title: Effects of Peripheral Neurotensin on Appetite Regulation and Its Role in Gastric Bypass Surgery.
abstract: Neurotensin (NT) is a peptide expressed in the brain and in the gastrointestinal tract. Brain NT inhibits food intake, but the effects of peripheral NT are less investigated. In this study, peripheral NT decreased food intake in both mice and rats, which was abolished by a NT antagonist. Using c-Fos immunohistochemistry, we found that peripheral NT activated brainstem and hypothalamic regions. The anorexigenic effect of NT was preserved in vagotomized mice but lasted shorter than in sham-operated mice. This in combination with a strong increase in c-Fos activation in area postrema after ip administration indicates that NT acts both through the blood circulation and the vagus. To improve the pharmacokinetics of NT, we developed a pegylated NT peptide, which presumably prolonged the half-life, and thus, the effect on feeding was extended compared with native NT. On a molecular level, the pegylated NT peptide increased proopiomelanocortin mRNA in the arcuate nucleus. We also investigated the importance of NT for the decreased food intake after gastric bypass surgery in a rat model of Roux-en-Y gastric bypass (RYGB). NT was increased in plasma and in the gastrointestinal tract in RYGB rats, and pharmacological antagonism of NT increased food intake transiently in RYGB rats. Taken together, our data suggest that NT is a metabolically active hormone, which contributes to the regulation of food intake.
authors: Laboratory for Molecular Pharmacology (C.R., L.J.S., Z.R., B.S., A.N.M., B.Ho.), Department of Neuroscience and Pharmacology, and Department of Biomedical Sciences (B.Ha., J.J.H.), Faculty of Health Sciences, University of Copenhagen, DK-2200 Copenhagen, Denmark; Section for Metabolic Receptology (C.R., L.J.S., Z.R., B.S., A.N.M., B.Ho.) and Section for Translational Metabolic Physiology (B.Ha., J.J.H.), the Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health Sciences, University of Copenhagen, DK-2200 Copenhagen, Denmark; Institute of Veterinary Physiology (T.B., C.L.F., T.A.L.), Vetsuisse Faculty, and Center for Integrative Human Physiology (T.A.L.), University of Zurich, CH-8057 Zurich, Switzerland; Institute of Biochemistry (K.B.-S., A.G.B.-S.), University of Leipzig, D-04103 Leipzig, Germany; Gubra ApS (L.S.D., J.J.), Hørsholm, DK-2970 Denmark; and Biomedicine Discovery Institute (Z.B.A.), Metabolic Disease and Obesity Program, Monash University, Melbourne, Victoria 3800, Australia.
authors: Cecilia
authors: C
authors: Ratner
authors: Laboratory for Molecular Pharmacology (C.R., L.J.S., Z.R., B.S., A.N.M., B.Ho.), Department of Neuroscience and Pharmacology, and Department of Biomedical Sciences (B.Ha., J.J.H.), Faculty of Health Sciences, University of Copenhagen, DK-2200 Copenhagen, Denmark; Section for Metabolic Receptology (C.R., L.J.S., Z.R., B.S., A.N.M., B.Ho.) and Section for Translational Metabolic Physiology (B.Ha., J.J.H.), the Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health Sciences, University of Copenhagen, DK-2200 Copenhagen, Denmark; Institute of Veterinary Physiology (T.B., C.L.F., T.A.L.), Vetsuisse Faculty, and Center for Integrative Human Physiology (T.A.L.), University of Zurich, CH-8057 Zurich, Switzerland; Institute of Biochemistry (K.B.-S., A.G.B.-S.), University of Leipzig, D-04103 Leipzig, Germany; Gubra ApS (L.S.D., J.J.), Hørsholm, DK-2970 Denmark; and Biomedicine Discovery Institute (Z.B.A.), Metabolic Disease and Obesity Program, Monash University, Melbourne, Victoria 3800, Australia.
