Acute Exercise Induces FGF21 Expression in Mice and in Healthy Humans

Kook Hwan Kim,Seong Hun Kim,Jeong-Beom Lee,Myung-Shik Lee,Hun-Mo Yang,Young-Ki Min,Cedric Moro

doi:10.1371/journal.pone.0063517

Abstract

Fibroblast growth factor 21 (FGF21) plays an important role in the regulation of energy homeostasis during starvation and has an excellent therapeutic potential for the treatment of type 2 diabetes in rodents and monkeys. Acute exercise affects glucose and lipid metabolism by increasing glucose uptake and lipolysis. However, it is not known whether acute exercise affects FGF21 expression. Here, we showed that serum FGF21 level is increased in mice after a single bout of acute exercise, and that this is accompanied by increased serum levels of free fatty acid, glycerol and ketone body. FGF21 gene expression was induced in the liver but not in skeletal muscle and white adipose tissue of mice after acute exercise, and further, the gene expression levels of hepatic peroxisome proliferator-activated receptor α (PPARα) and activating transcription factor 4 (ATF4) were also increased. In addition, we observed increased FGF21 level in serum of healthy male volunteers performing a treadmill run at 50 or 80% VO2max. These results suggest that FGF21 may also be associated with exercise-induced lipolysis in addition to increased catecholamines and reduced insulin.

Highlights

Fibroblast growth factor 21 (FGF21) is an endocrine hormone that belongs to the FGF family and is mainly expressed in the liver [1]
free fatty acid (FFA) released from the adipose tissue by lipolysis are employed as an energy source through fatty acid oxidation in many peripheral tissues or as substrate for ketogenesis in the liver
Acute exercise promotes lipolysis of adipose tissue, and subsequently released FFAs are utilized as a major fuel for ATP production in peripheral tissues such as skeletal muscle and the liver

Summary

Introduction

Fibroblast growth factor 21 (FGF21) is an endocrine hormone that belongs to the FGF family and is mainly expressed in the liver [1]. Many reports showed that skeletal muscle produces and releases a variety of cytokines after exercise (referred to myokines), which act as paracrine or endocrine factors, and modulate beneficial effects on metabolic and physiological responses to exercise [13]. These myokines include interleukine-6 (IL-6), IL-15, brain-derived neurotrophic factor (BDNF) and leukemia inhibitory factor (LIF) [14,15,16,17]. It was recently shown that FGF21 expression is increased in skeletal muscle of muscle-specific Akt transgenic mice which exhibit protection from high-fat diet (HFD)induced obesity and insulin resistance, indicating the beneficial effects of FGF21 as a myokine in metabolic disorders [2]. We recently showed that increased FGF21 from skeletal muscle with autophagy deficiency contributes to an improvement of obesity and insulin resistance in muscle-specific Atg7-deficient mice fed HFD compared to control mice fed HFD [18]

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