title: Towards the therapeutic use of intranasal neuropeptide administration in metabolic and cognitive disorders.
abstract: The nose provides an effective way for delivering neuropeptides to the central nervous system, bypassing the blood-brain barrier and avoiding systemic side effects. Thereby intranasal neuropeptide administration enables the modulation of central nervous signaling pathways of body weight regulation and cognitive functions. Central nervous control of energy homeostasis is assumed to rely on hypothalamic neuropeptidergic pathways that are triggered by the peripheral adiposity signals insulin and leptin conveying the amount of body fat to the brain. Melanocortins, including alpha-melanocyte stimulating hormone (alpha-MSH), are essential for inducing anorexigenic/catabolic effects, i.e. for inhibiting caloric intake and increasing energy expenditure. Insulin, in addition to its function as an adiposity signal, also influences memory formation. Here we present a series of studies on the intranasal administration of MSH/ACTH4-10, a melanocortin receptor agonist, and of insulin. Prolonged administration of MSH/ACTH4-10 induced weight loss in normal-weight, but not in overweight humans. Intranasal insulin reduced body fat and improved memory functions in the absence of adverse peripheral side effects. Our results may contribute to the future development of therapeutic strategies in disorders like obesity and cognitive impairments that derive from dysfunctions of central nervous neuropeptidergic pathways.
authors.affiliation: Department of Neuroendocrinology, University of Lübeck, Ratzeburger Allee 160, 23538 Lübeck, Germany. hallschmid@kfg.uni-luebeck.de
authors.forename: Manfred
authors.initials: M
authors.lastname: Hallschmid
authors.forename: Christian
authors.initials: C
authors.lastname: Benedict
authors.forename: Bernd
authors.initials: B
authors.lastname: Schultes
authors.forename: Boris
authors.initials: B
authors.lastname: Perras
authors.forename: Horst-Lorenz
authors.initials: HL
authors.lastname: Fehm
authors.forename: Werner
authors.initials: W
authors.lastname: Kern
authors.forename: Jan
authors.initials: J
authors.lastname: Born
mesh_terms: D000273:Adipose Tissue / Q000187:drug effects; D000281:Administration, Intranasal; D000324:Adrenocorticotropic Hormone / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D001835:Body Weight / Q000187:drug effects / Q000502:physiology*; D002490:Central Nervous System / Q000378:metabolism*; D003072:Cognition Disorders / Q000378:metabolism / Q000628:therapy*; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D007328:Insulin / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D009074:Melanocyte-Stimulating Hormones / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D008659:Metabolic Diseases / Q000378:metabolism / Q000628:therapy*; D009479:Neuropeptides / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D018697:Nootropic Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D009765:Obesity / Q000378:metabolism / Q000628:therapy; D010446:Peptide Fragments / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D044101:Receptors, Melanocortin / Q000819:agonists; D012528:Satiety Response / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D007004:Hypoglycemic Agents; D007328:Insulin; D009479:Neuropeptides; D018697:Nootropic Agents; D010446:Peptide Fragments; D044101:Receptors, Melanocortin; D000324:Adrenocorticotropic Hormone; D009074:Melanocyte-Stimulating Hormones; C011394:ACTH (4-10)