Faculty of Pharmacy, Department of Toxicology, Gazi University, Hipodrom, Ankara, Turkey.
Faculty of Medicine, Department of General Surgery, Gazi University, Besevler, Ankara, Turkey.
Adv Exp Med Biol. 2024;1460:595-627. doi: 10.1007/978-3-031-63657-8_20.
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.
在肥胖症中，脂肪生成过程在很大程度上决定了体脂肪库中脂肪细胞的数量。脂肪生成受几种脂肪细胞选择性 microRNA（miRNA）和转录因子的调节，这些因子调节脂肪细胞的增殖和分化。然而，一些 miRNA 会阻断脂肪生成的主调控因子的表达。由于特定的 miRNA 在脂肪生成过程中、在成熟脂肪细胞和永久性肥胖中显示出不同的表达，因此它们可用作生物标志物或治疗靶点。在持续性肥胖中上调的 miRNA 在脂肪生成过程中下调。此外，肥胖个体中下调的一些 miRNA 在成熟脂肪细胞中上调。脂肪细胞应激和肥大的诱导导致脂肪细胞衍生的外泌体（AdEX）的释放，其中包含货物分子 miRNA。miRNA 是参与代谢反应的细胞间通讯的重要信使，具有非常特定的特征，可指导靶细胞的代谢活性。虽然每个 miRNA 靶向多个信使 RNA（mRNA），这些 mRNA 可能相互协调或拮抗，但在肥胖相关合并症期间，其他组织中的几个 miRNA 失调。在表达前阿黑皮素原的细胞中缺失 miRNA 加工酶 DICER 会导致肥胖，其特征是暴食、脂肪量增加、瘦素血症、葡萄糖代谢缺陷和垂体肾上腺轴改变。近年来，基于 RNA 的治疗方法已作为超重及其并发症的新型治疗方法进入临床试验。miRNA 可有效控制脂滴形成、巨噬细胞积累、巨噬细胞极化、肿瘤坏死因子受体相关因子 6 活性、脂肪分解、脂毒性和胰岛素抵抗。因此，作为表观遗传调节剂的 miRNA 用于确定新的基因转录物和治疗靶点。
