Nutrition and physical activity affect general health status [
1]. In addition, physical exercise is considered to be the most potent non-pharmacological intervention to manage hepatic alterations. Indeed, regular physical activity beneficially impacts on the risk of hepatic chronic diseases onset and progression. However, research regarding the effects of exercising on chronic liver diseases is relatively recent and not fully explored. Increasing clinical and experimental data focused on liver diseases finding that there is a cross-talk among skeletal muscle, adipose tissue and liver that regulates intrahepatic fat storage [
2,
3]. In this setting, physical activity allows an effective decrease of intrahepatic lipid component, and, despite that evidence is not conclusive, several studies suggest that a vigorous activity might be more effective than moderate activity in improving steatohepatitis [
2‐
5]. On the other hand, evidence regarding the effects of exercise on the risk of hepatocellular carcinoma is scarce; some epidemiological studies indicate a lower risk in patients regularly and vigorously exercising. Among metabolic diseases, obesity is a chronic disease mainly due to excessive fat accumulation that may seriously impair health [
2,
3]. During the last 20 years, obesity has rapidly become a global pandemic health problem, often associated with insulin resistance, diabetes mellitus and dyslipidaemias. In addition, several data demonstrated that concomitant presence of obesity and insulin resistance might be associated with the development of liver diseases [
4]. Indeed, visceral fat mass is a predictor not only of hyperinsulinaemia and insulin resistance but also of hepatic steatosis [
5]. Furthermore, insulin is involved in the regulation of liver free fatty acids (FFA) metabolism and can inhibit hepatic mitochondrial beta-oxidation of FFA while, on the other hand, FFA accumulation in the liver may influence insulin clearance and insulin resistance initiating an unhealthy vicious circle [
6]. For these reasons, a sedentary lifestyle is closely associated to an increased risk of mortality and morbidity for dysmetabolic diseases such as liver diseases and physical activity has an important role in its prevention [
7‐
9]. Indeed, regular exercise promotes favourable muscle construction and metabolic adaptations [
10]. However, it is important to distinguish between regular physical activity and athletic and professional physical activity. Water Polo (WP) is an aquatic team sport characterized by a combination of both aerobic and anaerobic efforts that requires intensive training and a high metabolic demand on the athletes [
11]. Increased energy expenditure, reduced fat depots and promotion of beta-oxidation are at basis of professional sport, such as WP, beneficial effects [
12]. Given the skeletal muscle cross-talking to the adipose tissue and the liver, professional physical activity has numerous beneficial effects not only on metabolic pathways but also on inflammatory processes, regulating cytokines response. In this contest, a key role is played by the pro-inflammatory cytokines, especially tumor necrosis factor-alpha (TNF-α) and IL-6 [
7,
8,
13]. In particular, physical exercise is also able to reverse the imbalance in pro- and anti-inflammatory cytokines, phenomenon at the basis of many inflammatory processes, and to contribute to an overall decline of systemic inflammation [
14,
15]. Several studies, dealing with the association between exercise and inflammation, affirm that physical activity has an anti-inflammatory effect in various pathological and physiological states characterized by low-grade inflammation, such as ageing, metabolic disease, obesity, etc. [
16‐
18]. The anti-inflammatory response induced by physical activity is mediated by the muscle endocrine functions; indeed, during contraction, muscle-derived cytokines, named myokines, are released to regulate both muscle metabolism [
19]. Literature data report that circulating levels of anti-inflammatory cytokines rise and those of the pro-inflammatory adipokines such as tumor necrosis factor alpha (TNFα Interferon gamma INFγ and interleukin (IL)-2 decrease as a result of the regular and moderate physical activity [
16]. Indeed, the pattern of cytokines induced by physical activity is typically anti-inflammatory, with a marked increase in serum levels of several cytokines, such as IL-10, IL-4, and IL-6 [
20‐
22]. Furthermore, the release of IL6 after intense physical exercise as in athletes is reported to create an anti-inflammatory environment [
13,
23,
24].
In this scenario, this study investigated the effects of sera from professional, amateur, inactive and obese subjects on hepatic cells. To this aim, we treated the hepatoma cell line, Hep G2, to find out if sera from different trained subjects could induce a different biological response. In particular, we aimed at clarifying if the treatment with the above-mentioned sera affects cell viability and/or the activation status of AMPKα and ACC, two proteins involved in different molecular pathways linked to metabolism [
25,
26]. Considering that our data show that the treatment with Water Polo player’s sera induces relevant effects on AMPKα and ACC, we analysed the serum cytokine levels (IL-2, IL-4, IL-6, IL-8, IL-10, TNF-α, GM-CSF and IFN γ in these professional athletes’ respect to control subjects.