Fibroblast Growth Factor 21 Reverses Hepatic Steatosis, Increases Energy Expenditure, and Improves Insulin Sensitivity in Diet-Induced Obese Mice

Abstract Context Among cytokines, fibroblast growth factor 21 (FGF21), adiponectin (Adn), and irisin have been considered potential biomarkers for insulin sensitivity (IS). Objective We evaluated whether serum FGF21, Adn, and irisin associate with markers of IS and serum lipids in 12-year-old children. Design, Participants, and Main Outcome Measures This cohort study included 192 12-year-old children (109 girls). Seventy-eight of them had been born appropriate for gestational age (AGA), 70 small for gestational age (SGA), and 44 from preeclamptic pregnancies (PREs) as AGA. Fasting serum FGF21, Adn, irisin, lipids, inflammatory markers, and IS markers were measured. Quantitative insulin sensitivity check index (QUICKI) was calculated. Results The means of serum FGF21, high molecular weight (HMW) Adn, and irisin did not differ between the sexes or between the SGA, AGA, and PRE children. In the whole study population, FGF21 associated positively with irisin and uric acid and negatively with leptin and high-density lipoprotein cholesterol (HDL-C). HMW Adn associated positively with total Adn, HDL-C, leptin, and SHBG. Apart from FGF21, irisin associated positively with insulin, high-sensitivity C-reactive protein, γ-glutamyltransferase, and triglycerides, and negatively with QUICKI, SHBG, and IGF binding protein-1. In multivariate regression analyses, irisin predicted lower IS and HMW Adn predicted higher HDL-C body mass index-independently, whereas FGF21 had no independent contribution to IS or lipid variables. Conclusion In 12-year-old children, serum irisin was associated with markers reflecting reduced IS. HMW Adn predicted HDL-C, whereas FGF21 did not contribute to IS or lipid parameters in multivariate regression analyses.

Download Full-text

Activation of hepatic estrogen receptor-α increases energy expenditure by stimulating the production of fibroblast growth factor 21 in female mice

Molecular Metabolism ◽

10.1016/j.molmet.2019.02.002 ◽

2019 ◽

Vol 22 ◽

pp. 62-70 ◽

Cited By ~ 5

Author(s):

Camille Allard ◽

Fabrice Bonnet ◽

Beibei Xu ◽

Laurel Coons ◽

Diana Albarado ◽

...

Keyword(s):

Estrogen Receptor ◽

Growth Factor ◽

Energy Expenditure ◽

Fibroblast Growth Factor ◽

Estrogen Receptor Α ◽

Fibroblast Growth Factor 21 ◽

Fibroblast Growth ◽

Female Mice

Download Full-text

Naringenin Prevents Obesity, Hepatic Steatosis, and Glucose Intolerance in Male Mice Independent of Fibroblast Growth Factor 21

Endocrinology ◽

10.1210/en.2014-2003 ◽

2015 ◽

Vol 156 (6) ◽

pp. 2087-2102 ◽

Cited By ~ 46

Author(s):

Julia M. Assini ◽

Erin E. Mulvihill ◽

Amy C. Burke ◽

Brian G. Sutherland ◽

Dawn E. Telford ◽

...

Keyword(s):

Fatty Acid ◽

Growth Factor ◽

Glucose Tolerance ◽

Fibroblast Growth Factor ◽

Hepatic Steatosis ◽

Metabolic Adaptation ◽

Fibroblast Growth Factor 21 ◽

Fibroblast Growth ◽

Wild Type ◽

Metabolic Dysregulation

Abstract The molecular mechanisms and metabolic pathways whereby the citrus flavonoid, naringenin, reduces dyslipidemia and improves glucose tolerance were investigated in C57BL6/J wild-type mice and fibroblast growth factor 21 (FGF21) null (Fgf21−/−) mice. FGF21 regulates energy homeostasis and the metabolic adaptation to fasting. One avenue of this regulation is through induction of peroxisome proliferator-activated receptor-γ coactivator-1α (Pgc1a), a regulator of hepatic fatty acid oxidation and ketogenesis. Because naringenin is a potent activator of hepatic FA oxidation, we hypothesized that induction of FGF21 might be an integral part of naringenin's mechanism of action. Furthermore, we predicted that FGF21 deficiency would potentiate high-fat diet (HFD)-induced metabolic dysregulation and compromise metabolic protection by naringenin. The absence of FGF21 exacerbated the response to a HFD. Interestingly, naringenin supplementation to the HFD robustly prevented obesity in both genotypes. Gene expression analysis suggested that naringenin was not primarily targeting fatty acid metabolism in white adipose tissue. Naringenin corrected hepatic triglyceride concentrations and normalized hepatic expression of Pgc1a, Cpt1a, and Srebf1c in both wild-type and Fgf21−/− mice. HFD-fed Fgf21−/− mice displayed greater muscle triglyceride deposition, hyperinsulinemia, and impaired glucose tolerance as compared with wild-type mice, confirming the role of FGF21 in insulin sensitivity; however, naringenin supplementation improved these metabolic parameters in both genotypes. We conclude that FGF21 deficiency exacerbates HFD-induced obesity, hepatic steatosis, and insulin resistance. Furthermore, FGF21 is not required for naringenin to protect mice from HFD-induced metabolic dysregulation. Collectively these studies support the concept that naringenin has potent lipid-lowering effects and may act as an insulin sensitizer in vivo.

Download Full-text

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

Nutrients ◽

10.3390/nu13092916 ◽

2021 ◽

Vol 13 (9) ◽

pp. 2916

Author(s):

Nicole Power Guerra ◽

Alisha Parveen ◽

Daniel Bühler ◽

David Leon Brauer ◽

Luisa Müller ◽

...

Keyword(s):

Growth Factor ◽

Fibroblast Growth Factor ◽

Weight Reduction ◽

Treadmill Exercise ◽

Dietary Change ◽

Fibroblast Growth Factor 21 ◽

Restricted Feeding ◽

Fibroblast Growth ◽

Obese Mice ◽

Potential Biomarker

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.

Download Full-text