title: Gαq, Gγ1 and Plc21C control Drosophila body fat storage.
abstract: Adaptive mobilization of body fat is essential for energy homeostasis in animals. In insects, the adipokinetic hormone (Akh) systemically controls body fat mobilization. Biochemical evidence supports that Akh signals via a G protein-coupled receptor (GPCR) called Akh receptor (AkhR) using cyclic-AMP (cAMP) and Ca(2+) second messengers to induce storage lipid release from fat body cells. Recently, we provided genetic evidence that the intracellular calcium (iCa(2+)) level in fat storage cells controls adiposity in the fruit fly Drosophila melanogaster. However, little is known about the genes, which mediate Akh signalling downstream of the AkhR to regulate changes in iCa(2+). Here, we used thermogenetics to provide in vivo evidence that the GPCR signal transducers G protein α q subunit (Gαq), G protein γ1 (Gγ1) and Phospholipase C at 21C (Plc21C) control cellular and organismal fat storage in Drosophila. Transgenic modulation of Gαq, Gγ1 and Plc21C affected the iCa(2+) of fat body cells and the expression profile of the lipid metabolism effector genes midway and brummer, which results in severely obese or lean flies. Moreover, functional impairment of Gαq, Gγ1 and Plc21C antagonised Akh-induced fat depletion. This study characterizes Gαq, Gγ1 and Plc21C as anti-obesity genes and supports the model that Akh employs the Gαq/Gγ1/Plc21C module of iCa(2+) control to regulate lipid mobilization in adult Drosophila.
authors.affiliation: Abteilung Molekulare Entwicklungsbiologie, Forschungsgruppe Molekulare Physiologie, Max-Planck-Institut für biophysikalische Chemie, Göttingen 37077, Germany.
authors.forename: Jens
authors.initials: J
authors.lastname: Baumbach
authors.affiliation: Abteilung Molekulare Entwicklungsbiologie, Forschungsgruppe Molekulare Physiologie, Max-Planck-Institut für biophysikalische Chemie, Göttingen 37077, Germany.
authors.forename: Yanjun
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Abteilung Molekulare Entwicklungsbiologie, Forschungsgruppe Molekulare Physiologie, Max-Planck-Institut für biophysikalische Chemie, Göttingen 37077, Germany.
authors.forename: Philip
authors.initials: P
authors.lastname: Hehlert
authors.affiliation: Abteilung Molekulare Entwicklungsbiologie, Forschungsgruppe Molekulare Physiologie, Max-Planck-Institut für biophysikalische Chemie, Göttingen 37077, Germany. Electronic address: rkuehnl@gwdg.de.
authors.forename: Ronald P
authors.initials: RP
authors.lastname: Kühnlein
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D029721:Drosophila Proteins / Q000378:metabolism*; D004331:Drosophila melanogaster; D043802:GTP-Binding Protein alpha Subunits, Gq-G11 / Q000378:metabolism*; D044388:GTP-Binding Protein gamma Subunits / Q000378:metabolism*; D050356:Lipid Metabolism; D010740:Phospholipases / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D029721:Drosophila Proteins; D044388:GTP-Binding Protein gamma Subunits; C587156:Ggamma1 protein, Drosophila; D010740:Phospholipases; C000595361:Plc21C protein, Drosophila; D043802:GTP-Binding Protein alpha Subunits, Gq-G11; D002118:Calcium
keywords: Adipokinetic hormone; Calcium; Fat storage; Gαq; Gγ1; Plc21C