This review combined evidence on the central and peripheral regulation of feed intake (FI) in sheep, feed intake is a key determinant of body composition and the basic determinant of growth efficiency, metabolic health, and farm profitability. The findings indicate a strong route-dependent effect, where central intracerebroventricular (I.C.V.) injection of neuropeptides is potently effective: orexigenic signals (NPY, MCH, AGRP, orexin) stimulate FI, while an-orexigenic signals (leptin, α-MSH, rat-urocortin, QRFP43, angiotensin II, and enterostatin) suppress it. In stark contrast, intravenous or peripheral administration of these same agents typically produces weak or ineffective impacts; for example, leptin strongly suppresses FI when given I.C.V. but is ineffective intravenously, emphasizing the blood-brain barrier's pivotal role. This pattern also reveals notable species-specificity; as murine leptin fails to reduce FI in sheep unlike its ovine counterpart. Other centrally-acting modifiers include the cholecystokinin antagonist loxiglumide (increases FI), ACTH (decreases FI), and obestatin (complex modulatory effects), while peripherally-administered VIP shows no effect. Similarly, metabolic interventions show clear peripheral actions: glucose infusion decreases FI, while thiazolidinedione increases it and adiposity. Other peripheral modifiers, such as the acute-phase protein α-1-acid glycoprotein (AGP) and exogenous opioids like syndyphalin and morphine, demonstrate limited or context-dependent impacts on intake. This analysis delineates the complex integration of nutrient, neuroendocrine, and inflammatory signals governing ovine appetite, firmly establishing the central hypothalamus as the primary regulatory site and clarifying the limited direct efficacy of peripheral peptide administration. In conclusion, the regulatory landscape is defined by this critical barrier: peripheral injection of ghrelin, ACTH, glucose, or thiazolidinedione exerts significant effects on FI by engaging circumventricular organs, metabolic sensors, or non-neural tissues, whereas peripheral administration of leptin or loxiglumide remains without significant effect, as their primary anorexigenic and orexigenic actions, respectively, require direct central receptor engagement.
