In summary these findings show that the
In summary, these findings show that the knockdown of tra2 in the Drosophila fat body results in an increased triglyceride phenotype, which could be explained in part by altered splicing of the gene coding for the lipid breakdown enzyme, CPT1. These findings are consistent with previous studies analyzing the SR protein, 9G8, providing support of the hypothesis that these two RNA-binding proteins may be functioning together to control the splicing of lipid metabolic genes and therefore overall lipid homeostasis. The increased triglyceride storage seen with the knockdown of the human tra2 homolog, SFRS10 , has also been consistent with our results suggesting that tra2 and other RNA binding proteins play a highly conserved role in regulating the expression and processing of important metabolic enzymes, many of which have yet to be identified. Together, these results suggest a link between mRNA splicing, sex determination and lipid metabolism and may provide insight into the mechanisms underlying tissue-specific splicing and nutrient storage and the development of obesity.
Acknowledgements Stocks obtained from this (NIH P40OD018537) were used in this study. This work was supported by the National Institutes of Health (grant 1R15NS080155-01A1) and funds from Penn State Berks to JRD.
Introduction Dietary fats play an important role in fish nutrition by providing essential fatty Chlorhexidine digluconate and energy. The lipid-rich diets are used widely because of their protein-sparing effects (Beamish and Medland, 1986; Watanabe, 1982). However, this practice increases fat deposition in cultured fish, compromises fish health, alters metabolic patterns (Lauriano et al., 2016; Rueda-Jasso et al., 2004) and lowers growth and feed efficiency (Du et al., 2006; Nath et al., 2018). Therefore, it is crucial to develop effective feeding strategies to reduce fat accumulation in cultured fish. Different approaches including pharmacologic therapy, surgery and dietary supplements have been used as treatments to reduce overweight and obesity in humans (Colker et al., 1999; Van, 2008; Yamoneka et al., 2015). Dietary supplements offer several advantages over traditional therapy such as low toxic profile, easy accessibility to the general population and wide availability because they are sold over-the-counters (Ríos-Hoyo and Gutiérrez-Salmeán, 2016). Previous studies have investigated the effects of some dietary supplements that are derived from plants on reducing obesity by using in vitro and in vivo methods in various species (Hu et al., 2012; Oben et al., 2008; Park, 2015). African wild mango (Irvingia gabonensis) inhibited adipogenesis in adipocytes by down-regulating the adipogenic transcription factor (peroxisome proliferator-activated receptor gamma (PPAR-γ) (Oben et al., 2008). Raspberry ketone inhibited adipogenesis, adipocyte differentiation and increased transcriptional activities of genes involved in lipolysis and oxidation (Park, 2015). Fucoxanthin, a carotenoid present in edible brown seaweeds, exerted anti-obesity effects by regulating mRNA expression of enzymes related to lipid metabolism in white adipose tissue in diet-induced obesity rats (Hu et al., 2012). A few dietary supplements are also used in aquaculture to modulate lipid metabolism in fish. For example, silibinin from Silybum marianum inhibited lipid accumulation in zebrafish (Suh et al., 2015) and grass carp (Xiao et al., 2017) by reducing adipogenic factors and triglyceride levels. Although these ingredients have effects within preclinical or small-scaled clinical trials, the majority of these trials do not show health-related evidences, food-drug interactions and dose-related body fat reductions (Ríos-Hoyo and Gutiérrez-Salmeán, 2016). 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) cells (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.