Fibroblast Growth Factor 21 as a Potential Biomarker for Improved Locomotion and Olfaction Detection Ability after Weight Reduction in Obese Mice.

Nicole Power Guerra,Rika Bajorat,Angela Kuhla,Kristin Pilz,Luisa Müller,Alisha Parveen,Deborah Janowitz,Brigitte Vollmar,Änne Glass,David Leon Brauer,Daniel Bühler,Martin Witt,Olaf Wolkenhauer

doi:10.3390/nu13092916

Abstract

Obesity is one of the most challenging diseases of the 21st century and is accompanied by behavioural disorders. Exercise, dietary adjustments, or time-restricted feeding are the only successful long-term treatments to date. Fibroblast growth factor 21 (FGF21) plays a key role in dietary regulation, but FGF21 resistance is prevalent in obesity. The aim of this study was to investigate in obese mice whether weight reduction leads to improved behaviour and whether these behavioural changes are associated with decreased plasma FGF21 levels. After establishing a model for diet-induced obesity, mice were subjected to three different interventions for weight reduction, namely dietary change, treadmill exercise, or time-restricted feeding. In this study, we demonstrated that only the combination of dietary change and treadmill exercise affected all parameters leading to a reduction in weight, fat, and FGF21, as well as less anxious behaviour, higher overall activity, and improved olfactory detection abilities. To investigate the interrelationship between FGF21 and behavioural parameters, feature selection algorithms were applied designating FGF21 and body weight as one of five highly weighted features. In conclusion, we concluded from the complementary methods that FGF21 can be considered as a potential biomarker for improved behaviour in obese mice after weight reduction.

Highlights

Obesity is reaching a global epidemic scale and is defined as abnormal or excessive body fat accumulation [1]
The purpose of the study was to investigate in obese mice whether weight reduction leads to improved behaviour and whether these behavioural changes are associated with altered plasma Fibroblast growth factor 21 (FGF21) concentrations
Concerning behavioural analysis, we assumed that time restriction on food (TRF) alone was beneficial [60], but we showed that the combination of dietary change to low-fat diet (LFD) and TM was conducive

Summary

Introduction

Obesity is reaching a global epidemic scale and is defined as abnormal or excessive body fat accumulation [1]. Already in 1989, Kaplan described the “Deadly Quartet” of abdominal obesity, hypertension, hyperglycemia, and hypertriglyceridemia with accompanying low concentrations high-density lipoprotein cholesterol [2]. A promising candidate for reducing plasma concentrations of cholesterol and triglycerides is Fibroblast Growth. Factor (FGF) 21 [3,4]. Obese humans and mice exhibit exceedingly high levels of circulating FGF21 plasma concentrations when compared to lean patients or wild type mice [8]. This evidence sparks the idea of whether FGF21 can be considered as a biomarker in obesity [9,10]

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Conclusion