authors: Louise J
authors: LJ
authors: Skov
authors: Laboratory for Molecular Pharmacology (C.R., L.J.S., Z.R., B.S., A.N.M., B.Ho.), Department of Neuroscience and Pharmacology, and Department of Biomedical Sciences (B.Ha., J.J.H.), Faculty of Health Sciences, University of Copenhagen, DK-2200 Copenhagen, Denmark; Section for Metabolic Receptology (C.R., L.J.S., Z.R., B.S., A.N.M., B.Ho.) and Section for Translational Metabolic Physiology (B.Ha., J.J.H.), the Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health Sciences, University of Copenhagen, DK-2200 Copenhagen, Denmark; Institute of Veterinary Physiology (T.B., C.L.F., T.A.L.), Vetsuisse Faculty, and Center for Integrative Human Physiology (T.A.L.), University of Zurich, CH-8057 Zurich, Switzerland; Institute of Biochemistry (K.B.-S., A.G.B.-S.), University of Leipzig, D-04103 Leipzig, Germany; Gubra ApS (L.S.D., J.J.), Hørsholm, DK-2970 Denmark; and Biomedicine Discovery Institute (Z.B.A.), Metabolic Disease and Obesity Program, Monash University, Melbourne, Victoria 3800, Australia.
authors: Zindy
authors: Z
authors: Raida
authors: Laboratory for Molecular Pharmacology (C.R., L.J.S., Z.R., B.S., A.N.M., B.Ho.), Department of Neuroscience and Pharmacology, and Department of Biomedical Sciences (B.Ha., J.J.H.), Faculty of Health Sciences, University of Copenhagen, DK-2200 Copenhagen, Denmark; Section for Metabolic Receptology (C.R., L.J.S., Z.R., B.S., A.N.M., B.Ho.) and Section for Translational Metabolic Physiology (B.Ha., J.J.H.), the Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health Sciences, University of Copenhagen, DK-2200 Copenhagen, Denmark; Institute of Veterinary Physiology (T.B., C.L.F., T.A.L.), Vetsuisse Faculty, and Center for Integrative Human Physiology (T.A.L.), University of Zurich, CH-8057 Zurich, Switzerland; Institute of Biochemistry (K.B.-S., A.G.B.-S.), University of Leipzig, D-04103 Leipzig, Germany; Gubra ApS (L.S.D., J.J.), Hørsholm, DK-2970 Denmark; and Biomedicine Discovery Institute (Z.B.A.), Metabolic Disease and Obesity Program, Monash University, Melbourne, Victoria 3800, Australia.
authors: Thomas
authors: T
authors: Bächler
authors: Laboratory for Molecular Pharmacology (C.R., L.J.S., Z.R., B.S., A.N.M., B.Ho.), Department of Neuroscience and Pharmacology, and Department of Biomedical Sciences (B.Ha., J.J.H.), Faculty of Health Sciences, University of Copenhagen, DK-2200 Copenhagen, Denmark; Section for Metabolic Receptology (C.R., L.J.S., Z.R., B.S., A.N.M., B.Ho.) and Section for Translational Metabolic Physiology (B.Ha., J.J.H.), the Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health Sciences, University of Copenhagen, DK-2200 Copenhagen, Denmark; Institute of Veterinary Physiology (T.B., C.L.F., T.A.L.), Vetsuisse Faculty, and Center for Integrative Human Physiology (T.A.L.), University of Zurich, CH-8057 Zurich, Switzerland; Institute of Biochemistry (K.B.-S., A.G.B.-S.), University of Leipzig, D-04103 Leipzig, Germany; Gubra ApS (L.S.D., J.J.), Hørsholm, DK-2970 Denmark; and Biomedicine Discovery Institute (Z.B.A.), Metabolic Disease and Obesity Program, Monash University, Melbourne, Victoria 3800, Australia.
authors: Kathrin
authors: K
authors: Bellmann-Sickert
authors: Laboratory for Molecular Pharmacology (C.R., L.J.S., Z.R., B.S., A.N.M., B.Ho.), Department of Neuroscience and Pharmacology, and Department of Biomedical Sciences (B.Ha., J.J.H.), Faculty of Health Sciences, University of Copenhagen, DK-2200 Copenhagen, Denmark; Section for Metabolic Receptology (C.R., L.J.S., Z.R., B.S., A.N.M., B.Ho.) and Section for Translational Metabolic Physiology (B.Ha., J.J.H.), the Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health Sciences, University of Copenhagen, DK-2200 Copenhagen, Denmark; Institute of Veterinary Physiology (T.B., C.L.F., T.A.L.), Vetsuisse Faculty, and Center for Integrative Human Physiology (T.A.L.), University of Zurich, CH-8057 Zurich, Switzerland; Institute of Biochemistry (K.B.-S., A.G.B.-S.), University of Leipzig, D-04103 Leipzig, Germany; Gubra ApS (L.S.D., J.J.), Hørsholm, DK-2970 Denmark; and Biomedicine Discovery Institute (Z.B.A.), Metabolic Disease and Obesity Program, Monash University, Melbourne, Victoria 3800, Australia.
