title: Fat body dSir2 regulates muscle mitochondrial physiology and energy homeostasis nonautonomously and mimics the autonomous functions of dSir2 in muscles.
abstract: Sir2 is an evolutionarily conserved NAD(+)-dependent deacetylase which has been shown to play a critical role in glucose and fat metabolism. In this study, we have perturbed Drosophila Sir2 (dSir2) expression, bidirectionally, in muscles and the fat body. We report that dSir2 plays a critical role in insulin signaling, glucose homeostasis, and mitochondrial functions. Importantly, we establish the nonautonomous functions of fat body dSir2 in regulating mitochondrial physiology and insulin signaling in muscles. We have identified a novel interplay between dSir2 and dFOXO at an organismal level, which involves Drosophila insulin-like peptide (dILP)-dependent insulin signaling. By genetic perturbations and metabolic rescue, we provide evidence to illustrate that fat body dSir2 mediates its effects on the muscles via free fatty acids (FFA) and dILPs (from the insulin-producing cells [IPCs]). In summary, we show that fat body dSir2 is a master regulator of organismal energy homeostasis and is required for maintaining the metabolic regulatory network across tissues.
authors.affiliation: Department of Biological Sciences, Tata Institute of Fundamental Research, Mumbai, India.
authors.forename: Kushal K
authors.initials: KK
authors.lastname: Banerjee
authors.forename: Champakali
authors.initials: C
authors.lastname: Ayyub
authors.forename: Samudra
authors.initials: S
authors.lastname: Sengupta
authors.forename: Ullas
authors.initials: U
authors.lastname: Kolthur-Seetharam
mesh_terms: D000818:Animals; D002331:Carnitine / Q000008:administration & dosage; D004330:Drosophila / Q000235:genetics* / Q000502:physiology; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004852:Epoxy Compounds / Q000008:administration & dosage; D005216:Fat Body / Q000502:physiology*; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D005260:Female; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D055785:Gene Knockdown Techniques; D053263:Gene Regulatory Networks; D005951:Glucose Tolerance Test; D006655:Histone Deacetylases / Q000235:genetics / Q000378:metabolism*; D006706:Homeostasis; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics / Q000378:metabolism; D007328:Insulin / Q000378:metabolism; D050356:Lipid Metabolism; D053078:Membrane Potential, Mitochondrial; D008928:Mitochondria / Q000502:physiology*; D009132:Muscles / Q000502:physiology*; D060888:Real-Time Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D015398:Signal Transduction; D037761:Sirtuins / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: C111892:DIAP2 protein, Drosophila; D029721:Drosophila Proteins; D004852:Epoxy Compounds; C477334:FOXO protein, Drosophila; D005230:Fatty Acids, Nonesterified; D051858:Forkhead Transcription Factors; C557617:GAL4 protein, Drosophila; D051034:Inhibitor of Apoptosis Proteins; D007328:Insulin; D014157:Transcription Factors; C447899:Sirt2 protein, Drosophila; D037761:Sirtuins; D006655:Histone Deacetylases; C054207:etomoxir; D002331:Carnitine