title: Repeated ICV administration of oxyntomodulin causes a greater reduction in body weight gain than in pair-fed rats.
abstract: Oxyntomodulin (OXM) is a product of proglucagon processing in the intestine and the central nervous system. We reported that intracerebroventricular (ICV) and intranuclear administration of OXM caused an inhibition of food intake in rats (Dakin CL, Gunn I, Small CJ, Edwards CM, Hay DL, Smith DM, Ghatei MA, and Bloom SR. Endocrinology 142: 4244-4250, 2001). In this study, we investigated the effect of twice-daily ICV administration of OXM, 1 nmol, for 7 days. A pair-fed control was included. These animals were restricted to the food intake of the OXM group but injected twice daily with saline. OXM-treated animals gained significantly less weight than either control group (day 8: OXM, 12.2 +/- 1.9 g vs. pair fed, 21.0 +/- 2.1 g; P < 0.005). OXM treatment caused a reduction in epididymal white adipose tissue (OXM, 1.13 +/- 0.03 g vs. pair fed, 1.29 +/- 0.04 g; P < 0.05) and interscapular brown adipose tissue (OXM, 0.15 +/- 0.01 g vs. pair fed, 0.18 +/- 0.01 g; P < 0.05) and increased core temperature compared with saline control, suggestive of enhanced energy expenditure. The food restriction-induced suppression in plasma TSH, seen in the pair-fed group, was prevented by OXM, potentially via increased release of hypothalamic TRH. In summary, ICV OXM causes reduced body weight gain and body adiposity following chronic administration.
authors.affiliation: Endocrine Unit, Imperial College Faculty of Medicine, Hammersmith Hospital, London W12 0NN, United Kingdom.
authors.forename: Catherine L
authors.initials: CL
authors.lastname: Dakin
authors.forename: Caroline J
authors.initials: CJ
authors.lastname: Small
authors.forename: Adrian J
authors.initials: AJ
authors.lastname: Park
authors.forename: Asha
authors.initials: A
authors.lastname: Seth
authors.forename: Mohammad A
authors.initials: MA
authors.lastname: Ghatei
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Bloom
mesh_terms: D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism; D002001:Adipose Tissue, Brown / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D001831:Body Temperature / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D004334:Drug Administration Schedule; D004435:Eating / Q000187:drug effects / Q000502:physiology; D004763:Glucagon-Like Peptides / Q000008:administration & dosage*; D007031:Hypothalamus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D007276:Injections, Intraventricular; D008297:Male; D016555:Matched-Pair Analysis; D053772:Oxyntomodulin; D051381:Rats; D017208:Rats, Wistar; D013972:Thyrotropin / Q000096:biosynthesis / Q000097:blood; D015430:Weight Gain / Q000187:drug effects*
chemical_list: D053772:Oxyntomodulin; D004763:Glucagon-Like Peptides; D013972:Thyrotropin