The Drosophila model to interrogate triacylglycerol biology

Sex determination genetransformerregulates the male-female difference inDrosophilafat storage via the adipokinetic hormone pathway

“…While the mechanisms underlying the regulation of intracellular fat breakdown by Akh have been well-documented (Bharucha et al, 2008; Gáliková et al, 2015; Grönke et al, 2007; Heier and Kühnlein, 2018; Heier et al, 2021; Kubrak et al, 2020; Lee and Park, 2004; Lehmann, 2018; Scopelliti et al, 2019; Zhao and Karpac, 2017), our findings reveal a new role for Akh in regulating the sex difference in fat storage. Notably, this Akh-mediated regulation of the male-female difference in fat storage operates in a parallel pathway to the previously described sex-specific role of triglyceride lipase bmm (Figure 4 - figure supplement 2A,B) (Wat et al, 2020).…”

“…These findings support a model in which it is Akh production by the APCs that plays a role in regulating the male-female difference in fat storage. While Akh is a known regulator of whole-body fat metabolism (Heier and Kühnlein, 2018;Heier et al, 2021), our findings reveal a new role for Akh in regulating the sex difference in fat storage. Notably, this Akh-mediated regulation of the male-female difference in fat storage operates in a parallel pathway to the previously described sex-specific role of triglyceride lipase bmm (Figure 4 -figure supplement 2A,B) (Wat et al, 2020).…”

“…In contrast, triglyceride levels in 5-day-old Akh-GAL4>UAS-rpr females were not significantly different from Akh-GAL4>+ and +>UAS-rpr control females (Figure 4 - figure supplement 1A). This suggests that the male bias in Akh pathway activity normally contributes to the sex difference in fat storage by limiting triglyceride accumulation in males via the established intracellular signaling cascade known to regulate lipid droplet breakdown (Arrese et al, 2008; Heier and Kühnlein, 2018; Heier et al, 2021; Kühnlein, 2012; Patel et al, 2005). Importantly, we reproduced the male- biased effects on fat storage in flies carrying mutant Akh and AkhR alleles ( Akh A and AkhR 1 , respectively) (Figure 4B,C; Figure 4 - figure supplement 1B,C), and show that APC-specific knockdown of Lst had no effect on fat storage in either sex (Figure 4 - figure supplement 1D,E).…”

“…In contrast, triglyceride levels in 5-day-old Akh-GAL4>UAS-rpr females were not significantly different from Akh-GAL4>+ and +>UAS-rpr control females (Figure 4 -figure supplement 1A). This suggests that the male bias in Akh pathway activity normally contributes to the sex difference in fat storage by limiting triglyceride accumulation in males via the established intracellular signaling cascade known to regulate lipid droplet breakdown (Arrese et al, 2008;Heier and Kühnlein, 2018;Heier et al, 2021;Kühnlein, 2012;Patel et al, 2005). Importantly, we reproduced the malebiased effects on fat storage in flies carrying mutant Akh and AkhR alleles ( While the mechanisms underlying the regulation of intracellular fat breakdown by Akh have been well-documented (Bharucha et al, 2008;Gáliková et al, 2015;Grönke et al, 2007;Heier and Kühnlein, 2018;Heier et al, 2021;Kubrak et al, 2020;Lee and Park, 2004;Lehmann, 2018;Scopelliti et al, 2019;Zhao and Karpac, 2017), our findings reveal a new role for Akh in regulating the sex difference in fat storage.…”

“…Clues into potential mechanisms underlying the sex difference in fat storage have emerged from studies on the regulation of triglyceride metabolism in Drosophila . While many pathways impact whole-body triglyceride levels (Ballard et al, 2010; Bjedov et al, 2010; Broughton et al, 2005; Choi et al, 2015; DiAngelo and Birnbaum, 2009; Francis et al, 2010; Ghosh and O’Connor, 2014; Grönke et al, 2010; Heier and Kühnlein, 2018; Heier et al, 2021; Hentze et al, 2015; Kamareddine et al, 2018; Kang et al, 2017; Kubrak et al, 2020; Lee et al, 2019; Lehmann, 2018; Luong et al, 2006; Rajan and Perrimon, 2012; Roth et al, 2018; Scopelliti et al, 2019; Sieber and Spradling, 2015; Song et al, 2014, 2017; Suzawa et al, 2019; Teleman et al, 2005; Texada et al, 2019), the Adipokinetic hormone (Akh; FBgn0004552) pathway plays a central role in regulating whole-body fat storage and breakdown (Heier and Kühnlein, 2018; Heier et al, 2021; Lehmann, 2018). Akh is synthesized as a preprohormone in the Akh- producing cells (APCs), and is subsequently cleaved by proprotein convertases to produce active Akh (Lee and Park, 2004; Noyes et al, 1995; Predel et al, 2004; Wegener et al, 2006).…”