title: Looking at the metabolic consequences of the colchicine-based in vivo autophagic flux assay.
abstract: Monitoring autophagic flux in vivo or in organs remains limited and the ideal methods relative to the techniques possible with cell culture may not exist. Recently, a few papers have demonstrated the feasibility of measuring autophagic flux in vivo by intraperitoneal (IP) injection of pharmacological agents (chloroquine, leupeptin, vinblastine, and colchicine). However, the metabolic consequences of the administration of these drugs remain largely unknown. Here, we report that 0.8 mg/kg/day IP colchicine increased LC3-II protein levels in the liver of fasted trout, supporting the usefulness of this drug for studying autophagic flux in vivo in our model organism. This effect was accompanied by a decrease of plasma glucose concentration associated with a fall in the mRNA levels of gluconeogenesis-related genes. Concurrently, triglycerides and lipid droplets content in the liver increased. In contrast, transcript levels of β-oxidation-related gene Cpt1a dropped significantly. Together, these results match with the reported role of autophagy in the regulation of glucose homeostasis and intracellular lipid stores, and highlight the importance of considering these effects when using colchicine as an in vivo "autophagometer."
authors.affiliation: a INRA, UR1067 Nutrition Métabolisme Aquaculture , St-Pée-sur-Nivelle , France.
authors.forename: Iban
authors.initials: I
authors.lastname: Seiliez
authors.affiliation: a INRA, UR1067 Nutrition Métabolisme Aquaculture , St-Pée-sur-Nivelle , France.
authors.forename: Ikram
authors.initials: I
authors.lastname: Belghit
authors.affiliation: a INRA, UR1067 Nutrition Métabolisme Aquaculture , St-Pée-sur-Nivelle , France.
authors.forename: Yujie
authors.initials: Y
authors.lastname: Gao
authors.affiliation: a INRA, UR1067 Nutrition Métabolisme Aquaculture , St-Pée-sur-Nivelle , France.
authors.forename: Sandrine
authors.initials: S
authors.lastname: Skiba-Cassy
authors.affiliation: a INRA, UR1067 Nutrition Métabolisme Aquaculture , St-Pée-sur-Nivelle , France.
authors.forename: Karine
authors.initials: K
authors.lastname: Dias
authors.affiliation: a INRA, UR1067 Nutrition Métabolisme Aquaculture , St-Pée-sur-Nivelle , France.
authors.forename: Marianne
authors.initials: M
authors.lastname: Cluzeaud
authors.affiliation: b Clermont Université, Université d'Auvergne, Unité de Nutrition Humaine , Clermont-Ferrand , France.|c INRA, UMR1019 UNH, CRNH Auvergne , Clermont-Ferrand , France.
authors.forename: Didier
authors.initials: D
authors.lastname: Rémond
authors.affiliation: b Clermont Université, Université d'Auvergne, Unité de Nutrition Humaine , Clermont-Ferrand , France.|c INRA, UMR1019 UNH, CRNH Auvergne , Clermont-Ferrand , France.
authors.forename: Nordine
authors.initials: N
authors.lastname: Hafnaoui
authors.affiliation: d CNRS, IBGC, UMR5095 , Bordeaux , France.|e Universite de Bordeaux, IBGC, UMR5095 , Bordeaux , France.|f Universite de Bordeaux, Service Commun de Microscopie , Bordeaux , France.
authors.forename: Bénédicte
authors.initials: B
authors.lastname: Salin
authors.affiliation: d CNRS, IBGC, UMR5095 , Bordeaux , France.|e Universite de Bordeaux, IBGC, UMR5095 , Bordeaux , France.
authors.forename: Nadine
authors.initials: N
authors.lastname: Camougrand
authors.affiliation: a INRA, UR1067 Nutrition Métabolisme Aquaculture , St-Pée-sur-Nivelle , France.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Panserat
mesh_terms: D000263:Adenylate Kinase / Q000378:metabolism; D000597:Amino Acids, Branched-Chain / Q000378:metabolism; D000818:Animals; D001343:Autophagy / Q000187:drug effects* / Q000235:genetics; D015415:Biomarkers / Q000378:metabolism; D050260:Carbohydrate Metabolism / Q000187:drug effects; D003078:Colchicine / Q000494:pharmacology*; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects; D004734:Energy Metabolism / Q000187:drug effects; D005234:Fatty Liver / Q000378:metabolism / Q000473:pathology; D029941:Fish Proteins / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D050356:Lipid Metabolism / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D008247:Lysosomes / Q000378:metabolism / Q000648:ultrastructure; D017686:Oncorhynchus mykiss / Q000378:metabolism*; D010588:Phagosomes / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D013997:Time Factors; D014617:Vacuoles / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure
chemical_list: D000597:Amino Acids, Branched-Chain; D015415:Biomarkers; D029941:Fish Proteins; D058570:TOR Serine-Threonine Kinases; D000263:Adenylate Kinase; D003078:Colchicine
keywords: LC3-II; autophagic flux; colchicine; fish; hepatic metabolism; trout