authors: Christelle
authors: C
authors: Le Foll
authors: Laboratory for Molecular Pharmacology (C.R., L.J.S., Z.R., B.S., A.N.M., B.Ho.), Department of Neuroscience and Pharmacology, and Department of Biomedical Sciences (B.Ha., J.J.H.), Faculty of Health Sciences, University of Copenhagen, DK-2200 Copenhagen, Denmark; Section for Metabolic Receptology (C.R., L.J.S., Z.R., B.S., A.N.M., B.Ho.) and Section for Translational Metabolic Physiology (B.Ha., J.J.H.), the Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health Sciences, University of Copenhagen, DK-2200 Copenhagen, Denmark; Institute of Veterinary Physiology (T.B., C.L.F., T.A.L.), Vetsuisse Faculty, and Center for Integrative Human Physiology (T.A.L.), University of Zurich, CH-8057 Zurich, Switzerland; Institute of Biochemistry (K.B.-S., A.G.B.-S.), University of Leipzig, D-04103 Leipzig, Germany; Gubra ApS (L.S.D., J.J.), Hørsholm, DK-2970 Denmark; and Biomedicine Discovery Institute (Z.B.A.), Metabolic Disease and Obesity Program, Monash University, Melbourne, Victoria 3800, Australia.
authors: Bjørn
authors: B
authors: Sivertsen
authors: Laboratory for Molecular Pharmacology (C.R., L.J.S., Z.R., B.S., A.N.M., B.Ho.), Department of Neuroscience and Pharmacology, and Department of Biomedical Sciences (B.Ha., J.J.H.), Faculty of Health Sciences, University of Copenhagen, DK-2200 Copenhagen, Denmark; Section for Metabolic Receptology (C.R., L.J.S., Z.R., B.S., A.N.M., B.Ho.) and Section for Translational Metabolic Physiology (B.Ha., J.J.H.), the Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health Sciences, University of Copenhagen, DK-2200 Copenhagen, Denmark; Institute of Veterinary Physiology (T.B., C.L.F., T.A.L.), Vetsuisse Faculty, and Center for Integrative Human Physiology (T.A.L.), University of Zurich, CH-8057 Zurich, Switzerland; Institute of Biochemistry (K.B.-S., A.G.B.-S.), University of Leipzig, D-04103 Leipzig, Germany; Gubra ApS (L.S.D., J.J.), Hørsholm, DK-2970 Denmark; and Biomedicine Discovery Institute (Z.B.A.), Metabolic Disease and Obesity Program, Monash University, Melbourne, Victoria 3800, Australia.
authors: Louise S
authors: LS
authors: Dalbøge
authors: Laboratory for Molecular Pharmacology (C.R., L.J.S., Z.R., B.S., A.N.M., B.Ho.), Department of Neuroscience and Pharmacology, and Department of Biomedical Sciences (B.Ha., J.J.H.), Faculty of Health Sciences, University of Copenhagen, DK-2200 Copenhagen, Denmark; Section for Metabolic Receptology (C.R., L.J.S., Z.R., B.S., A.N.M., B.Ho.) and Section for Translational Metabolic Physiology (B.Ha., J.J.H.), the Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health Sciences, University of Copenhagen, DK-2200 Copenhagen, Denmark; Institute of Veterinary Physiology (T.B., C.L.F., T.A.L.), Vetsuisse Faculty, and Center for Integrative Human Physiology (T.A.L.), University of Zurich, CH-8057 Zurich, Switzerland; Institute of Biochemistry (K.B.-S., A.G.B.-S.), University of Leipzig, D-04103 Leipzig, Germany; Gubra ApS (L.S.D., J.J.), Hørsholm, DK-2970 Denmark; and Biomedicine Discovery Institute (Z.B.A.), Metabolic Disease and Obesity Program, Monash University, Melbourne, Victoria 3800, Australia.
