Functional assessment of peripheral mechanisms controlling energy homeostasis in the domestic chicken

Abstract

Heavily-selected livestock production traits rarely come without compromise; altered physiology arising from intensive selection often gives rise to concern of a welfare trade-off. A particularly clear example of welfare challenge caused by genetic selection in chickens is the ‘broiler-breeder paradox’, wherein breeding populations of broiler-type birds selected for fast growth are feed-restricted in order to reduce growth and maintain reproductive viability at sexual maturity. In order to better-inform management and breeding strategies for alleviating reproductive problems resulting from genetic selection for growth, it is essential to develop a better understanding of the physiological processes underpinning growth. Whereas the molecular mechanisms governing energy balance in mammals have been relatively welldescribed, analogous avian systems have not received as much research attention and remain somewhat poorly understood. The broad aim of this doctoral project was to contribute to understanding of avian energy balance, particularly in the context of selection for high growth. Using an advanced broiler-layer intercross chicken line (AIL), high- and low-growth haplotypes at the locus encoding the cholecystokinin A receptor (CCKAR), underlying the most significant QTL for growth in chickens, were characterised. Of over 300 variations detected, a select panel spaced across the CCKAR locus were tested for prediction of bodyweight in a diverse cohort of chicken populations. One intronic SNP was found to be significant (p<0.05) and proximal to transcription factor binding sites. The effect of this locus on gross bodyweight remained significant into the 20th AIL generation (~20% at 10wk, p<0.05). In this otherwise effectively genetically homogeneous population, several specific physiological traits were predicted by CCKAR haplotype alone, yielding some clues as to the significance of perturbed cholecystokinin (CCK) signalling in broiler strains. While birds with high-growth CCKAR haplotype (HG) did not appear to consume more, feed conversion efficiency (FCE) was improved, at least for males, compared to low-growth (LG) (p<0.05). Visceral organ anatomies were morphologically disparate, with HG individuals exhibiting ~1/3 less gallbladder mass (p<0.01), and ~10% shorter GI tract (p<0.01) and metatarsal bone (p<0.05). Further gaps in knowledge of the expression of peripheral satiety hormones in chicken are addressed in this thesis. Tissue distributions for expression of CCK, gastrin, pancreatic polypeptide (PPY) and peptide YY (PYY), were mapped and their respective dynamic responses to nutritive state examined. CCK was found to be most highly expressed in the brain, whereas PYY, PPY and gastrin were far more abundant in distinct regions of the periphery. Interestingly, peripheral CCK was not responsive to short-term (<10h) satiety in experimental populations where PYY and gastrin were. PYY expression was found to be greatest in the pancreas and consistently upregulated within hours after feeding (p<0.01), whereas gastrin expression was confined to the gastric antrum and paradoxically highest in fasting birds (p<0.01). PPY expression is strictly limited to the pancreas and appears dependent on longerterm energy state. These results highlight similarities and differences to mammalian systems; notably, the avian pancreas seems to fulfil an exceptional role as a site of signal integration, perhaps unsurprising considering its disproportionate size compared to mammals. Indeed, pancreatic PYY appears to act as a primary peripheral short-term satiety hormone in birds. This body of work contributes to the understanding of avian energy balance and growth. An invaluable foundation for future research is formed by the identification of the major locations of production, and basic nutrient-responsive trends, for several peripheral avian hormones. Information on the growth role of CCKAR is consolidated and expanded upon, demonstrating a clear genetic contribution to maintenance organ morphology and overall growth. Such knowledge can be used to reliably assess and advise on selection and management of chickens to stem welfare concerns without compromising production. Comparisons between avian and other vertebrate endocrine systems make for interesting insight into the adaptive role of energy homeostatic mechanisms in divergent evolution of mammals and non-mammalian vertebrates. In some aspects, birds might better represent the ancestral phenotype from which each vertebrate clade arose

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