Hemolymph Sugar Homeostasis and Starvation-Induced Hyperactivity Affected by Genetic Manipulations of the Adipokinetic Hormone-Encoding Gene in Drosophila melanogaster

Abstract

Adipokinetic hormones (AKHs) are metabolic neuropeptides, mediating mobilization of energy substrates from the fat body in many insects. In delving into the roles of the Drosophila Akh (dAkh) gene, its developmental expression patterns were examined and the physiological functions of the AKH-producing neurons were investigated using animals devoid of AKH neurons and ones with ectopically expressing dAkh. The dAkh gene is expressed exclusively in the corpora cardiaca from late embryos to adult stages. Projections emanating from the AKH neurons indicated that AKH has multiple target tissues as follows: the prothoracic gland and aorta in the larva and the crop and brain in the adult. Studies using transgenic manipulations of the dAkh gene demonstrated that AKH induced both hypertrehalosemia and hyperlipemia. Starved wild-type flies displayed prolonged hyperactivity prior to death; this novel behavioral pattern could be associated with food-searching activities in response to starvation. In contrast, flies devoid of AKH neurons not only lacked this type of hyperactivity, but also displayed strong resistance to starvationinduced death. From these findings, we propose another role for AKH in the regulation of starvationinduced foraging behavior.

Energy Homeostasis Control in Drosophila Adipokinetic Hormone Mutants

“…In Drosophila, CC cell ablation suppresses this hyperactivity (Lee and Park 2004), consistent with the view that this behavior requires Akh gene products or other CC cell-produced factors. On the contrary, locomotion of AkhR mutants under starvation was described as identical to controls (Bharucha et al 2008).…”

“…Our data show that unlike its mammalian homolog, AKH does not affect the number of CC cells. Nevertheless, CC cell numbers appear to be subject to environmental or genetic variation, as our study detected more adult CC cells (16 6 0.15 SEM) than was described previously using the same technical approach (13 6 0.6 SEM) (Lee and Park 2004).Regulation of the circulating AKH titer at the level of secretory activity of CC cells under energy-demanding conditions has been linked to the AMPK pathway (Braco et al 2012). However, a role of AKH in AMPK activation, which would establish an autoregulatory loop, has not been addressed.…”

“…In contrast, the role of AKH in circulating sugars in adults was not addressed previously. In larva, however, CC cell ablation was shown to cause hypoglycemia (Kim and Rulifson 2004;Lee and Park 2004;Isabel et al 2005). We were not able to detect any significant differences in the free sugars when analyzing whole body samples; however, when hemolymph samples were analyzed, we observed significant hypoglycemia in Akh A , Akh AP , and AkhR 1 mutants.…”

“…Adipokinetic hormone was described to act hypertrehalosaemic in several insect species including Drosophila larvae (Kim and Rulifson 2004;Lee and Park 2004). Thus, we hypothesized that the loss of AKH function might result in impaired glycogen mobilization, and consequently in higher body glycogen levels.…”

“…Altogether, deficiencies of AKH signaling or APRP had no effect on the lipid content at any tested developmental stage or on the storage lipid mobilization during metamorphosis (see statistical analyzes in Figure 4A). Adipokinetic hormone was described to act hypertrehalosaemic in several insect species including Drosophila larvae (Kim and Rulifson 2004;Lee and Park 2004). Thus, we hypothesized that the loss of AKH function might result in impaired glycogen mobilization, and consequently in higher body glycogen levels.…”