title: dSir2 deficiency in the fatbody, but not muscles, affects systemic insulin signaling, fat mobilization and starvation survival in flies.
abstract: Sir2 is an evolutionarily conserved NAD+ dependent protein. Although, SIRT1 has been implicated to be a key regulator of fat and glucose metabolism in mammals, the role of Sir2 in regulating organismal physiology, in invertebrates, is unclear. Drosophila has been used to study evolutionarily conserved nutrient sensing mechanisms, however, the molecular and metabolic pathways downstream to Sir2 (dSir2) are poorly understood. Here, we have knocked down endogenous dSir2 in a tissue specific manner using gene-switch gal4 drivers. Knockdown of dSir2 in the adult fatbody leads to deregulated fat metabolism involving altered expression of key metabolic genes. Our results highlight the role of dSir2 in mobilizing fat reserves and demonstrate that its functions in the adult fatbody are crucial for starvation survival. Further, dSir2 knockdown in the fatbody affects dilp5 (insulin-like-peptide) expression, and mediates systemic effects of insulin signaling. This report delineates the functions of dSir2 in the fatbody and muscles with systemic consequences on fat metabolism and insulin signaling. In conclusion, these findings highlight the central role that fatbody dSir2 plays in linking metabolism to organismal physiology and its importance for survival.
authors.affiliation: Tata Institute of Fundamental Research Department of Biological Sciences, Tata Institute of Fundamental Research, Colaba, Mumbai, India.
authors.forename: Kushal Kr
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: D000222:Adaptation, Physiological; D000818:Animals; D029721:Drosophila Proteins / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D004331:Drosophila melanogaster / Q000201:enzymology* / Q000235:genetics; D004734:Energy Metabolism / Q000235:genetics; D005216:Fat Body / Q000201:enzymology*; D055785:Gene Knockdown Techniques; D006655:Histone Deacetylases / Q000172:deficiency* / Q000235:genetics; D007328:Insulin / Q000378:metabolism*; D061385:Insulins / Q000378:metabolism; D050356:Lipid Metabolism / Q000235:genetics; D009132:Muscles / Q000201:enzymology*; D034622:RNA Interference; D015398:Signal Transduction / Q000235:genetics; D037761:Sirtuins / Q000172:deficiency* / Q000235:genetics; D013217:Starvation / Q000235:genetics; D013997:Time Factors
chemical_list: D029721:Drosophila Proteins; C570846:Ilp5 protein, Drosophila; D007328:Insulin; D061385:Insulins; C447899:Sirt2 protein, Drosophila; D037761:Sirtuins; D006655:Histone Deacetylases