title: Central metabolic sensing remotely controls nutrient-sensitive endocrine response inDrosophilavia Sir2/Sirt1-upd2-IIS axis.
abstract: Endocrine signaling is central in coupling organismal nutrient status with maintenance of systemic metabolic homeostasis. While local nutrient sensing within the insulinogenic tissue is well studied, distant mechanisms that relay organismal nutrient status in controlling metabolic-endocrine signaling are less well understood. Here, we report a novel mechanism underlying the distant regulation of the metabolic endocrine response inDrosophila melanogasterWe show that the communication between the fat body and insulin-producing cells (IPCs), important for the secretion ofDrosophilainsulin-like peptides (dILPs), is regulated by the master metabolic sensor Sir2/Sirt1. This communication involves a fat body-specific direct regulation of the JAK/STAT cytokine upd2 by Sir2/Sirt1. We have also uncovered the importance of this regulation in coupling nutrient inputs with dILP secretion, and distantly controlling insulin/IGF signaling (IIS) in the intestine. Our results provide fundamental mechanistic insights into the top-down control involving tissues that play key roles in metabolic sensing, endocrine signaling and nutrient uptake.
authors.affiliation: Department of Biological Sciences, Tata Institute of Fundamental Research, Homi Bhabha Road, Colaba, Mumbai 400 005, India.
authors.forename: Kushal K
authors.initials: KK
authors.lastname: Banerjee
authors.affiliation: Department of Biological Sciences, Tata Institute of Fundamental Research, Homi Bhabha Road, Colaba, Mumbai 400 005, India.
authors.forename: Rujuta S
authors.initials: RS
authors.lastname: Deshpande
authors.affiliation: Department of Biological Sciences, Tata Institute of Fundamental Research, Homi Bhabha Road, Colaba, Mumbai 400 005, India.
authors.forename: Pranavi
authors.initials: P
authors.lastname: Koppula
authors.affiliation: Department of Biological Sciences, Tata Institute of Fundamental Research, Homi Bhabha Road, Colaba, Mumbai 400 005, India.
authors.forename: Champakali
authors.initials: C
authors.lastname: Ayyub
authors.affiliation: Department of Biological Sciences, Tata Institute of Fundamental Research, Homi Bhabha Road, Colaba, Mumbai 400 005, India ullas@tifr.res.in.
authors.forename: Ullas
authors.identifier: 0000-0003-2612-1743
authors.initials: U
authors.lastname: Kolthur-Seetharam
mesh_terms: D000824:Animal Nutritional Physiological Phenomena; D000818:Animals; D029721:Drosophila Proteins / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000502:physiology*; D005216:Fat Body / Q000378:metabolism; D005260:Female; D006655:Histone Deacetylases / Q000378:metabolism*; D007328:Insulin / Q000378:metabolism*; D050417:Insulin-Secreting Cells / Q000378:metabolism; D061385:Insulins / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism; D015398:Signal Transduction; D056564:Sirtuin 1 / Q000378:metabolism*; D037761:Sirtuins / Q000378:metabolism*
chemical_list: D029721:Drosophila Proteins; C570846:Ilp5 protein, Drosophila; D007328:Insulin; D061385:Insulins; C508880:Upd2 protein, Drosophila; C447899:Sirt2 protein, Drosophila; D056564:Sirtuin 1; D037761:Sirtuins; D006655:Histone Deacetylases
keywords: DILP secretion; Insulin secretion; Insulin signaling; Intestine; JAK/STAT ligand; Metabolic homeostasis; Metabolism; NAD+ sensor; Nutrient sensing