Endocrine Abstracts

Background: A mutation in POMC in retriever dogs prevents production of the POMC-derived peptides β-MSH and β-endorphin but not α-MSH and is associated with weight, adiposity and owner-reported food motivation (Raffan et al, 2016). Melanocortin signalling is central to the control of energy homeostasis but the relative contribution of the POMC derived neuropeptides is not well understood because rodents produce only α-MSH whereas humans, like dogs, produce α-MSH and β-MSH.

Methods & Results: We recruited adult, healthy pet dogs and tested their eating behaviour and energy expenditure. An inaccessible food task showed dogs heterozygous for the mutation had greater incentive salience in response to a food stimulus (increased hunger). Voluntary food intake at a modified ad libitum meal was high (~2 kg) but there was no significant difference between genotypes. Vomiting/regurgitation occurred in 9/16 wild type dogs and 1/12 heterozygous dogs, which could imply different physiological responses to overfeeding. There was no measurable difference in the hedonic response to food. Resting energy expenditure measured using indirect calorimetry in the post-absorptive state was approximately 20% lower in dogs homozygous for the mutation than for wild type dogs (MR/hour=123 + βBM*Weight in Kg + βhomozygousPOMC*1 where βhomozygousPOMC = -42.3 (95% CI -62.9 to -21.7, P=0.0005) and βBM = 2.484 (-0.58 - 5.55, P=0.1).

Conclusion: Dogs bearing a POMC mutation which disrupts production of β-MSH and β-endorphin display increased hunger and markedly lower resting energy expenditure but normal satiety and hedonic responses. Although it remains possible β-endorphin deletion is in part responsible, these data implicate β-MSH as important in determining hunger and moderating energy expenditure, and that this role is independent of the presence of α-MSH.