title: Sucralose Promotes Food Intake through NPY and a Neuronal Fasting Response.
abstract: Non-nutritive sweeteners like sucralose are consumed by billions of people. While animal and human studies have demonstrated a link between synthetic sweetener consumption and metabolic dysregulation, the mechanisms responsible remain unknown. Here we use a diet supplemented with sucralose to investigate the long-term effects of sweet/energy imbalance. In flies, chronic sweet/energy imbalance promoted hyperactivity, insomnia, glucose intolerance, enhanced sweet taste perception, and a sustained increase in food and calories consumed, effects that are reversed upon sucralose removal. Mechanistically, this response was mapped to the ancient insulin, catecholamine, and NPF/NPY systems and the energy sensor AMPK, which together comprise a novel neuronal starvation response pathway. Interestingly, chronic sweet/energy imbalance promoted increased food intake in mammals as well, and this also occurs through an NPY-dependent mechanism. Together, our data show that chronic consumption of a sweet/energy imbalanced diet triggers a conserved neuronal fasting response and increases the motivation to eat.
authors.affiliation: Charles Perkins Centre and School of Life and Environmental Sciences, The University of Sydney, Sydney, NSW 2006, Australia; Neuroscience Division, Garvan Institute of Medical Research, 384 Victoria Street, Darlinghurst, Sydney, NSW 2010, Australia.
authors.forename: Qiao-Ping
authors.initials: QP
authors.lastname: Wang
authors.affiliation: Charles Perkins Centre and School of Life and Environmental Sciences, The University of Sydney, Sydney, NSW 2006, Australia; Neuroscience Division, Garvan Institute of Medical Research, 384 Victoria Street, Darlinghurst, Sydney, NSW 2010, Australia.
authors.forename: Yong Qi
authors.initials: YQ
authors.lastname: Lin
authors.affiliation: Neuroscience Division, Garvan Institute of Medical Research, 384 Victoria Street, Darlinghurst, Sydney, NSW 2010, Australia.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Neuroscience Division, Garvan Institute of Medical Research, 384 Victoria Street, Darlinghurst, Sydney, NSW 2010, Australia.
authors.forename: Yana A
authors.initials: YA
authors.lastname: Wilson
authors.affiliation: Charles Perkins Centre and School of Life and Environmental Sciences, The University of Sydney, Sydney, NSW 2006, Australia; Neuroscience Division, Garvan Institute of Medical Research, 384 Victoria Street, Darlinghurst, Sydney, NSW 2010, Australia.
authors.forename: Lisa J
authors.initials: LJ
authors.lastname: Oyston
authors.affiliation: Charles Perkins Centre and School of Life and Environmental Sciences, The University of Sydney, Sydney, NSW 2006, Australia; Neuroscience Division, Garvan Institute of Medical Research, 384 Victoria Street, Darlinghurst, Sydney, NSW 2010, Australia.
authors.forename: James
authors.initials: J
authors.lastname: Cotterell
authors.affiliation: Neuroscience Division, Garvan Institute of Medical Research, 384 Victoria Street, Darlinghurst, Sydney, NSW 2010, Australia.
authors.forename: Yue
authors.initials: Y
authors.lastname: Qi
authors.affiliation: Charles Perkins Centre and School of Life and Environmental Sciences, The University of Sydney, Sydney, NSW 2006, Australia; Neuroscience Division, Garvan Institute of Medical Research, 384 Victoria Street, Darlinghurst, Sydney, NSW 2010, Australia.
authors.forename: Thang M
authors.initials: TM
authors.lastname: Khuong
authors.affiliation: Charles Perkins Centre and School of Life and Environmental Sciences, The University of Sydney, Sydney, NSW 2006, Australia; Neuroscience Division, Garvan Institute of Medical Research, 384 Victoria Street, Darlinghurst, Sydney, NSW 2010, Australia.
authors.forename: Noman
authors.initials: N
authors.lastname: Bakhshi
authors.affiliation: Charles Perkins Centre and School of Life and Environmental Sciences, The University of Sydney, Sydney, NSW 2006, Australia; Neuroscience Division, Garvan Institute of Medical Research, 384 Victoria Street, Darlinghurst, Sydney, NSW 2010, Australia.
