title: dMyc expression in the fat body affects DILP2 release and increases the expression of the fat desaturase Desat1 resulting in organismal growth.
abstract: Drosophila dMyc (dMyc) is known for its role in cell-autonomous regulation of growth. Here we address its role in the fat body (FB), a metabolic tissue that functions as a sensor of circulating nutrients to control the release of Drosophila Insulin-like peptides (Dilps) from the brain influencing growth and development. Our results show that expression of dMyc in the FB affects development and animal size. Expression of dMyc, but not of CycD/cdk4 or Rheb, in the FB diminishes the ability to retain Drosophila Insulin-like peptide-2 (DILP2) in the brain during starvation, suggesting that expression of dMyc mimics the signal that remotely controls the release of Dilps into the hemolymph. dMyc also affects glucose metabolism and increases the transcription of Glucose-transporter-1 mRNA, and of Hexokinase and Pyruvate-Kinase mRNAs, key regulators of glycolysis. These animals are able to counteract the increased levels of circulating trehalose induced by a high sugar diet leading to the conclusion that dMyc activity in the FB promotes glucose disposal. dMyc expression induces cell autonomous accumulation of triglycerides, which correlates with increased levels of Fatty Acid Synthase and Acetyl CoA Carboxylase mRNAs, enzymes responsible for lipid synthesis. We also found the expression of Stearoyl-CoA desaturase, Desat1 mRNA significantly higher in FB overexpressing dMyc. Desat1 is an enzyme that is necessary for monosaturation and production of fatty acids, and its reduction affects dMyc's ability to induce fat storage and resistance to animal survival. In conclusion, here we present novel evidences for dMyc function in the Drosophila FB in controlling systemic growth. We discovered that dMyc expression triggers cell autonomous mechanisms that control glucose and lipid metabolism to favor the storage of nutrients (lipids and sugars). In addition, the regulation of Desat1 controls the synthesis of triglycerides in FB and this may affect the humoral signal that controls DILP2 release in the brain.
authors.affiliation: Department of Biology, City College of the City University of New York, New York, NY 10031, USA.
authors.forename: Federica
authors.initials: F
authors.lastname: Parisi
authors.forename: Sara
authors.initials: S
authors.lastname: Riccardo
authors.forename: Sheri
authors.initials: S
authors.lastname: Zola
authors.forename: Carlina
authors.initials: C
authors.lastname: Lora
authors.forename: Daniela
authors.initials: D
authors.lastname: Grifoni
authors.forename: Lewis M
authors.initials: LM
authors.lastname: Brown
authors.forename: Paola
authors.initials: P
authors.lastname: Bellosta
mesh_terms: D000818:Animals; D049628:Body Size; D001921:Brain / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D004330:Drosophila / Q000201:enzymology / Q000254:growth & development* / Q000378:metabolism; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D005216:Fat Body / Q000166:cytology / Q000201:enzymology / Q000378:metabolism*; D044943:Fatty Acid Desaturases / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005508:Food Deprivation; D018507:Gene Expression Regulation, Developmental; D015971:Gene Expression Regulation, Enzymologic; D005947:Glucose / Q000378:metabolism; D006458:Hemolymph / Q000378:metabolism; D007328:Insulin / Q000378:metabolism; D007814:Larva / Q000201:enzymology / Q000235:genetics / Q000254:growth & development / Q000378:metabolism; D050356:Lipid Metabolism; D009479:Neuropeptides; D034622:RNA Interference; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016019:Survival Analysis; D013997:Time Factors; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014199:Trehalose / Q000378:metabolism; D014280:Triglycerides / Q000378:metabolism; D014921:Wings, Animal / Q000254:growth & development / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; C544178:ILP2 protein, Drosophila; D007328:Insulin; C102284:Myc protein, Drosophila; D009479:Neuropeptides; D012333:RNA, Messenger; D014157:Transcription Factors; D014280:Triglycerides; D014199:Trehalose; D044943:Fatty Acid Desaturases; C408225:desat1 protein, Drosophila; D005947:Glucose