The obesity‐related Adipokinetic hormone controls feeding and expression of neuropeptide regulators of Drosophila metabolism

Abstract

Homeostasis of circulating and storage energy reserves in mammals is dependent on the antagonistically acting insulin and glucagon signaling. In the model organism Drosophila melanogaster, this function is executed by the insulin‐like peptides and the glucagon‐like Adipokinetic hormone (AKH). Loss of Drosophila AKH results in the adulthood‐specific onset of obesity coupled with hypoglycemia. However, apart from the role of AKH in the lipid mobilization, the physiological and endocrine underpinnings of the AKH deficiency‐triggered obesity are unknown. Here, we investigate the role of AKH in feeding and metabolic rate control, and address the interactions of this hormone with other endocrine regulators of fly metabolism. Via in vivo gain‐ and loss‐of‐function analyses, we show that despite its anti‐obesity effects, AKH is an orexigenic peptide. Moreover, AKH also affects expression of orexigenic factors CCHamide‐2 and neuropeptide F. In addition, AKH regulates metabolic genes like Corazonin, Limostatin, and Insulin‐like peptides (Ilps) 2, 3, 5, and 6. Altogether, our work shows that the Drosophila AKH is a central regulator of energy homeostasis; next to its well‐known role in the control of energy expenditure, this hormone controls also food intake, and expression of other endocrine regulators of fly metabolism. Practical applications: Basic research of the neuroendocrine regulation of metabolism in the fruit fly D. melanogaster has potential applications in both human medicine and insect pest control. The evolutionary conservation of the key metabolic pathways, together with the unprecedented choice of transgenic tools turned the fruit fly into a useful model to study human diseases, including obesity and diabetes. Based on the evolutionary conservation of AKH and glucagon functions, our investigations might provide useful hints regarding the physiological actions, and endocrine interactions of human glucagon, too. In addition, insect neuropeptides are emerging as important targets for the parasite and pest control; understanding of their regulatory networks has thus potential implications also in the development of novel insecticides. Adipokinetic hormone (AKH) is an insect analog of the human hormone glucagon. Our investigations of the roles of this hormone in the model organism Drosophila melanogaster have shown that this anti‐obesity factor is a central regulator of fly metabolism, and controls crucial processes such as feeding, metabolic rate, storage of energy reserves, and expression of regulatory genes from the neuropeptide hormone family, including the fly homologs of human insulin.

Muscle Directs Diurnal Energy Homeostasis through a Myokine-Dependent Hormone Module in Drosophila

“…Our results suggest that AKH, in the absence of starvation, may also have a significant role regulating systemic lipid synthesis, and subsequently fat storage and circulating lipid levels, in response to diurnal changes in activity and feeding. These results are supported by recent work in Drosophila showing that ectopically increasing AKH levels leads to lean animals without a corresponding increase in metabolic rate [57]. Another recent study provides additional evidence that diet and/or nutrient sensing in the gut can direct AKH signaling activity in the fat body, and subsequently affect circulating carbohydrates [58].…”

Spastic paraplegia-linked phospholipase PAPLA1 is necessary for development, reproduction, and energy metabolism in Drosophila

“…Nevertheless, da- GS-driven overexpression of wild type form of PAPLA1 decreased fat content (Fig. 5d), similar to overexpression of Akh 32 or bmm 29. Yet the low fat content triggered by this manipulation might have been contributed also by the toxicity of the manipulation, as around 50% of flies died prior to the analysis.…”

“…S1), and induced their expression in adult flies using the ubiquitous daughterless -GeneSwitch ( da -GS) driver31. Adult-specific PAPLA1 knockdown reduced fat storage, opposite to the obese phenotype caused by the corresponding manipulation of the lipid catabolism genes AkhR and bmm 32 (Fig. 5c).…”

“…with experimental details and modification described previosly32. At least five replicates of five flies were tested per genotype.…”

Geomagnetic field absence reduces adult body weight of a migratory insect by disrupting feeding behavior and appetite regulation

“…Interestingly, recent studies showed field intensity-dependent changes in the production of reactive oxygen species (ROS) which are regarded as signaling molecules for appetite-related neurons (Drougard et al, 2015;Sherrard et al, 2018;Van Huizen et al, 2019). Moreover, magnetic responses of adipokinetic hormone (AKH)/ AKH receptor (AKHR) signaling, reported to be involved in appetite regulation (Gáliková et al, 2017;Lin et al, 2019), was also found in adult rice planthoppers . Therefore, we speculated that the GMF absence-induced body weight decrease observed in rice planthoppers could be due to appetite loss and reduced feeding.…”