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  • Forskolin is a labdane diterpene produced from the

    2020-08-05

    Forskolin is a labdane diterpene produced from the root of Coleus forskohlii (Bhat et al., 1977). Its extract has been recorded in Ayurveda medicine since ancient times and its medicinal value has been studied since early-1980s (Bristow et al., 1984; Kavitha et al., 2010). Early studies have suggested that forskolin is a potential agent for management and treatment of obesity. Forskolin promoted lipolysis by regulating the production of cyclic adenosine monophosphate levels in membranes, cells, or tissues (Insel and Ostrom, 2003) through activation of cAMP-dependent protein kinase (PKA) and hormone-sensitive lipase (HSL) (Belfrage et al., 1982). Previous studies have also shown that, forskolin regulates lipolysis by stimulating perilipin A in mice adipocytes (Miyoshi et al., 2006) and adipose triglyceride lipase (ATGL) in human multipotent adipose-derived stem (hMADS) PF-5274857 sale (Bezaire et al., 2009). In small-scaled clinical trials, the in vivo use of forskolin supplements for 12 weeks twice a day decreased significantly the body fat in obese men (Godard et al., 2005). Its supplement has also been shown to increase significantly the high-density lipoprotein-cholesterol together with reduction of waist and hip circumference in humans (Loftus et al., 2015). However, compared to the knowledge on the use of forskolin for regulation of lipolysis in mammals, information on its effects in fish is currently unknown. Considering the potential effect of forskolin on reducing fat accumulation, there is a need for further exploration on its physiological role in fat reduction and the underlying mechanisms in cultured fish. 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
    Results
    Discussion Lipolysis is an important biochemical process, which breaks down TG into FFAs, for utilization by different body cells (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.