成纤维细胞生长因子21作为代谢性疾病中潜在的主要调节剂
Fibroblast growth factor 21 as a potential master regulator in metabolic disorders
影响因子:3.10000
分区:医学2区 / 生理学2区 内分泌学与代谢3区
发表日期:2023 May 01
作者:
Aayushi Velingkar, Sugunakar Vuree, Pranav Kumar Prabhakar, Rajender Rao Kalashikam, Aparna Banerjee, Suresh Kondeti
摘要
FGF21是一种控制关键代谢过程并诱导葡萄糖转运蛋白的合成，导致脂肪细胞中葡萄糖吸收水平升高。它在多个代谢活性器官和组织中表达。 FGF21也是葡萄糖稳态的强大调节剂，它是过氧化物酶体增殖物激活受体（PPAR）的直接下调基因，该基因在调节葡萄糖和脂质的活性中起作用。尝试了解与FGF21相关的各个方面的尝试，包括受体结合和基因组链接图等特性，以及有关FGF21上调起作用的基因的信息，以及它如何直接和间接地下调在各种代谢途径中至关重要的基因。此外，观察到了针对靶向FGF21并改变其功能以及单核苷酸多态性（SNP）的特定基因的各种基因调节分析，这些基因是独特的微RNA和长期非编码RNA，这是细胞失调的常见原因，导致了不同的代谢性疾病和病理疗法。 FGF21和PPARγ之间独特的蛋白质 - 蛋白质相互作用和交叉谈话揭示了它们在代谢障碍相关的调节活性中的综合作用。它作为各种心血管和代谢疾病的有效生物标志物的潜力和独特作用也得到了强调。这项研究试图强调FGF21活性在其过表达和抑制级联反应后的多效性作用，从而导致饮食诱导肥胖，并同时发出脂肪细胞的信号，以吸收葡萄糖并在糖尿病模型中降低甘油三酸酯和降低糖尿病模型（在给药后），以使其对糖尿病的治疗产生较少的治疗。
Abstract
FGF21 is an endocrine hormone that controls key metabolic processes and induces the synthesis of glucose transporters, resulting in increased glucose absorption levels in fat cells. It is expressed in multiple metabolically active organs and tissues. FGF21 is also a powerful regulator of glucose homeostasis as a direct downregulating gene of peroxisome proliferator-activated receptor (PPAR), which plays a role in regulating the activity of glucose and lipids. Attempts were made to understand various aspects related to FGF21, including properties like receptor binding and genomic linkage map, along with the information about the genes that function in the upregulation of FGF21 and how it, directly and indirectly, downregulates the genes that are vital in various metabolic pathways. Furthermore, various gene regulatory analyses on the specific gene concerning unique micro RNAs and long non-coding RNAs that target FGF21 and alter its functioning along with single-nucleotide polymorphisms (SNPs) were observed, that are the common cause of cell dysregulation, leading to different metabolic diseases and pathogenesis of cancer. Unique protein-protein interaction and cross talk between FGF21 and PPARγ shed light on their combined role in metabolic disorder-related regulatory activities. Its potential and unique role as an effective biomarker for various cardiovascular and metabolic disorders have also been highlighted. This study attempts to highlight the pleiotropic role of FGF21 activity following its overexpression and inhibition of cascades that results in the induction of obesity from diet and simultaneously signals adipocytes to absorb glucose and decrease triglyceride and blood sugar levels in diabetic models (after administration), rendering it a promising treatment for several metabolic and cardiovascular disorders.