# The Effect of Hot Water Extract of Tilapia on Exercise Capacity in Mice
## 1 Introduction  
Fatigue, a common term describing a gradual decline in energy and activity, is a highly exhausted feeling that can lead to a variety of physical and emotional discomforts, such as reduced concentration, slowed reflexes and responses, or feeling abnormally sleep [1, 2]. Fatigue has become an important global issue since it affects approximately 20% of the population in several developed countries [3]. Forms of physical fatigue can be classified as either central or peripheral [4, 5]. The former occurs in the central nervous system, and relates to key components in muscle that increase during exercise, such as hydrogen ions, potassium ions, phosphates, prostaglandandins, etc. These components bind to specific fatigue receptors in the muscle, then transmit signals to the brain through the sensory nerves [6]. The decline in blood glucose levels with central fatigue limits the glucoseutilization of neurons in the brain, and changes in plasma amino acid concentration have also been identified [7]. Peripheral fatigue is mainly caused by the depletion of energy stores (e.g., glycogen or phosphocreatine in the liver and muscles) and the accumulation of excess metabolites during physical activity (e.g., lactate in muscle) [8]. All phenomena of central and peripheral fatigue, as described above, are suitable biochemical indicators for assessing the degree of fatigue. The formation of oxidative stress in active skeletal muscle and the liver is also involved in exercise-induced fatigue [9]. Oxidative stress activates the inflammatory response via enhanced expression of pro-inflammatory cytokines like tumor necrosis factor-\(\alpha\) (TNF-\(\alpha\)) [10] and causes the depletion of the antioxidant glutathione (GSH) [11].  
Nowadays, fatigue is a common issue for most people, and it results in negative effects such as inattention and mental paralysis at work, which leads to a decline in efficiency. Moreover, fatigue is a health-related state that is highly correlated with a lower quality of life, and which can cause fatigue syndrome and even physical and emotional discomfort [12]. Therefore, the search for natural food sources to develop functional supplements that improve athletic capacity and boost fatigue recovery has become the focus of research [13]. Reports have shown that several active components in nature possess an anti-fatigue activity, such as proanthocyanidin [14], flavonoids [15], terpenoids [16], nucleotides [17], peptides [18], polysaccharides [19], and amino acids [7; 20]. Recently, extracts and components from aquatic products, such as leather carp (_Cypritus carpio_) and grass carp (_Ctenopharyngodon idellus_), have been shown to enhance the exercise performance of mice during swimming endurance tests [21; 22].  
Tilapia (_Orechromis mossambicus_), a tropical fish species of Cichlidae originating in Africa, is now the third most globally farmed fish, after carp and salmon, with a worldwide production of 4,800,000 tons in 2013 [23]. Tilapia was first introduced to Taiwan in 1944, and then improved through breeding before being renamed Wu-Kuo Yu (fish) in Chinese, also known as Taiwanese tilapia [24]. Tilapia has become one of the major freshwater aquaculture species in Taiwan due to its rapid growth, stable price, and the availability of mature processing technology. Furthermore, because of its high protein and mineral levels and relatively low fat content, tilapia is an aquatic product with high nutritional value. In the present study, we further investigate the effects of a hot water extract of tilapia (HWET) on exercise-induced fatigue in mice using a swimming endurance test.