Regulation of Agouti-Related Protein and Pro-Opiomelanocortin Gene Expression in the Avian Arcuate Nucleus

Abstract

The arcuate nucleus is generally conserved across vertebrate taxa in its neuroanatomy and neuropeptide expression. Gene expression of agouti-related protein (AGRP), neuropeptide Y (NPY), pro-opiomelanocortin (POMC), and cocaine- and amphetamine-regulated transcript (CART) has been established in the arcuate nucleus of several bird species and co-localization demonstrated for AGRP and NPY. The proteins encoded by these genes exert comparable effects on food intake in birds after central administration to those seen in other vertebrates, with AGRP and NPY being orexigenic and CART and α-melanocyte-stimulating hormone anorexigenic. We have focused on the measurement of arcuate nucleus AGRP and POMC expression in several avian models in relation to the regulation of energy balance, incubation, stress, and growth. AGRP mRNA and POMC mRNA are, respectively, up- and downregulated after energy deprivation and restriction. This suggests that coordinated changes in the activity of AGRP and POMC neurons help to drive the homeostatic response to replace depleted energy stores in birds as in other vertebrates. While AGRP and POMC expression are generally positively and negatively correlated with food intake, respectively, we review here situations in some avian models in which AGRP gene expression is dissociated from the level of food intake and may have an influence on growth independent of changes in appetite. This suggests the possibility that the central melanocortin system exerts more pleiotropic functions in birds. While the neuroanatomical arrangement of AGRP and POMC neurons and the sensitivity of their activity to nutritional state appear generally conserved with other vertebrates, detailed knowledge is lacking of the key nutritional feedback signals acting on the avian arcuate nucleus and there appear to be significant differences between birds and mammals. In particular, recently identified avian leptin genes show differences between bird species in their tissue expression patterns and appear less closely linked in their expression to nutritional state. It is presently uncertain how the regulation of the central melanocortin system in birds is brought about in the situation of the apparently reduced importance of leptin and ghrelin compared to mammals.

Peripherally injected ghrelin and leptin reduce food hoarding and mass gain in the coal tit ( Periparus ater )

“…Whereas, satiety stimulates expression of pro-opiomelanocortin (POMC) in a different population of Arc neurons. The catabolic effects of POMC are in part caused by stimulating release of a-melanocyte-stimulating hormone (a-MSH) from the anterior pituitary, and its subsequent binding to melanocortin-4 receptors (MC4Rs) [50]. AgRP has opposing effects to POMC, as it acts as a competitive antagonist with a-MSH on MC4Rs, thereby stimulating food intake [50,51].…”

Intermittent fasting in chickens : Physiological mechanisms and welfare implications for broiler breeders

“…Circulating levels of insulin are correlated with food intake in chickens but are also a poor candidate for the role as a main peripheral energy signal as fasting plasma concentrations do not differ between lines selected for fat and lean body types. Central insulin injection also does not reduce food intake in laying-type chickens and has variable effects on the expression of orexigenic peptides (Boswell and Dunn, 2017).…”

“…In mammals, the main regulators appear to be leptin, released from adipose tissue, and ghrelin, expressed in the stomach, which repress and stimulate eating respectively. Although birds do produce ghrelin in the proventriculus with circulating levels increasing in fasting and decreasing with feeding, both central and peripheral injection of the hormone appears to decrease feeding behavior (Boswell and Dunn, 2017). The leptin gene is poorly conserved between mammals and birds and shows minimal expression in bird adipose tissue.…”

“…The VMH is typically considered the primary hypothalamic satiety center and fasting has been shown to increase expression of the neuronal activation marker c-Fos in the VMH of chickens (Yi et al, 2017). Most studies of central appetite regulation have however focused on the ARC, historically known as the "infundibular nucleus" (Boswell and Dunn, 2017). The ARC is well established as a center for energy balance regulation in mammals, regulating behaviors such as wheel running activity, overall energy expenditure and food intake in rodents (Boswell and Dunn, 2017;Thomas and Xue, 2018).…”

Hope, exploration, and equilibrated action schemes

“…Less is known about the role of AgRP and NPY in foraging in wild birds. However, in birds in general these neuropeptides show strong evolutionary conservation with mammals in terms of their amino acid sequences, the neuroanatomical arrangement of the neurons synthesising them in the hypothalamus, and the sensitivity of their gene expression to nutritional state (Boswell & Dunn 2017). In red junglefowl, as in rodents, AgRP expression is more sensitive to chronic food restriction, whereas NPY is more responsive to acute food restriction (Lees et al 2017), suggesting that the same dichotomy may exist in birds as well.…”