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

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.

The effect of different weight loss strategies to treat non-alcoholic fatty liver disease focusing on fibroblast growth factor 21

“…(D) Ratio of subcutaneous flanked fat deposits to body weight ( C,D HFD/HFD: n = 13, HFD/HFD + TM: n = 13, HFD/HFD + TM + TRF: n = 15, HFD/LFD: n = 14, HFD/LFD + TM: n = 15, HFD/LFD + TM + TRF: n = 14; total n = 84). All HFD/LFD groups showed a significant fat loss with p < 0.0001 when compared to all three HFD/HFD groups, respectively [ A–D from Power Guerra et al ( 28 )]. (E) Plasma triglyceride [mg/dL] (HFD/HFD: n = 13, HFD/HFD + TM: n = 13, HFD/HFD + TM + TRF: n = 15, HFD/LFD: n = 14, HFD/LFD + TM: n = 15, HFD/LFD + TM + TRF: n = 14; total n = 84).…”

“…To treat obesity and metabolic disorders, time limited restriction of food is described as a beneficial method ( 29 , 30 ), which was the third intervention parameter, namely, TRF. After the third phase of TM exercise ( Figure 1C ), TRF was introduced to n = 30 mice using the same protocol, as previously described by our group ( 28 ). For the last 3 months, TRF was maintained.…”

“…At the beginning, 90 4-week-old female mice (C57BL/6J) were purchased from Charles River (Sulzfeld, Germany). In compliance with our previous and ongoing investigations, female mice were used for comparability between different studies ( 28 ). All animal experimental work was carried out with permission of the local Animal Research Committee [Landesamt für Landwirtschaft, Lebensmittelsicherheit und Fischerei (LALLF) of the state Mecklenburg-Western Pomerania (LALLF M-V/TSD/7221.3-2-001/18, approved on March 1, 2018)] and by following the ARRIVE guidelines.…”

“…According to randomization, the cages were divided into six groups. In the following 6 months, interventions were carried out as previously published by our group ( 28 ). The first group ( n = 15) remained on an HFD, referred to as “HFD/HFD”.…”

“… Experimental design adapted to Power Guerra et al ( 28 ). (A) Female C57BL/6J mice ( n = 90) were fed for 6 months with high-fat diet (HFD) to establish the model of diet-induced obesity.…”