A role for triglyceride lipase brummer in the regulation of sex differences in Drosophila fat storage and breakdown

Abstract

Triglycerides are the major form of stored fat in all animals. One important determinant of whole-body fat storage is whether an animal is male or female. Here, we use Drosophila, an established model for studies on triglyceride metabolism, to gain insight into the genes and physiological mechanisms that contribute to sex differences in fat storage. Our analysis of triglyceride storage and breakdown in both sexes identified a role for triglyceride lipase brummer (bmm) in the regulation of sex differences in triglyceride homeostasis. Normally, male flies have higher levels of bmm mRNA both under normal culture conditions and in response to starvation, a lipolytic stimulus. We find that loss of bmm largely eliminates the sex difference in triglyceride storage and abolishes the sex difference in triglyceride breakdown via strongly male-biased effects. Although we show that bmm function in the fat body affects whole-body triglyceride levels in both sexes, in males, we identify an additional role for bmm function in the somatic cells of the gonad and in neurons in the regulation of whole-body triglyceride homeostasis. Furthermore, we demonstrate that lipid droplets are normally present in both the somatic cells of the male gonad and in neurons, revealing a previously unrecognized role for bmm function, and possibly lipid droplets, in these cell types in the regulation of whole-body triglyceride homeostasis. Taken together, our data reveal a role for bmm function in the somatic cells of the gonad and in neurons in the regulation of male-female differences in fat storage and breakdown and identify bmm as a link between the regulation of triglyceride homeostasis and biological sex.

Early-life hypoxia alters adult physiology and reduces stress resistance and lifespan in Drosophila

“…We focused on looking at TAG since proper mobilization of lipid stores has been shown to be essential for starvation tolerance in Drosophila. Both NORMOXIC males and females showed a decrease in total TAG levels following starvation, with this effect being more pronounced in males, a previously reported result that is consistent with mobilization of lipid stores in nutrient deprived conditions (Gronke et al, 2007; Wat et al, 2020). In contrast, HYPOXIC animals showed a sexually dimorphic response to starvation.…”

“…However, we also found that both male and female HYPOXIC animals showed a defect in lipid mobilization upon starvation, and that these effects were sexually dimorphic. In the case of males, the NORMOXIC control group showed a reduction in total TAG levels following starvation - a phenotype that has been reported before and is consistent with mobilization of lipid stores to support survival during nutrient starvation (Gronke et al, 2007; Palanker et al, 2009; Wat et al, 2020). However, we found that this decreases in TAG levels was significantly exacerbated in the HYPOXIC group, who showed an almost complete depletion of their lipid stores.…”

“…Numerous studies have shown that the storage and mobilization of nutrient stores, particularly lipids, are essential for Drosophila to tolerate starvation stress and to maintain normal lifespan (Heier and Kuhnlein, 2018). This mobilization of nutrient stores is required to allow proper fuelling of key metabolic processes required to allow animals to survive in the absence of food (Gronke et al, 2007; Palanker et al, 2009; Molaei et al, 2019; Wat et al, 2020). In this context, we identified alterations in both lipid storage and mobilization in Drosophila adult previously exposed to hypoxia as larvae.…”

“…One possibility suggested by a recent study involves a sexually dimorphic regulation of the lipase, brummer. Wat et al showed that adult male flies showed higher starvation-mediated induction of brummer compared to females, and, as a result they showed faster lipid depletion and decreased starvation survival (Wat et al, 2020). In our case, it is possible that larval hypoxia may subsequently lead to male:female differences in brummer regulation that could explain why our HYPOXIC flies showed both sexual dimorphic changes in lipid mobilization and overall reduced starvation survival.…”

Sequestration to lipid droplets promotes histone availability by preventing turnover of excess histones

“…Recent discoveries indeed suggest important, but largely uncharacterized roles for LDs in this cell type (Pennetta & Welte, 2018;Wat et al, 2020).…”