title: Constitutive activation of Drosophila CncC transcription factor reduces lipid formation in the fat body.
abstract: Accumulating evidence indicates that the vertebrate stress-response transcription factors Nrf1 and Nrf2 are involved in hepatic lipid metabolism. However, the underlying molecular mechanisms of Nrf1-and Nrf2-mediated lipid metabolism remain unclear. To elucidate the precise roles of Nrfs in this process, we analyzed the physiological role of CncC in lipid metabolism as a Drosophila model for vertebrate Nrf1 and Nrf2. We first examined whether CncC activity is repressed under physiological conditions through a species-conserved NHB1 (N-terminal homology box 1) domain, similar to that observed for Nrf1. Deletion of the NHB1 domain (CncCΔN) led to CncC-mediated rough-eye phenotypes and the induced expression of the CncC target gene gstD1 both in vivo and in vitro. Thus, we decided to explore how CncCΔN overexpression affects the formation of the fat body, which is the major lipid storage organ. Intriguingly, CncCΔN caused a significant reduction in lipid droplet size and triglyceride (TG) levels in the fat body compared to wild type. We found that CncCΔN induced a number of genes related to innate immunity that might have an effect on the regulation of cellular lipid storage. Our study provides new insights into the regulatory mechanism of CncC and its role in lipid homeostasis.
authors.affiliation: Laboratory for Genetic Code, Graduate School of Life and Medical Sciences, Doshisha University, Japan.
authors.forename: M Rezaul
authors.initials: MR
authors.lastname: Karim
authors.affiliation: Laboratory for Genetic Code, Graduate School of Life and Medical Sciences, Doshisha University, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Taniguchi
authors.affiliation: Laboratory for Genetic Code, Graduate School of Life and Medical Sciences, Doshisha University, Japan. Electronic address: akobayas@mail.doshisha.ac.jp.
authors.forename: Akira
authors.initials: A
authors.lastname: Kobayashi
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D004330:Drosophila / Q000378:metabolism*; D029721:Drosophila Proteins / Q000737:chemistry / Q000378:metabolism*; D005216:Fat Body / Q000378:metabolism*; D008055:Lipids / Q000096:biosynthesis*; D008297:Male; D008969:Molecular Sequence Data; D060888:Real-Time Polymerase Chain Reaction; D012097:Repressor Proteins / Q000737:chemistry / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid
chemical_list: D029721:Drosophila Proteins; D008055:Lipids; D012097:Repressor Proteins; C116463:cnc protein, Drosophila
keywords: Drosophila model; Fat body; Gene regulation; Innate immunity; Lipid homeostasis