To the best of our knowledge the present study

To the best of our knowledge, the present study was the first to show that forskolin can stimulate lipolysis in APCs and HPCs in fish. Although HSL gene expression was not increased significantly by forskolin in APCs and HPCs for the in vitro experiments, the dietary supplementation of forskolin up-regulated significantly HSL mRNA expression in the Nile tilapia adipose tissues in the in vivo experiments. Moreover, the adipose tissue seems to be more sensitive to forskolin than the liver tissue because ATGL, HSL and MGL mRNA expressions were all increased in the adipose tissue but not in the liver tissue. This may be due to the fact that, the adipose rather than the liver is the main tissue for lipid deposition and lipolysis (Ahmadian et al., 2007). These results indicate that, similar to mammals, forskolin can stimulate lipolysis by up-regulating the mRNA expression of PKAR I, II and PKAC as well as the lipases genes such as ATGL, HSL and MGL. Presently, there is no evidence which shows toxicity of forskolin in animal trials. In a previous study, the root extract of Coleus forskohlii induced hepatotoxicity in mice by unidentified constituents in the plant rather than by the forskolin itself (Virgona et al., 2013). Similarly, in the present study, forskolin also did not affect fish weight gain and protein content, which are the important variables to evaluate fish growth and nutritional status. These results suggest, forskolin has little influence on Nile tilapia growth, although more studies are still needed to evaluate the health effects of forskolin on fish. Lipolysis and fatty Fmoc-Ala-OH oxidation are two important mechanisms involved in fat reduction. Over stimulation of lipolysis increases the level of FFAs in the serum and causes metabolic perturbation (Koutsari and Jensen, 2006). A large inflow of FFAs to the mitochondria may lead to mitochondrial membrane permeabilization and cell death (Engin, 2017). Lipotoxicity occurs due to unbalanced lipolysis (Bülow et al., 2017) or impaired β-oxidation (Haffar et al., 2015). Therefore, Langin (2006) suggested that the control of molecules that stimulate lipolysis and fatty acid (FA) oxidation release could be a useful approach to decrease fat accumulation. Forskolin seems to be an efficient supplement compared to other weight management compounds like l-carnitine and fenofibrate have been used, which showed different degrees of effectiveness in lipid metabolism. Using l-carnitine, Li et al. (2017) showed enhanced mitochondrial β-oxidation activities and decreased lipid in liver and muscle tissues of treated zebrafish. However, l-carnitine application showed no effects on lipid metabolism in some fish species like African catfish (Torreele et al., 1993), hybrid tilapia (Yang et al., 2009) and hybrid striped bass (Twibell and Brown, 2000) or even caused negative effects on lipid metabolism in red sea bream (Chatzifotis et al., 1995) and rainbow trout (Selcuk et al., 2010). By using fenofibrate, Ning et al. (2016) indicated increased PPARα mRNA expression and decreased hepatic TG in Nile tilapia. Their following work also showed decreased hepatic and plasma TG in Nile tilapia fed with on fat diet supplemented with fenofibrate (Ning et al., 2017). However, these authors pointed out that dietary fenofibrate did not change mesenteric fat quantity and TG concentrations in muscle and adipose tissues.