) and subcutaneous adipose tissues (SAT) of obese women (n = 18), as compared to normal‐weight women (n = 17). Moreover, we sought to identify the association of expression of MEG3 and H19 in SAT and VAT with obesity parameters, insulin resistance, and the mRNA expression of possible target genes involved in adipogenesis and lipogenesis including peroxisome proliferator‐activated receptor gamma (PPARγ), fatty acid synthase (FAS), and acetyl‐CoA carboxylase (ACC). Methods Real‐time PCR was performed to investigate the mRNA expression of the above‐mentioned genes in VAT and SAT from all participants. Results The results showed lower mRNA levels of H19 in SAT of obese women, compared to normal‐weight women, while MEG3 expression was significantly higher in the SAT of the obese group rather than controls. Correlation analysis indicated that the transcript level of H19 had an inverse correlation with obesity indices and HOMA‐IR values. However, MEG3 expression displayed a positive correlation with all the indicated parameters in all participants. Interestingly, a positive correlation was found between transcript level of MEG3 in SAT with FAS and PPARγ. However, there was an inverse correlation between SAT expression of H19 and FAS. Conclusions It appears that lncRNAs, MEG3 and H19, are involved in obesity‐related conditions. However, more clinical studies are still required to clarify the relationships between lncRNAs with obesity and related abnormalities.

Recent Advances of LncRNA H19 in Diabetes

“…A case-control study demonstrated that lower lncRNA H19 expression, and increased miRNA-29b, a miRNA-29b expression associated with the severity of T2DM patients [17]. Moreover, an inverse correlation between the transcript level of H19 and obesity indices, HOMA-IR values and SAT expression was found in humans [18].…”

“…Glucose metabolism Hippocampal neuron apoptosis and [25] Wnt3, β-catenin, TCF-1, Bax, caspase-8, caspase-3, GSK-3β, Bel-2, Wnt signaling [28] CNS complications Glucose homeostasis and β cell function [9,[13][14] MiR-let 7, PI3K/AKT [9] H19/miR-1 40/HE4 [17] Fox O1 [18] Hnf4a [21] Diabetic cardiomyopathy Oxidative stress, inflammation, apoptosis, and autophagy [32][33] H 19/microRNA-675 axis, VDAC 1 [33,[36][37] Diabetic retinopathy Endothelial-mesenchymal transition [40] NOX4 and eNOS/NO signalings [43] Diabetic nephropathy Vitamin D receptor, miR-675 [45] EGR1 [45] Diabetic enteropathy IECs [49] MiR-141-3p, β-catenin [49] Diabetic wounds Angiogenesis [51] H 19/let-7, insulin-PI3 KA-kt pathway [9] Proliferation activity of keloid fibroblasts [53] Lymphatic endothelial cells [60] EZH2-mediated histone methylation, HIF-1a signal pathway [61] Gestational diabetes Igf2 and H 19 gene expression [13] Methylation of the H 19-Igf2 ICR [72] CNS: Central nervous system; ICR: Imprinting control region; IECs: Intestinal epithelial cells; EGR1: Early growth response protein 1.…”

Role of Long Non-Coding RNAs and the Molecular Mechanisms Involved in Insulin Resistance

“…Additionally, the expression levels of both ACC1 and FAS, two critical molecules required for fatty acid biogenesis, were elevated in obese patients. In addition, the expression of H19 was negatively correlated with FAS, suggesting the essential participation of H19 in fatty acid biogenesis [ 66 ]. On the other hand, recent studies have investigated H19 in non-invasive samples, such as blood plasma and serum.…”

“…Furthermore, in a study carried out in samples of SAT and VAT adipose tissue from women, MEG3 expression in SAT had a significant relationship with obesity indices. In addition, MEG3 expression in SAT was positively correlated with PPARγ and FAS expression ( Figure 3 ), suggesting an essential role for MEG3 in obesity-related conditions [ 66 ]. Cheng et al identified an increase in the expression of MEG3 in endothelial cells isolated from white adipose tissue compared to those from the skeletal muscle or liver of obese mice.…”

Effects of laparoscopic sleeve gastrectomy on serum lncRNA levels in obese patients

“…Specific regulations of metabolically sensitive lncRNAs in mice have been demonstrated [10]. On the other hand, the association between the expression pattern of MEG3, H19, and obesity parameters, essential genes in adipose tissues from obese women have been reported [5].…”