Figure 3.

Triacylglycerol (TAG) lipolysis in Drosophila: biochemistry and main regulatory pathways. Mobilization of lipid droplet (LD) fat stores in adipocytes requires TAG hydrolysis by Bmm and Hsl [possibly also by PAPLA1 (Phosphatidic Acid Phospholipase A1)] to fatty acids (FAs) and diacylglycerol (DAG), which become exported to peripheral tissues, or are subjected to further lipolytic cleavage (possibly by Hsl) to release glycerol (G) and FAs. The latter can be catabolized via β-oxidation after activation to FA-CoA by Pdgy. LD coat proteins Plin1 and Plin2 restrict Bmm activity. Plin1 phosphorylation by protein kinase A (Pka) may also promote adipokinetic hormone (Akh)-stimulated TAG mobilization by facilitating the activity of Hsl and/or other currently unknown lipases. Transcription of bmm is under antagonistic control of the Akh pathway during fasting and under the insulin signaling pathway during feeding conditions. Insulin signaling operates via activation of Akt, which represses bmm expression by promoting phosphorylation and cytoplasmic retention of the transcription factor Foxo. In parallel, Akt activates Sik3, which promotes the phosphorylation and cytoplasmic retention of the Foxo-activator HDAC4. Target of rapamycin (Tor) kinase, which is positively regulated by insulin signaling, represses bmm transcript levels by a currently unknown mechanism. The insulin and Akh pathways converge at Sik3, which is suppressed by Pka. Pka, in turn, depends on the cyclic AMP (cAMP) branch of Akh/AkhR (Akh receptor) signaling, which operates via G_s and adenylate cyclase (Ac). Lipolysis also involves the Ca²⁺ branch of AkhR activation (for details see Figure 2 legend and main text). Genetic data support the idea that proteins such as Cam relay the rise in intracellular Ca²⁺, resulting in bmm expression by unknown mechanisms. Proteins shown in faded green with gray lettering are based on homology-based activity predictions and await experimental validation. See main text for definitions of protein name abbreviations. Note the antagonistic action of the lipoanabolic insulin/Tor pathway (in magenta) under feeding vs. the lipocatabolic Akh pathway (in blue) under fasting conditions.