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Fig. 3. (A) Schematic diagram of possible regulation of miR-181b-5p and miR-330-3p through their transcription factors. Downregulation of miR-330-3p reduces the inhibition of high-mobility group AT-hook 2 (HMGA2),28 which induces transforming growth factor-β (TGF-β) signalling through mothers against decapentaplegic homolog 3 (SMAD3). Again, miR-181b-5p overexpression reduces SMAD7, which further induces the receptor-activated SMADs (R-SMADs). Overexpressed HMGA2 causes an increase in CCAAT enhancer binding protein beta (CEBPB).30 CEBPB, a cytokine-inducible transcription factor, is also stimulated by the presence of a pro-inflammatory state in the diseased condition.32 This has a two-fold action: inducing the miR-181b-5p promoter and aggravating the peroxisome proliferator-activated receptor gamma (PPARγ) pathway through E2F transcription factor 1 (E2F1) activity. The latter is also affected by dysregulated miR-330-3p.24,30 Phosphatase and tensin homolog (PTEN) antagonizes the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) pathway by reconverting phosphatidylinositol-3,4,5-triphosphate (PIP3) back to phosphatidylinositol 3,4-bisphosphate (PIP2). Therefore, regulation of insulin function is performed by the balance between phosphorylation and dephosphorylation. Several microRNAs (miRNAs) are known to target PTEN and overexpress and modulate TGF-β and AKT activation. Overall, this results in cellular proliferation and increased adipogenesis, β-cell destruction, and insulin resistance, leading to a type 2 diabetes mellitus (T2DM) state. (B) The gene expression for messenger RNA (mRNA) and miRNA in visceral adipose tissue (VAT) and peripheral blood. GDF-15, growth differentiation factor-15; GFRAL, glial cell-derived neurotrophic factor receptor-alpha-like; YY1, Yin Yang 1; TβR, TGF-β receptor; GLUT4, glucose transporter type 4; HOMA, homeostatic model assessment; TG, triglyceride; HDL, high-density lipoprotein; TyG, triglyceride glucose.
J Obes Metab Syndr 2023;32:64~76 https://doi.org/10.7570/jomes22010
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