成纤维生长因子21在代谢紊乱中的潜在主调控作用
Fibroblast growth factor 21 as a potential master regulator in metabolic disorders
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影响因子:3.1
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
DOI:
10.1152/ajpendo.00244.2022
摘要
FGF21是一种调节关键代谢过程的内分泌激素，能诱导葡萄糖转运蛋白的合成，从而增加脂肪细胞中的葡萄糖吸收。它在多种代谢活跃的器官和组织中表达。作为过氧化物酶体增殖物激活受体（PPAR）的直接下调基因，FGF21在调节葡萄糖稳态方面具有重要作用，参与调控葡萄糖和脂质的活性。已有研究尝试理解与FSGF21相关的多方面特性，包括受体结合、基因组连接图，以及调控FGF21上调的基因和其通过直接或间接途径下调在多种代谢途径中关键基因的机制。此外，关于特定基因的调控分析涉及微RNA（miRNA）、长链非编码RNA（lncRNA）以及单核苷酸多态性（SNPs），这些因素是细胞失调和多种代谢疾病及癌症发病机制的常见原因。FGF21与PPARγ之间的特异性蛋白-蛋白相互作用及交叉调控揭示了它们在代谢紊乱相关调控活动中的联合作用。其作为多种心血管和代谢疾病的潜在生物标志物的潜力也受到关注。本研究旨在强调FGF21在过表达和抑制级联反应后，表现出多效性作用，包括通过饮食引发肥胖、促使脂肪细胞吸收葡萄糖以及在糖尿病模型中降低甘油三酯和血糖水平的机制，显示其在多种代谢及心血管疾病治疗中的潜在价值。
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.