RESUMEN
Long non-coding RNAs (lncRNAs) are single-stranded RNA biomolecules with a length of >200 nt, and they are currently considered to be master regulators of many pathological processes. Recent publications have shown that lncRNAs play important roles in the pathogenesis and progression of insulin resistance (IR) and glucose homeostasis by regulating inflammatory and lipogenic processes. lncRNAs regulate gene expression by binding to other non-coding RNAs, mRNAs, proteins, and DNA. In recent years, several mechanisms have been reported to explain the key roles of lncRNAs in the development of IR, including metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), imprinted maternal-ly expressed transcript (H19), maternally expressed gene 3 (MEG3), myocardial infarction-associated transcript (MIAT), and steroid receptor RNA activator (SRA), HOX transcript antisense RNA (HOTAIR), and downregulated Expression-Related Hexose/Glucose Transport Enhancer (DREH). LncRNAs participate in the regulation of lipid and carbohydrate metabolism, the inflammatory process, and oxidative stress through different pathways, such as cyclic adenosine monophosphate/protein kinase A (cAMP/PKA), phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT), polypyrimidine tract-binding protein 1/element-binding transcription factor 1c (PTBP1/SREBP-1c), AKT/nitric oxide synthase (eNOS), AKT/forkhead box O1 (FoxO1), and tumor necrosis factor-alpha (TNF-α)/c-Jun-N-terminal kinases (JNK). On the other hand, the mechanisms linked to the molecular, cellular, and biochemical actions of lncRNAs vary according to the tissue, biological species, and the severity of IR. Therefore, it is essential to elucidate the role of lncRNAs in the insulin signaling pathway and glucose and lipid metabolism. This review analyzes the function and molecular mechanisms of lncRNAs involved in the development of IR.
Asunto(s)
Resistencia a la Insulina/genética , ARN Largo no Codificante/genética , Animales , Glucosa/genética , Humanos , Insulina/genética , Metabolismo de los Lípidos/genética , Transducción de Señal/genéticaRESUMEN
Introduction: Cardiometabolic diseases are a global public health problem, with significant increases in their prevalence. Different epigenetic factors involved in the progression of metabolic alterations have been described, such as long non-coding RNAs (lncRNAs). H19 is a multifunctional lncRNA expressed from the maternal allele, with low expression after birth, except in the skeletal muscle and heart. Recent studies have linked its dysregulation to alterations in cell metabolism.Areas covered: H19 plays a role in the pathogenesis of coronary artery disease, nonalcoholic fatty liver disease, hepatic and renal fibrosis, insulin resistance, type 2 diabetes, and inflammation. H19 acts mainly as a competitive endogenous RNA of molecules involved in pathways that regulate cell metabolism. In this review, we analyzed the dysregulation of H19 in cardiometabolic diseases and its relationship with molecular alterations in different signaling pathways.Expert opinion: The association of H19 with the development of cardiometabolic diseases, indicates that H19 could be a therapeutic target and prognostic biomarker for these diseases. Controversies have been reported regarding the expression of H19 in some metabolic diseases, therefore, it is necessary to continue research to clarify its pathogenic effect in different organs.