Peripheral Oxyntomodulin Reduces Food Intake and Body Weight Gain in Rats

Mar 6, 2004Endocrinology

Oxyntomodulin from outside the brain lowers eating and weight gain in rats

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Abstract

Intraperitoneal administration of Oxyntomodulin (OXM) reduced food intake and adiposity in rats over seven days.

OXM inhibited food intake in a dose-dependent manner without affecting gastric emptying.
Peripheral OXM administration decreased fasting plasma ghrelin levels.
Increased neuronal activation was observed in the arcuate nucleus (ARC) following OXM treatment.
Direct injection of OXM into the ARC led to a significant and sustained reduction in refeeding behavior after fasting.
The anorectic effects of OXM were blocked by a specific antagonist, indicating a potential action site in the ARC.
Different pathways may exist for the actions of OXM and GLP-1, as GLP-1 effects were not influenced by ARC administration of the antagonist.

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Oxyntomodulin (OXM) is a circulating gut hormone released post prandially from cells of the gastrointestinal mucosa. Given intracerebroventricularly to rats, it inhibits food intake and promotes weight loss. Here we report that peripheral (ip) administration of OXM dose-dependently inhibited both fast-induced and dark-phase food intake without delaying gastric emptying. Peripheral OXM administration also inhibited fasting plasma ghrelin. In addition, there was a significant increase in c-fos immunoreactivity, a marker of neuronal activation, in the arcuate nucleus (ARC). OXM injected directly into the ARC caused a potent and sustained reduction in refeeding after a fast. The anorectic actions of ip OXM were blocked by prior intra-ARC administration of the glucagon-like peptide-1 (GLP-1) receptor antagonist, exendin(9-39), suggesting that the ARC, lacking a complete blood-brain barrier, could be a potential site of action for circulating OXM. The actions of ip GLP-1, however, were not blocked by prior intra-ARC administration of exendin(9-39), indicating the potential existence of different OXM and GLP-1 pathways. Seven-day ip administration of OXM caused a reduction in the rate of body weight gain and adiposity. Circulating OXM may have a role in the regulation of food intake and body weight.

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Peripheral Oxyntomodulin Reduces Food Intake and Body Weight Gain in Rats

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