ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Endocrine Abstracts (2019) 63 S13.3 | DOI: 10.1530/endoabs.63.S13.3

Genetics of appetite regulation: Can an old dog teach us new tricks?

Giles Yeo


It is clear that the cause of obesity is a result of eating more than you burn. What is more complex to answer is why some people eat more than others? Over the past 20 years, insights from human and mouse genetics have illuminated multiple pathways within the brain that play a key role in the control of food intake. We now know that the brain leptin-melanocortin pathway is central to mammalian food intake control, with genetic disruption resulting in extreme obesity. These, however, remain rare, with the major burden of disease carried by those of us with ‘common obesity’. In recent years, genome-wide association studies have revealed more than 100 different candidate genes linked to BMI, with most, including many components of the melanocortin pathway, acting in the CNS and influencing food intake. So while severe disruption of the melanocortin pathway results in severe obesity, subtle variations in these same genes influence where you might sit in the normal distribution of BMI. As we now enter this ‘post-genomics’ world, can this new information influence our treatment and management of obese patients?

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