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Am J Physiol Endocrinol Metab (July 30, 2002). doi:10.1152/ajpendo.00233.2002
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Articles in PresS, published online ahead of print July 30, 2002
Am J Physiol Endocrinol Metab, 10.1152/ajpendo.00233.2002
Submitted on May 29, 2002
Accepted on July 29, 2002

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

Catherine L Dakin1, Caroline J Small1, Adrian J Park1, Asha Seth1, Mohammad A Ghatei1, and Stephen R Bloom1*

1 Endocrine Unit, Imperial College Faculty of Medicine, London, London, United Kingdom

* To whom correspondence should be addressed. E-mail: s.bloom{at}ic.ac.uk.

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. In this study, we investigated the effect of twice-daily ICV administration of OXM, 1 nmole, for seven 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±1.9g vs. pair fed, 21.0±2.1g; P<0.005). OXM treatment caused a reduction in epididymal white adipose tissue (OXM, 1.13±0.03g vs. pair fed, 1.29±0.04g; P<0.05) and interscapular brown adipose tissue (OXM, 0.15±0.01g vs. pair fed, 0.18±0.01g; P<0.05) and increased core temperature, compared to 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.




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