745C Poster - 12. Physiology, metabolism and aging
Saturday April 09, 1:30 PM - 3:30 PM

Authors:
Nadja Ahrentløv; Stanislav Nagy; Olga Kubrak; Alina Malita; Takashi Koyama; Michael Texada; Kim Rewitz

Affiliation: Section for Cell and Neurobiology, Department of Biology, Copenhagen University, Denmark

Keywords:
b. metabolism; e. endocrine function

Maintaining metabolic homeostasis requires interorgan coordination and thus communication, mediated by endocrine signals. Organs with specialized functions sense changes in internal and external nutrient availability and release hormonal factors that coordinate energy intake, storage, and expenditure. In both flies and mammals, the gut, the largest endocrine organ and the first that encounters food after ingestion, is a source of many secreted signals that regulate metabolism. Human gut-derived hormones such as glucagon-like peptide 1 (GLP-1), which regulates both metabolism and appetite, are of great therapeutic value in the treatment of diabetes and obesity. GLP-1 promotes insulin secretion and underlies the “incretin effect,” in which ingested glucose induces a larger insulin release than glucose injected directly into the bloodstream, thus bypassing the gut. Insulin action is opposed by the peptide hormone glucagon, but gut hormones that regulate glucagon release are poorly defined.

Many proteins are predicted to be secreted, but the functions of most of these potential hormones are largely unknown; these factors thus represent a significant unexploited resource for the discovery of new endocrine signals from the intestine that affect metabolic balance. Like its mammalian analog, the small intestine, the Drosophila midgut contains enteroendocrine cells (EECs) that release a variety of known endocrine factors in response to nutritional quantity and quality. We have performed a large-scale EEC-specific in-vivo RNAi-based screen of secreted factors in adult flies with the goal of identifying gut-derived factors that regulate food intake and metabolism. Our phenotypic readouts included measures of male and female flies’ ability to survive during nutritional deprivation and their storage of energy (as lipids and glycogen). Among our hits we have found several gut-derived hormonal factors that play key roles in regulating metabolism and feeding behavior, some of which act in a sexually dimorphic manner by modulating the glucagon analog Adipokinetic hormone. Taken together our results identify several gut hormones that may be of relevance to the treatment of diabetes and obesity.