Selected hormonal and neurotransmitter mechanisms regulating feed intake in sheep

Abstract

Appetite control is a major issue in normal growth and in suboptimal growth performance settings. A number of hormones, in particular leptin, activate or inhibit orexigenic or anorexigenic neurotransmitters within the arcuate nucleus of the hypothalamus, where feed intake regulation is integrated. Examples of appetite regulatory neurotransmitters are the stimulatory neurotransmitters neuropeptide Y (NPY), agouti-related protein (AgRP), orexin and melanin-concentrating hormone and the inhibitory neurotransmitter, melanocyte-stimulating hormone (MSH). Examination of messenger RNA (using in situ hybridization and realtime PCR) and proteins (using immunohistochemistry) for these neurotransmitters in ruminants has indicated that physiological regulation occurs in response to fasting for several of these critical genes and proteins, especially AgRP and NPY. Moreover, intracerebroventricular injection of each of the four stimulatory neurotransmitters can increase feed intake in sheep and may also regulate either growth hormone, luteinizing hormone, cortisol or other hormones. In contrast, both leptin and MSH are inhibitory to feed intake in ruminants. Interestingly, the natural melanocortin-4 receptor (MC4R) antagonist, AgRP, as well as NPY can prevent the inhibition of feed intake after injection of endotoxin (to model disease suppression of appetite). Thus, knowledge of the mechanisms regulating feed intake in the hypothalamus may lead to mechanisms to increase feed intake in normal growing animals and prevent the wasting effects of severe disease in animals. Keywords: appetite, neuropeptide Y, proopiomelanocortin, leptin, sheep ImplicationsAppetite control by the brain is a critical component of the normal growth and development process as well as of major importance for reproduction. From an understanding of how these mechanisms function, we can develop specific protocols to support appetite in circumstances where feed intake is compromised. For example, development of a melanocortin-4 receptor antagonist that can cross the blood-brain barrier provides the opportunity to increase feed intake in normal animals, as well as to prevent the reduction in feed intake and perhaps body mass wasting in disease conditions. Other areas to consider might be early lactation or in metabolic disease circumstances. Thus, the study of brain control of appetite could have a major impact on improved growth and minimizing losses due to disease or other external stresses. IntroductionAppetite control is a complex process whereby multiple stimulatory and inhibitory inputs are integrated in the hypothalamus to yield an increase or decrease in feed intake. Initial lesioning studies in rodents determined a critical role for the arcuate nucleus (ARC) and ventromedial nucleus (VMN) in the control of appetite. Similar studies of lesions to the paraventricular nucleus (PVN) caused hyperphagia, while lesions of the lateral hypothalamic area (LHA) produced anorexia. These studies have been expanded upon to provide a current concept whereby th...

Hypothalamic Integration of Nutrient Status and Reproduction in the Sheep

“…Nutrient molecules such as glucose, propionate and fatty acids combined with endocrine signals such as leptin, insulin and ghrelin communicate either directly to the central nervous system or indirectly via peripheral afferent nerves and ultimately integrate within the central nervous system (reviewed by Sartin et al. , ) to regulate appetite regions of the hypothalamus. Appetite control is largely focused on the ARC, VMN, lateral hypothalamic area (LHA) with reciprocal connections to the brain stem with the nucleus tractus solitarius (NTS).…”

“…products of POMC, cocaine‐ and amphetamine‐related transcript or CRH) (Sartin et al. , ). The majority of the neuronal systems secreting orexigenic and anorexigenic neuropeptides are produced in the ARC at the base of the mediobasal hypothalamus.…”

“…Other brain areas involved in control of food intake are located primarily downstream of the ARC: including, the PVN, which produces anorexigenic peptides thyrotropin‐releasing hormone (TRH), CRH and oxytocin, the lateral hypothalamus (LHA) and perifornical area (PFA), secreting the orexigenic substances orexin A (OXA) and MCH (reviewed by Sartin et al. , ). We will focus on factors that have been shown experimentally to be involved in ovine feeding and reproduction and discuss potential players in need of further study.…”

TRIENNIAL GROWTH SYMPOSIUM: Neural regulation of feed intake: Modification by hormones, fasting, and disease1,2

“…Both stimulatory and inhibitory signals originate from the ARC and influence other secondary appetite neurons within the LHA, dorsomedial hypothalamus (DMH), VMN, and PVN and subsequently other areas of the CNS, with those signals emerging from the LHA-DMH being stimulatory to feed intake and those from the VMN and PVN being inhibitory (Table 1; for a review of hypothalamic appetite neurotransmitters, see Sartin et al, 2010). Although this model of first-order and second-order neurons was developed in the rat and provides an organization for testing and understanding the control of appetite, recent studies suggest this may not be appropriate for all species, particularly sheep (Qi et al, 2010).…”

“…See Qi et al (2008), Allen et al (2009). and Sartin et al (2010) for additional details. Gastrointestinal (GI), hepatic neural signals as well as hormonal signals are integrated at the nucleus tractus solitarius (NTS).…”