authors: Bolette
authors: B
authors: Hartmann
authors: Laboratory for Molecular Pharmacology (C.R., L.J.S., Z.R., B.S., A.N.M., B.Ho.), Department of Neuroscience and Pharmacology, and Department of Biomedical Sciences (B.Ha., J.J.H.), Faculty of Health Sciences, University of Copenhagen, DK-2200 Copenhagen, Denmark; Section for Metabolic Receptology (C.R., L.J.S., Z.R., B.S., A.N.M., B.Ho.) and Section for Translational Metabolic Physiology (B.Ha., J.J.H.), the Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health Sciences, University of Copenhagen, DK-2200 Copenhagen, Denmark; Institute of Veterinary Physiology (T.B., C.L.F., T.A.L.), Vetsuisse Faculty, and Center for Integrative Human Physiology (T.A.L.), University of Zurich, CH-8057 Zurich, Switzerland; Institute of Biochemistry (K.B.-S., A.G.B.-S.), University of Leipzig, D-04103 Leipzig, Germany; Gubra ApS (L.S.D., J.J.), Hørsholm, DK-2970 Denmark; and Biomedicine Discovery Institute (Z.B.A.), Metabolic Disease and Obesity Program, Monash University, Melbourne, Victoria 3800, Australia.
authors: Annette G
authors: AG
authors: Beck-Sickinger
authors: Laboratory for Molecular Pharmacology (C.R., L.J.S., Z.R., B.S., A.N.M., B.Ho.), Department of Neuroscience and Pharmacology, and Department of Biomedical Sciences (B.Ha., J.J.H.), Faculty of Health Sciences, University of Copenhagen, DK-2200 Copenhagen, Denmark; Section for Metabolic Receptology (C.R., L.J.S., Z.R., B.S., A.N.M., B.Ho.) and Section for Translational Metabolic Physiology (B.Ha., J.J.H.), the Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health Sciences, University of Copenhagen, DK-2200 Copenhagen, Denmark; Institute of Veterinary Physiology (T.B., C.L.F., T.A.L.), Vetsuisse Faculty, and Center for Integrative Human Physiology (T.A.L.), University of Zurich, CH-8057 Zurich, Switzerland; Institute of Biochemistry (K.B.-S., A.G.B.-S.), University of Leipzig, D-04103 Leipzig, Germany; Gubra ApS (L.S.D., J.J.), Hørsholm, DK-2970 Denmark; and Biomedicine Discovery Institute (Z.B.A.), Metabolic Disease and Obesity Program, Monash University, Melbourne, Victoria 3800, Australia.
authors: Andreas N
authors: AN
authors: Madsen
authors: Laboratory for Molecular Pharmacology (C.R., L.J.S., Z.R., B.S., A.N.M., B.Ho.), Department of Neuroscience and Pharmacology, and Department of Biomedical Sciences (B.Ha., J.J.H.), Faculty of Health Sciences, University of Copenhagen, DK-2200 Copenhagen, Denmark; Section for Metabolic Receptology (C.R., L.J.S., Z.R., B.S., A.N.M., B.Ho.) and Section for Translational Metabolic Physiology (B.Ha., J.J.H.), the Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health Sciences, University of Copenhagen, DK-2200 Copenhagen, Denmark; Institute of Veterinary Physiology (T.B., C.L.F., T.A.L.), Vetsuisse Faculty, and Center for Integrative Human Physiology (T.A.L.), University of Zurich, CH-8057 Zurich, Switzerland; Institute of Biochemistry (K.B.-S., A.G.B.-S.), University of Leipzig, D-04103 Leipzig, Germany; Gubra ApS (L.S.D., J.J.), Hørsholm, DK-2970 Denmark; and Biomedicine Discovery Institute (Z.B.A.), Metabolic Disease and Obesity Program, Monash University, Melbourne, Victoria 3800, Australia.
authors: Jacob
authors: J
authors: Jelsing
authors: Laboratory for Molecular Pharmacology (C.R., L.J.S., Z.R., B.S., A.N.M., B.Ho.), Department of Neuroscience and Pharmacology, and Department of Biomedical Sciences (B.Ha., J.J.H.), Faculty of Health Sciences, University of Copenhagen, DK-2200 Copenhagen, Denmark; Section for Metabolic Receptology (C.R., L.J.S., Z.R., B.S., A.N.M., B.Ho.) and Section for Translational Metabolic Physiology (B.Ha., J.J.H.), the Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health Sciences, University of Copenhagen, DK-2200 Copenhagen, Denmark; Institute of Veterinary Physiology (T.B., C.L.F., T.A.L.), Vetsuisse Faculty, and Center for Integrative Human Physiology (T.A.L.), University of Zurich, CH-8057 Zurich, Switzerland; Institute of Biochemistry (K.B.-S., A.G.B.-S.), University of Leipzig, D-04103 Leipzig, Germany; Gubra ApS (L.S.D., J.J.), Hørsholm, DK-2970 Denmark; and Biomedicine Discovery Institute (Z.B.A.), Metabolic Disease and Obesity Program, Monash University, Melbourne, Victoria 3800, Australia.
