Control of lipid metabolism by gut Tachykinin hormones. Wei Song¹, Jan Veenstra³, Norbert Perrimon^1,2. 1) Department of Genetics, Harvard Medical School, Boston, MA 02115, USA; 2) Howard Hughes Medical Institute; 3) Université de Bordeaux, INCIA UMR 5287 CNRS, 33405 Talence, France.

   The interaction between the digestive and central nervous system (CNS) - necessary to maintain energy homeostasis, coordinate feeding, digestion, and other metabolic activities - is mediated in part by a series of hormones produced by both enteroendocrine cells (EEs) of the gut and the CNS. In many instances, the same brain-gut hormones are expressed in both the CNS and EEs complicating their functional analyses. As a result, we know little about the function of hormones produced from the gut. Using cell type specific genetic manipulation in Drosophila, we demonstrate that Tachykinins (TKs), one of the most abundant brain-gut hormones produced by EEs, regulate gut lipid metabolism in enterocytes (ECs) through activation of a GPCR/PKA signaling pathway. Further, unlike the knockdown of TKs in the CNS, gut-derived TKs do not result in an abnormal olfactory responses or defects in locomotor activities, thus demonstrating that brain-gut hormones can have fundamentally different physiological functions. Our findings illustrate the importance of analyzing the roles of brain-gut hormones in a tissue-specific manner to fully appreciate their diverse roles in physiology.