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Increased food intake with oxyntomodulin analogues
Samantha L Price1, James S Minnion1, Stephen R Bloom1
1Department of Investigative Medicine, Imperial College, London W12 0NN, United Kingdom.
Oxyntomodulin analogues (OXM) show promise for obesity treatment. However, some analogues increased food intake in rats, suggesting a glucagon receptor mechanism may be involved in this effect.
Area of Science:
- Pharmacology
- Endocrinology
- Obesity Research
Background:
- Oxyntomodulin (OXM) analogues are being developed as novel anti-obesity therapeutics.
- Initial screening revealed unexpected increases in food intake with certain OXM analogues in rat models.
Purpose of the Study:
- To investigate the mechanism behind increased food intake observed with OXM analogues.
- To determine the role of glucagon receptor activation in this phenomenon.
Main Methods:
- Administration of OXM analogues (OXM14, OXM15) and their Glu-3 variants to rats for 7 days.
- Measurement of food intake and body weight.
- In vitro assessment of GLP-1 and glucagon receptor efficacy at rat receptors.
Main Results:
- OXM14 and OXM15 (25 nmol/kg) significantly increased food intake by up to 20% in rats.
- No significant increase in body weight was observed.
- Glu-3 substituted analogues (OXM14E3, OXM15E3) did not increase food intake, suggesting a glucagon receptor-mediated effect.
Conclusions:
- The observed increase in food intake with certain OXM analogues is likely mediated by glucagon receptor activation.
- Modifying the analogue at position 3 (Glu-3 substitution) mitigates this effect.
- Further research is needed to optimize OXM analogues for obesity treatment by managing appetite regulation.
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