7522623a8a825c24596ff3fa3e04e787 pmc_34768822.pdf d2337fe034c6880fbfce16f07d018f874c09e425 pmc_34768822.pdf 4dfdaac6dfbcdeb87c3f022c298e3fdf1db8bf7351c08652cff695ccb8a04b5d pmc_34768822.pdf Title: Viral Infection Drives the Regulation of Feeding Behavior Related Genes in Salmo salar Subject: The feeding behavior in fish is a complex activity that relies on the ability of the brain to integrate multiple signals to produce appropriate responses in terms of food intake, energy expenditure, and metabolic activity. Upon stress cues including viral infection or mediators such as the proinflammatory cytokines, prostaglandins, and cortisol, both Pomc and Npy/Agrp neurons from the hypothalamus are stimulated, thus triggering a response that controls both energy storage and expenditure. However, how appetite modulators or neuro-immune cues link pathogenesis and energy homeostasis in fish remains poorly understood. Here, we provide the first evidence of a molecular linkage between inflammation and food intake in Salmon salar. We show that in vivo viral challenge with infectious pancreatic necrosis virus (IPNV) impacts food consumption by activating anorexic genes such as mc4r, crf, and pomcb and 5-HT in the brain of S. salar. At the molecular level, viral infection induces an overall reduction in lipid content in the liver, favoring the production of AA and EPA associated with the increment of elovl2 gene. In addition, infection upregulates leptin signaling and inhibits insulin signaling. These changes are accompanied by a robust inflammatory response represented by the increment of Il-1b, Il-6, Tnfa, and Pge2 as well as an increased cortisol level in vivo. Thus, we propose a model in which hypothalamic neurons respond to inflammatory cytokines and stress-related molecules and interact with appetite induction/inhibition. These findings provide evidence of crosstalk between pathogenesis-driven inflammation and hypothalamic–pituitary–adrenocortical axes in stress-induced food intake behavior in fish. Keywords: feeding behavior; lipid metabolism; inflammation; infection Author: David Muñoz, Ricardo Fuentes, Beatriz Carnicero, Andrea Aguilar, Nataly Sanhueza, Sergio San-Martin, Cristian Agurto, Andrea Donoso, Leonardo E. Valdivia, Jesús M. Miguez, Lluis Tort and Sebastián Boltana Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Thu Oct 21 17:42:47 2021 CEST ModDate: Thu Oct 21 17:49:06 2021 CEST Custom Metadata: no Metadata Stream: no Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 17 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 5487780 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- FYYAHQ+VnURWPalladioL-Bold Type 1 Custom yes yes no 10 0 OPZDHV+VnURWPalladioL Type 1 Custom yes yes no 15 0 WRLBHK+URWPalladioL-Ital Type 1 Custom yes yes no 19 0 EOYEXT+URWPalladioL-Bold Type 1 Custom yes yes no 24 0 QECEZT+URWPalladioL-BoldItal Type 1 Custom yes yes no 28 0 EUUUNU+URWPalladioL-Roma Type 1 Custom yes yes no 32 0 IRWHZX+TimesNewRomanPSMT Type 1C WinAnsi yes yes no 40 0 CKUPDE+TimesNewRomanPS-BoldItalicMT Type 1C WinAnsi yes yes 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2023-03-31 12:06:08 CEST Size: 5487780 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 520 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Destination: section.1 Item: Title: Results Destination: section.2 Children: Item: Title: IPNv Viral Infection Increases the Levels of Cortisol Destination: subsection.2.1 Item: Title: Upregulation of elovl2 in the Liver of Juvenile Salmon Is Linked with the Increases of AA and EPA during Infection with IPNv Destination: subsection.2.2 Item: Title: Anorexigenic Genes Are Upregulated during Infection in Juvenile Salmon Destination: subsection.2.3 Item: Title: Discussion Destination: section.3 Children: Item: Title: Pro-Inflammatory Cytokines Regulate Feeding Behavior Destination: subsection.3.1 Item: Title: The Gene elovl2 Is Upregulated during Inflammation to Promote the Accumulation of EPA in the Liver of Challenged Salmon Destination: subsection.3.2 Item: Title: A Set of the Anorexic Genes Are Upregulated by Leptin Signaling during Inflammation Destination: subsection.3.3 Item: Title: Materials and Methods Destination: section.4 Children: Item: Title: Animal and Hatchery Conditions Destination: subsection.4.1 Item: Title: Infectious Pancreatic Necrosis Virus (IPNv) Challenge Destination: subsection.4.2 Item: Title: RNA Extraction, cDNA Synthesis, and Transcript Quantification Destination: subsection.4.3 Item: Title: Monoamine Analysis Destination: subsection.4.4 Item: Title: Cortisol and Prostaglandin E2 ELISA Assays Destination: subsection.4.5 Item: Title: Lipid Content Destination: subsection.4.6 Item: Title: Statistical Analysis Destination: subsection.4.7 Item: Title: Conclusions Destination: section.5 Item: Title: References Destination: section.5 Info: Title: Viral Infection Drives the Regulation of Feeding Behavior Related Genes in Salmo salar Author: David Muñoz, Ricardo Fuentes, Beatriz Carnicero, Andrea Aguilar, Nataly Sanhueza, Sergio San-Martin, Cristian Agurto, Andrea Donoso, Leonardo E. Valdivia, Jesús M. Miguez, Lluis Tort and Sebastián Boltana Subject: The feeding behavior in fish is a complex activity that relies on the ability of the brain to integrate multiple signals to produce appropriate responses in terms of food intake, energy expenditure, and metabolic activity. Upon stress cues including viral infection or mediators such as the proinflammatory cytokines, prostaglandins, and cortisol, both Pomc and Npy/Agrp neurons from the hypothalamus are stimulated, thus triggering a response that controls both energy storage and expenditure. However, how appetite modulators or neuro-immune cues link pathogenesis and energy homeostasis in fish remains poorly understood. Here, we provide the first evidence of a molecular linkage between inflammation and food intake in Salmon salar. We show that in vivo viral challenge with infectious pancreatic necrosis virus (IPNV) impacts food consumption by activating anorexic genes such as mc4r, crf, and pomcb and 5-HT in the brain of S. salar. At the molecular level, viral infection induces an overall reduction in lipid content in the liver, favoring the production of AA and EPA associated with the increment of elovl2 gene. In addition, infection upregulates leptin signaling and inhibits insulin signaling. These changes are accompanied by a robust inflammatory response represented by the increment of Il-1b, Il-6, Tnfa, and Pge2 as well as an increased cortisol level in vivo. Thus, we propose a model in which hypothalamic neurons respond to inflammatory cytokines and stress-related molecules and interact with appetite induction/inhibition. These findings provide evidence of crosstalk between pathogenesis-driven inflammation and hypothalamic pituitary adrenocortical axes in stress-induced food intake behavior in fish. 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