authors: Jens J
authors: JJ
authors: Holst
authors: Laboratory for Molecular Pharmacology (C.R., L.J.S., Z.R., B.S., A.N.M., B.Ho.), Department of Neuroscience and Pharmacology, and Department of Biomedical Sciences (B.Ha., J.J.H.), Faculty of Health Sciences, University of Copenhagen, DK-2200 Copenhagen, Denmark; Section for Metabolic Receptology (C.R., L.J.S., Z.R., B.S., A.N.M., B.Ho.) and Section for Translational Metabolic Physiology (B.Ha., J.J.H.), the Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health Sciences, University of Copenhagen, DK-2200 Copenhagen, Denmark; Institute of Veterinary Physiology (T.B., C.L.F., T.A.L.), Vetsuisse Faculty, and Center for Integrative Human Physiology (T.A.L.), University of Zurich, CH-8057 Zurich, Switzerland; Institute of Biochemistry (K.B.-S., A.G.B.-S.), University of Leipzig, D-04103 Leipzig, Germany; Gubra ApS (L.S.D., J.J.), Hørsholm, DK-2970 Denmark; and Biomedicine Discovery Institute (Z.B.A.), Metabolic Disease and Obesity Program, Monash University, Melbourne, Victoria 3800, Australia.
authors: Thomas A
authors: TA
authors: Lutz
authors: Laboratory for Molecular Pharmacology (C.R., L.J.S., Z.R., B.S., A.N.M., B.Ho.), Department of Neuroscience and Pharmacology, and Department of Biomedical Sciences (B.Ha., J.J.H.), Faculty of Health Sciences, University of Copenhagen, DK-2200 Copenhagen, Denmark; Section for Metabolic Receptology (C.R., L.J.S., Z.R., B.S., A.N.M., B.Ho.) and Section for Translational Metabolic Physiology (B.Ha., J.J.H.), the Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health Sciences, University of Copenhagen, DK-2200 Copenhagen, Denmark; Institute of Veterinary Physiology (T.B., C.L.F., T.A.L.), Vetsuisse Faculty, and Center for Integrative Human Physiology (T.A.L.), University of Zurich, CH-8057 Zurich, Switzerland; Institute of Biochemistry (K.B.-S., A.G.B.-S.), University of Leipzig, D-04103 Leipzig, Germany; Gubra ApS (L.S.D., J.J.), Hørsholm, DK-2970 Denmark; and Biomedicine Discovery Institute (Z.B.A.), Metabolic Disease and Obesity Program, Monash University, Melbourne, Victoria 3800, Australia.
authors: Zane B
authors: ZB
authors: Andrews
authors: Laboratory for Molecular Pharmacology (C.R., L.J.S., Z.R., B.S., A.N.M., B.Ho.), Department of Neuroscience and Pharmacology, and Department of Biomedical Sciences (B.Ha., J.J.H.), Faculty of Health Sciences, University of Copenhagen, DK-2200 Copenhagen, Denmark; Section for Metabolic Receptology (C.R., L.J.S., Z.R., B.S., A.N.M., B.Ho.) and Section for Translational Metabolic Physiology (B.Ha., J.J.H.), the Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health Sciences, University of Copenhagen, DK-2200 Copenhagen, Denmark; Institute of Veterinary Physiology (T.B., C.L.F., T.A.L.), Vetsuisse Faculty, and Center for Integrative Human Physiology (T.A.L.), University of Zurich, CH-8057 Zurich, Switzerland; Institute of Biochemistry (K.B.-S., A.G.B.-S.), University of Leipzig, D-04103 Leipzig, Germany; Gubra ApS (L.S.D., J.J.), Hørsholm, DK-2970 Denmark; and Biomedicine Discovery Institute (Z.B.A.), Metabolic Disease and Obesity Program, Monash University, Melbourne, Victoria 3800, Australia.
authors: Birgitte
authors: B
authors: Holst
mesh_terms: D000818:Animals; D001069:Appetite Regulation / Q000187:drug effects*; D004435:Eating / Q000187:drug effects; D005260:Female; D015390:Gastric Bypass; D008297:Male; D008810:Mice, Inbred C57BL; D009496:Neurotensin / Q000008:administration & dosage* / Q000037:antagonists & inhibitors / Q000097:blood; D017207:Rats, Sprague-Dawley; D013395:Sucrose; D014628:Vagotomy
chemical_list: D009496:Neurotensin; D013395:Sucrose