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Hypothalamic peptides as drug targets for obesity
1Imperial College at Hammersmith Hospital, London, UK.
Current Opinion in Pharmacology
|January 5, 2002
Summary
The melanocortin system plays a key role in obesity, with mutations in the MC4 receptor linked to severe obesity. New research highlights central regulators of food intake, offering potential therapeutic targets.
Area of Science:
- Neuroendocrinology
- Metabolic disease research
Background:
- The melanocortin system is implicated in regulating body weight.
- Mutations in the melanocortin MC4 receptor are associated with morbid obesity in humans.
- Melanin-concentrating hormone (MCH) and its receptors are involved in obesity pathogenesis.
Purpose of the Study:
- To review the current understanding of the melanocortin system's role in obesity.
- To highlight newly identified central regulators of food intake.
Main Methods:
- Review of recent genetic and pharmacological studies.
- Identification of novel molecular targets.
Main Results:
- Mutations in the melanocortin MC4 receptor confirm its importance in human obesity.
- Intranasal administration of a melanocortin fragment reduced body fat in humans.
- Overexpression of melanin-concentrating hormone (MCH) in mice leads to obesity.
- A second MCH receptor has been identified.
- Ghrelin, endocannabinoids, and glucagon-like peptide 2 are emerging as key central regulators of appetite.
Conclusions:
- The melanocortin system is a critical target for obesity research.
- Emerging central regulators of food intake offer new avenues for therapeutic intervention in obesity.