title: A glucagon-like endocrine pathway in Drosophila modulates both lipid and carbohydrate homeostasis.
abstract: The regulation of energy homeostasis is fundamental to all organisms. The Drosophila fat body serves as a repository for both triglycerides and glycogen, combining the energy storage functions of mammalian adipose and hepatic tissues, respectively. Here we show that mutation of the Drosophila adipokinetic hormone receptor (AKHR), a functional analog of the mammalian glucagon receptor, leads to abnormal accumulation of both lipid and carbohydrate. As a consequence of their obese phenotypes, AKHR mutants are markedly starvation resistant. We show that AKHR is expressed in the fat body, and, intriguingly, in a subset of gustatory neurons that mediate sweet taste. Genetic rescue experiments establish that the metabolic phenotypes arise exclusively from the fat body AKHR expression. Behavioral experiments demonstrate that AKHR mutants are neither sedentary nor hyperphagic, suggesting the metabolic abnormalities derive from a genetic propensity to retain energy stores. Taken together, our results indicate that a single endocrine pathway contributes to both lipid and carbohydrate catabolism in the Drosophila fat body.
authors.affiliation: Department of Pediatrics and Pharmacology, University of Texas Southwestern Medical School, Dallas, Texas 75390, USA. kamal.bharucha@utsouthwestern.edu
authors.forename: K N
authors.initials: KN
authors.lastname: Bharucha
authors.forename: P
authors.initials: P
authors.lastname: Tarr
authors.forename: S L
authors.initials: SL
authors.lastname: Zipursky
mesh_terms: D000818:Animals; D050260:Carbohydrate Metabolism; D004330:Drosophila / Q000235:genetics / Q000378:metabolism*; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D005216:Fat Body / Q000378:metabolism; D006706:Homeostasis; D050356:Lipid Metabolism; D009043:Motor Activity; D016254:Mutagenesis, Insertional; D009475:Neurons, Afferent / Q000378:metabolism; D010641:Phenotype; D018027:Receptors, Glucagon / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D015398:Signal Transduction; D013217:Starvation / Q000378:metabolism; D013649:Taste
chemical_list: C533337:AKHR protein, Drosophila; D029721:Drosophila Proteins; D018027:Receptors, Glucagon