title: Metabolic Impact of Light Phase-Restricted Fructose Consumption Is Linked to Changes in Hypothalamic AMPK Phosphorylation and Melatonin Production in Rats.
abstract: Recent studies show that the metabolic effects of fructose may vary depending on the phase of its consumption along with the light/dark cycle. Here, we investigated the metabolic outcomes of fructose consumption by rats during either the light (LPF) or the dark (DPF) phases of the light/dark cycle. This experimental approach was combined with other interventions, including restriction of chow availability to the dark phase, melatonin administration or intracerebroventricular inhibition of adenosine monophosphate-activated protein kinase (AMPK) with Compound C. LPF, but not DPF rats, exhibited increased hypothalamic AMPK phosphorylation, glucose intolerance, reduced urinary 6-sulfatoxymelatonin (6-S-Mel) (a metabolite of melatonin) and increased corticosterone levels. LPF, but not DPF rats, also exhibited increased chow ingestion during the light phase. The mentioned changes were blunted by Compound C. LPF rats subjected to dark phase-restricted feeding still exhibited increased hypothalamic AMPK phosphorylation but failed to develop the endocrine and metabolic changes. Moreover, melatonin administration to LPF rats reduced corticosterone and prevented glucose intolerance. Altogether, the present data suggests that consumption of fructose during the light phase results in out-of-phase feeding due to increased hypothalamic AMPK phosphorylation. This shift in spontaneous chow ingestion is responsible for the reduction of 6-S-Mel and glucose intolerance.
authors.affiliation: Department of Pharmacology, Faculty of Medical Sciences, State University of Campinas, #105 Alexander Fleming St., Campinas SP 13092-140, Brazil. ju.almeidafaria@gmail.com.
authors.forename: Juliana de Almeida
authors.initials: JA
authors.lastname: Faria
authors.affiliation: Laboratory of Cell Signaling, Faculty of Medical Sciences, State University of Campinas, Carl von Linnaeus St., Campinas SP 13083-864, Brazil. thiagomatosaraujo@gmail.com.
authors.forename: Thiago Matos F
authors.initials: TM
authors.lastname: de Araújo
authors.affiliation: Laboratory of Cell Signaling, Faculty of Medical Sciences, State University of Campinas, Carl von Linnaeus St., Campinas SP 13083-864, Brazil. danirazolli@yahoo.com.br.
authors.forename: Daniela S
authors.initials: DS
authors.lastname: Razolli
authors.affiliation: Faculty of Applied Sciences, State University of Campinas, #1300 Pedro Zaccaria St., Limeira SP 13484-350, Brazil. leticia.isouza@gmail.com.
authors.forename: Letícia Martins
authors.initials: LM
authors.lastname: Ignácio-Souza
authors.affiliation: Department of Pharmacology, Faculty of Medical Sciences, State University of Campinas, #105 Alexander Fleming St., Campinas SP 13092-140, Brazil. dailson.ns@gmail.com.
authors.forename: Dailson Nogueira
authors.initials: DN
authors.lastname: Souza
authors.affiliation: Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo SP 05508-900, Brazil. silvana.bordin@gmail.com.
authors.forename: Silvana
authors.initials: S
authors.lastname: Bordin
authors.affiliation: Department of Pharmacology, Faculty of Medical Sciences, State University of Campinas, #105 Alexander Fleming St., Campinas SP 13092-140, Brazil. anhegf@fcm.unicamp.br.
authors.forename: Gabriel Forato
authors.initials: GF
authors.lastname: Anhê
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002940:Circadian Rhythm; D003345:Corticosterone / Q000097:blood; D004305:Dose-Response Relationship, Drug; D005632:Fructose / Q000009:adverse effects*; D018149:Glucose Intolerance; D007031:Hypothalamus / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008550:Melatonin / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000378:metabolism* / Q000652:urine; D010766:Phosphorylation; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: C054513:6-sulfatoxymelatonin; D005632:Fructose; D055372:AMP-Activated Protein Kinases; D008550:Melatonin; D003345:Corticosterone
keywords: AMPK; corticosterone; fructose; melatonin; out-of-phase feeding