Defining "FGF21 Resistance" during obesity: Controversy, criteria and unresolved questions.

Kathleen R Markan

doi:10.12688/f1000research.14117.1

Kathleen R Markan

Open Access

https://doi.org/10.12688/f1000research.14117.1

Copy DOI

Journal: F1000Research	Publication Date: Mar 7, 2018
Citations: 36	License type: CC BY 4.0

Affiliation: University of Iowa, Fraternal Order of Eagles

Abstract

The term "FGF21 resistance" was first used to describe increased circulating FGF21 levels concomitant to decreased FGF21 receptor complex expression in white adipose tissue of obese mice. Since this initial report, the term has been associated with a wide range of pathological states, including human obesity, in which circulating FGF21 levels are elevated. However, the notion of "FGF21 resistance" has been controversial partly due to difficulty in delineating the mechanisms underlying the physiological versus pharmacological effects of FGF21. Here, key aspects of the term "FGF21 resistance" are discussed including; the origin and experimental context surrounding the term "FGF21 resistance", new criteria for evaluating FGF21 sensitivity in vivo and finally, crucial unresolved questions regarding the function of FGF21 during obesity.

Highlights

The term “Fibroblast Growth Factor 21 (FGF21) resistance” was first used to describe increased circulating FGF21 levels concomitant to decreased FGF21 receptor complex expression in white adipose tissue of obese mice
Fibroblast Growth Factor 21 (FGF21) has pleiotropic metabolic effects including increasing insulin sensitivity and energy expenditure, while decreasing body weight and sugar intake[1,2]. Paradoxical to these beneficial metabolic effects, circulating FGF21 is increased during obesity potentially suggesting a state of “FGF21 resistance”[3]
“FGF21 resistance” was first used to describe decreased expression of the FGF21 receptor complex in epididymal white adipose tissue, increased plasma FGF21, blunted ERK phosphorylation, and attenuated reduction in plasma glucose following low dose administration of FGF21 that occurred in obese mice[3]

Summary

Introduction

The term “FGF21 resistance” was first used to describe increased circulating FGF21 levels concomitant to decreased FGF21 receptor complex expression in white adipose tissue of obese mice. Fibroblast Growth Factor 21 (FGF21) has pleiotropic metabolic effects including increasing insulin sensitivity and energy expenditure, while decreasing body weight and sugar intake[1,2]. Paradoxical to these beneficial metabolic effects, circulating FGF21 is increased during obesity potentially suggesting a state of “FGF21 resistance”[3].

Results

Conclusion