title: Insulin-like peptide 5 is a microbially regulated peptide that promotes hepatic glucose production.
abstract: OBJECTIVE
  Insulin-like peptide 5 (INSL5) is a recently identified gut hormone that is produced predominantly by L-cells in the colon, but its function is unclear. We have previously shown that colonic expression of the gene for the L-cell hormone GLP-1 is high in mice that lack a microbiota and thus have energy-deprived colonocytes. Our aim was to investigate if energy deficiency also affected colonic Insl5 expression and to identify a potential role of INSL5.
  
  
  METHODS
  We analyzed colonic Insl5 expression in germ-free (GF), conventionally raised (CONV-R), conventionalized (CONV-D) and antibiotic-treated mice, and also assessed the effect of dietary changes on colonic Insl5 expression. In addition, we characterized the metabolic phenotype of Insl5-/- mice.
  
  
  RESULTS
  We showed that colonic Insl5 expression was higher in GF and antibiotic-treated mice than in CONV-R mice, whereas Insl5 expression in the brain was higher in CONV-R versus GF mice. We also observed that colonic Insl5 expression was suppressed by increasing the energy supply in GF mice by colonization or high-fat feeding. We did not observe any differences in food intake, gut transit or oral glucose tolerance between Insl5-/- and wild-type mice. However, we showed impaired intraperitoneal glucose tolerance in Insl5-/- mice. We also observed improved insulin tolerance and reduced hepatic glucose production in Insl5-/- mice.
  
  
  CONCLUSIONS
  We have shown that colonic Insl5 expression is regulated by the gut microbiota and energy availability. We propose that INSL5 is a hormone that could play a role in promoting hepatic glucose production during periods of energy deprivation.
authors.affiliation: The Wallenberg Laboratory, Department of Molecular and Clinical Medicine, University of Gothenburg, 41345 Gothenburg, Sweden.
authors.forename: Ying Shiuan
authors.initials: YS
authors.lastname: Lee
authors.affiliation: The Wallenberg Laboratory, Department of Molecular and Clinical Medicine, University of Gothenburg, 41345 Gothenburg, Sweden; Institut National de la Santé et de la Recherche Médicale, U855, Lyon 69372, France; Université de Lyon, Lyon 69008, France; Université Lyon 1, Villeurbanne 69622, France.
authors.forename: Filipe
authors.initials: F
authors.lastname: De Vadder
authors.affiliation: The Wallenberg Laboratory, Department of Molecular and Clinical Medicine, University of Gothenburg, 41345 Gothenburg, Sweden.
authors.forename: Valentina
authors.initials: V
authors.lastname: Tremaroli
authors.affiliation: The Wallenberg Laboratory, Department of Molecular and Clinical Medicine, University of Gothenburg, 41345 Gothenburg, Sweden.
authors.forename: Anita
authors.initials: A
authors.lastname: Wichmann
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, U855, Lyon 69372, France; Université de Lyon, Lyon 69008, France; Université Lyon 1, Villeurbanne 69622, France.
authors.forename: Gilles
authors.initials: G
authors.lastname: Mithieux
authors.affiliation: The Wallenberg Laboratory, Department of Molecular and Clinical Medicine, University of Gothenburg, 41345 Gothenburg, Sweden; Novo Nordisk Foundation Center for Basic Metabolic Research, Section for Metabolic Receptology and Enteroendocrinology, Faculty of Health Sciences, University of Copenhagen, 2200 Copenhagen, Denmark. Electronic address: Fredrik.Backhed@wlab.gu.se.
authors.forename: Fredrik
authors.initials: F
authors.lastname: Bäckhed
keywords: Colon; Gut microbiota; Insulin-like peptide 5 (INSL5); Liver