Nile tilapia Oreochromis niloticus is
Nile tilapia (Oreochromis niloticus) is an important species farmed worldwide (Doan et al., 2018). Lipid-rich diets are commonly used in Nile tilapia aquaculture to reduce feed cost, but impair lipid homeostasis (Huang et al., 2016). Therefore, it is important to determine whether forskolin can stimulate lipolysis and reduce fat accumulation in cultured fish where high lipid deposition is undesired. Currently, no research has been conducted to investigate the potential role of forskolin on lipolysis in cultured fish species such as Nile tilapia. The primary objectives of this study were to determine whether 1) forskolin in vitro stimulates lipolysis on Nile tilapia adipocytes (APCs) and hepatocytes (HPCs) and its associated mechanisms; and 2) forskolin (0.5 mg/kg BW and 1.5 mg/kg BW) in vivo has a positive effect on the reduction of fat accumulation in Nile tilapia fed on high fat diet.
Materials and methods
Discussion Lipolysis is an important biochemical process, which breaks down TG into FFAs, for utilization by different body Necrostatin 1 (Young and Zechner, 2013; Zechner et al., 2012). In mammals, ATGL, HSL and MGL are mainly involved in the lipolysis process from TG to diacylglycerols (Seamon et al., 1981), DG to monoacylglycerols (MG), and MG to FFAs, respectively (Chanda et al., 2010; Jenkins et al., 2004; Vaughan et al., 1964; Villena et al., 2004; Zimmermann et al., 2004). Similar to mammals, the three lipases are regulated by the levels of lipids, FFAs, hormones and bioactive ingredients in fish such as grass crap (Ctenopharynogodon idella) (Ji et al., 2012), rainbow trout (Oncorhynchus mykiss) (Kittilson et al., 2011), Japanese flounder (Paralichthys olivaceus) (Khieokhajonkhet et al., 2014), large yellow croaker (Larimichthys crocea) (Wang et al., 2013) as well as Nile tilapia (Ning et al., 2016, Ning et al., 2017; Tian et al., 2013). Although forskolin plays a positive role in reducing fat accumulation in mammals through PKA-dependent activation of HSL and ATGL (Belfrage et al., 1982; Bezaire et al., 2009), little is known about the effects of forskolin on fat metabolism in fish both in vivo and in vitro. In the present study, both doses of 0.5 and 1.5 mg/kg forskolin reduced fat accumulation in vivo by decreasing lipid contents in the whole fish and the liver. Moreover, the HSI and MFI in the fish fed on forskolin were also lower than those in the control. Furthermore, the histological observations confirmed vacuolar degeneration, hyperplasia of hepatic parenchyma and reduction of lipid droplet size in the adipose tissue of the fish fed on forskolin doses. The present study demonstrates that the forskolin can help to decrease fat accumulation in Nile tilapia fed on high fat diet. 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.