MicroRNAs as Epigenetic Regulators of Obesity

ENGİN A. B., ENGİN A.

Advances in experimental medicine and biology, cilt.1460, ss.595-627, 2024 (Scopus) identifier identifier

  • Yayın Türü: Makale / Derleme
  • Cilt numarası: 1460
  • Basım Tarihi: 2024
  • Doi Numarası: 10.1007/978-3-031-63657-8_20
  • Dergi Adı: Advances in experimental medicine and biology
  • Derginin Tarandığı İndeksler: Scopus, EMBASE
  • Sayfa Sayıları: ss.595-627
  • Anahtar Kelimeler: Adipocyte-derived microvesicles (ADMs), Adipogenesis, Adiponectin, Cytidine-cytidine-adenosine-adenosine-thymidine (CCAAT)/enhancer-binding protein (C/EBP), Fatty acid binding protein 4 (FABP4), Forkhead box protein O1 (FoxO1), Insulin resistance, Interleukin 1 (IL-1) receptor-associated kinase-1 (IRAK-1), Leptin, Lipid droplets, Lipotoxicity, Micro ribonucleic acid-143 (miR-143), Micro-ribonucleic acid-103 (miR-103), Micro-ribonucleic acid-148a (miR-148a), Micro-ribonucleic acid-155 (miR-155), Micro-ribonucleic acid-221 (miR-221), Micro-ribonucleic acid-223 (miR-223), Micro-ribonucleic acid-33 (miR-33), Micro-ribonucleic acid-34 (miR-34), Micro-ribonucleic acids (miRNAs), Obesity, Oxidized low density lipoprotein (Ox-LDL), Peroxisome proliferator-activated receptor-gamma (PPAR-γ), Silent information regulator 1 (SIRT1), Sterol regulatory element-binding protein (SREBP), Toll-like receptor 4 (TLR4), Triglyceride, Tumor necrosis factor receptor (TNFR)-associated factor 6 (TRAF6), Tumor necrosis factor-alpha (TNF-α), Weight loss
  • Gazi Üniversitesi Adresli: Evet

Özet

In obesity, the process of adipogenesis largely determines the number of adipocytes in body fat depots. Adipogenesis is regulated by several adipocyte-selective micro-ribonucleic acids (miRNAs) and transcription factors that modulate adipocyte proliferation and differentiation. However, some miRNAs block the expression of master regulators of adipogenesis. Since the specific miRNAs display different expressions during adipogenesis, in mature adipocytes and permanent obesity, their use as biomarkers or therapeutic targets is feasible. Upregulated miRNAs in persistent obesity are downregulated during adipogenesis. Moreover, some of the downregulated miRNAs in obese individuals are upregulated in mature adipocytes. Induction of adipocyte stress and hypertrophy leads to the release of adipocyte-derived exosomes (AdEXs) that contain the cargo molecules, miRNAs. miRNAs are important messengers for intercellular communication involved in metabolic responses and have very specific signatures that direct the metabolic activity of target cells. While each miRNA targets multiple messenger RNAs (mRNAs), which may coordinate or antagonize each other's functions, several miRNAs are dysregulated in other tissues during obesity-related comorbidities. Deletion of the miRNA-processing enzyme DICER in pro-opiomelanocortin-expressing cells results in obesity, which is characterized by hyperphagia, increased adiposity, hyperleptinemia, defective glucose metabolism, and alterations in the pituitary-adrenal axis. In recent years, RNA-based therapeutical approaches have entered clinical trials as novel therapies against overweight and its complications. Development of lipid droplets, macrophage accumulation, macrophage polarization, tumor necrosis factor receptor-associated factor 6 activity, lipolysis, lipotoxicity, and insulin resistance are effectively controlled by miRNAs. Thereby, miRNAs as epigenetic regulators are used to determine the new gene transcripts and therapeutic targets.