Fibroblast growth factor 21 as a potential master regulator in metabolic disorders

Author:

Velingkar Aayushi1,Vuree Sugunakar2ORCID,Prabhakar Pranav Kumar3,Kalashikam Rajender Rao4,Banerjee Aparna5,Kondeti Suresh6ORCID

Affiliation:

1. Department of Biotechnology and Bioinformatics, School of Biosciences and Bioengineering, Lovely Professional University, Phagwara, India

2. MNR Foundation for Research & Innovation, MNR Medical College & Hospital, MNR University, Sangareddy, India

3. Division of Research and Development, Department of Research Impact & Outcome, Lovely Professional University, Phagwara, India

4. Molecular Genetics Lab, Animal Facility, ICMR-National Institute of Nutrition, Hyderabad, India

5. Centro de investigación de Estudios Avanzados Del Maule (CIEAM), Vicerrectoría de Investigación Y Posgrado, Universidad Católica Del Maule, Talca, Chile

6. Multi-disciplinary Research Unit, Nizam’s Institute of Medical Sciences, Panjagutta, India

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.

Funder

NA

Publisher

American Physiological Society

Subject

Physiology (medical),Physiology,Endocrinology, Diabetes and Metabolism

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