authors.forename: Yoann
authors.initials: Y
authors.lastname: Planchenault
authors.affiliation: Neuroscience Division, Garvan Institute of Medical Research, 384 Victoria Street, Darlinghurst, Sydney, NSW 2010, Australia.
authors.forename: Duncan T
authors.initials: DT
authors.lastname: Browman
authors.affiliation: Charles Perkins Centre and School of Life and Environmental Sciences, The University of Sydney, Sydney, NSW 2006, Australia; Neuroscience Division, Garvan Institute of Medical Research, 384 Victoria Street, Darlinghurst, Sydney, NSW 2010, Australia.
authors.forename: Man Tat
authors.initials: MT
authors.lastname: Lau
authors.affiliation: Charles Perkins Centre and School of Life and Environmental Sciences, The University of Sydney, Sydney, NSW 2006, Australia; Neuroscience Division, Garvan Institute of Medical Research, 384 Victoria Street, Darlinghurst, Sydney, NSW 2010, Australia.
authors.forename: Tiffany A
authors.initials: TA
authors.lastname: Cole
authors.affiliation: Charles Perkins Centre and School of Life and Environmental Sciences, The University of Sydney, Sydney, NSW 2006, Australia.
authors.forename: Adam C N
authors.initials: AC
authors.lastname: Wong
authors.affiliation: Charles Perkins Centre and School of Life and Environmental Sciences, The University of Sydney, Sydney, NSW 2006, Australia.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Simpson
authors.affiliation: Sacred Heart College, Retreat Rd, Newtown, Geelong, Victoria 3220, Australia.
authors.forename: Adam R
authors.initials: AR
authors.lastname: Cole
authors.affiliation: IMBA, Institute of Molecular Biotechnology of the Austrian Academy of Sciences, Dr. Bohr Gasse 3-5, A-1030 Vienna Austria.
authors.forename: Josef M
authors.initials: JM
authors.lastname: Penninger
authors.affiliation: Neuroscience Division, Garvan Institute of Medical Research, 384 Victoria Street, Darlinghurst, Sydney, NSW 2010, Australia. Electronic address: h.herzog@garvan.org.au.
authors.forename: Herbert
authors.initials: H
authors.lastname: Herzog
authors.affiliation: Charles Perkins Centre and School of Life and Environmental Sciences, The University of Sydney, Sydney, NSW 2006, Australia; Neuroscience Division, Garvan Institute of Medical Research, 384 Victoria Street, Darlinghurst, Sydney, NSW 2010, Australia. Electronic address: greg.neely@sydney.edu.au.
authors.forename: G Gregory
authors.initials: GG
authors.lastname: Neely
mesh_terms: D000263:Adenylate Kinase / Q000378:metabolism; D000818:Animals; D001066:Appetite / Q000187:drug effects; D004298:Dopamine / Q000378:metabolism; D029721:Drosophila Proteins / Q000378:metabolism; D004331:Drosophila melanogaster / Q000187:drug effects / Q000502:physiology; D004435:Eating / Q000187:drug effects*; D002149:Energy Intake / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D005215:Fasting; D006706:Homeostasis / Q000187:drug effects; D006815:Hunger / Q000187:drug effects; D007328:Insulin / Q000378:metabolism; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D009478:Neuropeptide Y / Q000378:metabolism*; D009655:Octopamine / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism; D013395:Sucrose / Q000031:analogs & derivatives* / Q000494:pharmacology; D013549:Sweetening Agents / Q000494:pharmacology; D013649:Taste / Q000187:drug effects
chemical_list: D029721:Drosophila Proteins; D007328:Insulin; D009478:Neuropeptide Y; D011956:Receptors, Cell Surface; D013549:Sweetening Agents; C405956:gustatory receptor, Drosophila; D009655:Octopamine; D013395:Sucrose; C026285:trichlorosucrose; D000263:Adenylate Kinase; D004298:Dopamine