Limostatin

Abstract: Lipids are the primary storage molecules and an essential source of energy in insects during reproduction, prolonged periods of flight, starvation, and diapause. The coordination center for insect lipid metabolism is the fat body, which is analogous to the vertebrate adipose tissue and liver. The fat body is primarily composed of adipocytes, which accumulate triacylglycerols in intracellular lipid droplets. Genomics and proteomics, together with functional analyses, such as RNA interference and CRISPR/Cas9-targeted genome editing, identified various genes involved in lipid metabolism and elucidated their functions. However, the endocrine control of insect lipid metabolism, in particular the roles of peptide hormones in lipogenesis and lipolysis are relatively less-known topics. In the current review, the neuropeptides that directly or indirectly affect insect lipid metabolism are introduced. The primary lipolytic and lipogenic peptide hormones are adipokinetic hormone and the brain insulin-like peptides (ILP2, ILP3, ILP5). Other neuropeptides, such as insulin-growth factor ILP6, neuropeptide F, allatostatin-A, corazonin, leucokinin, tachykinins and limostatin, might stimulate lipolysis, while diapause hormone-pheromone biosynthesis activating neuropeptide, short neuropeptide F, CCHamide-2, and the cytokines Unpaired 1 and Unpaired 2 might induce lipogenesis. Most of these peptides interact with one another, but mostly with insulin signaling, and therefore affect lipid metabolism indirectly. Peptide hormones are also involved in lipid metabolism during reproduction, flight, diapause, starvation, infections and immunity; these are also highlighted. The review concludes with a discussion of the potential of lipid metabolism-related peptide hormones in pest management.

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.