Avian Orexin: Feed Intake Regulator or Something Else?

Abstract

Originally named for its expression in the posterior hypothalamus in rats and after the Greek word for "appetite", hypocretin, or orexin, as it is known today, gained notoriety as a neuropeptide regulating feeding behavior, energy homeostasis, and sleep. Orexin has been proven to be involved in both central and peripheral control of neuroendocrine functions, energy balance, and metabolism. Since its discovery, its ability to increase appetite as well as regulate feeding behavior has been widely explored in mammalian food production animals such as cattle, pigs, and sheep. It is also linked to neurological disorders, leading to its intensive investigation in humans regarding narcolepsy, depression, and Alzheimer's disease. However, in non-mammalian species, research is limited. In the case of avian species, orexin has been shown to have no central effect on feed-intake, however it was found to be involved in muscle energy metabolism and hepatic lipogenesis. This review provides current knowledge and summarizes orexin's physiological roles in livestock and pinpoints the present lacuna to facilitate further investigations.

Keywords: central regulation; metabolism; orexin; peripheral regulation; sleep-wake.

Figure 1

Impacts of orexin within mammalian and avian species. ? means the physiological function of orexin is still unknown or not well defined. In mammalian species of veterinary interest, such as mice, rats, sheep, cats, and dogs, orexin has been proven to be more than a neuropeptide. In addition to its central regulation of feeding behavior and sleep-wake cycles, orexin affects intestinal motility, pancreatic secretions, adipogenic factors, and energy homeostasis. In non-mammalian species such as chicken, research is limited, but shows a role of orexin in the central response to inflammatory and stress stimuli. Additionally, orexin in avian species has a peripheral influence on muscle mitochondrial dynamics and function, as well as hepatic stress response and lipogenic factors. Major gaps exist in our understanding of orexin’s influence on other peripheral tissue in avian species. Taken together, these findings demonstrate a necessity for further research into the diverse and undiscovered peripheral roles orexin plays in animal behavior, metabolism, and stress, particularly in avian species.

Figure 2

Orexin signaling pathways in mammalian (a) and avian species (b). “?” means that the downstream mediators are still not known or not well defined. Clear connections have been made to the link between orexin and the activation of energy sensing AMPK within the central nervous system of mammals. This provides a basis for connecting feeding behavior with orexin. Additionally, the ERK1/2 and Akt signaling pathways have been seen in hepatic response to orexin, inducing diverse cellular responses. While the main mechanism of action has yet to be determined, adipose tissue is shown to increase cytokines and other factors in response to orexin. In avian species, the ERK1/2 pathway has also been implicated in the liver response to orexin. Several mitochondrial related genes were shown to respond to orexin in avian muscle, but the direct mechanism of impact has yet to be elucidated. Culpable molecular signaling pathways have yet to be discovered in the avian central nervous system and adipose tissue response to orexin. AKT—Ak strain transforming kinase; AMPK—adenosine monophosphate-activated protein kinase; BAT—brown adipose tissue; CaMKKβ—Calcium/Calmodulin dependent protein kinase; cAMP—cyclic adenosine monophosphate; cORX-R1; chicken orexin receptor 1; cORX-R2—chicken orexin receptor 2; CREB—cAMP-response element binding protein; ERK1/2—extracellular-signal-regulated kinase 1/2; NFκB—nuclear factor kappa light chain enhancer of activated B cells; ORX-A—orexin-A; ORX-B—orexin-B; OXR1—orexin receptor 1; OXR2—orexin receptor 2; PKA—protein kinase A; PKC—protein kinase C; PLC—phospholipase C; P38—mitogen-associated protein kinase 38; WAT—white adipose tissue.