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Am J Physiol Endocrinol Metab 283: E1173-E1177, 2002. First published July 30, 2002; doi:10.1152/ajpendo.00233.2002
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Vol. 283, Issue 6, E1173-E1177, December 2002

Repeated ICV administration of oxyntomodulin causes a greater reduction in body weight gain than in pair-fed rats

Catherine L. Dakin, Caroline J. Small, Adrian J. Park, Asha Seth, Mohammad A. Ghatei, and Stephen R. Bloom

Endocrine Unit, Imperial College Faculty of Medicine, Hammersmith Hospital, London W12 0NN, United Kingdom

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.

glucagon-like peptide-1; energy expenditure; core temperature


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