Technical Abstract: It is well established that reproductive function is metabolically gated. Numerous peripheral metabolic signals contribute to regulation of feeding behavior and energy homeostasis. However, the mechanisms whereby energy stores and metabolic cues influence appetite, energy homeostasis and fertility are yet to be completely understood. Adipose tissue is no longer considered as only a depot to store excess energy. In addition to leptin, recent reports have identified numerous genes, such as several neurotrophic factors, interleukins and other cytokines and biologically active factors i.e., insulin-like growth factor- I and -II and neuropeptide Y (NPY) and Agouti protein produced by adipose tissue. These factors could integrate appetite, growth and reproduction. Moreover, several mutations in the melanocortin- 4-receptor (MC4R) gene are associated with increased growth and feed efficiency. Thus, the genotype of MC4R that is expressed may alter the response to changes in energy availability. Leptin is a primary metabolic signal and is part of the adipose tissue-hypothalamic regulatory loop in the control of appetite, energy homeostasis and secretion of luteinizing hormone (LH) and growth hormone (GH). Leptin¿s action on appetite regulation is mediated by inhibition of hypothalamic NPY and stimulation of proopiomelanocortin (POMC) and melanocyte-stimulating hormone (MSH). Central administration of MSH not only suppressed appetite but down-regulated lipogenic pathways in adipose tissue and up-regulated lipolitic and gluconeogenic pathways in the liver. Leptin effects on gonadotropin releasing hormone (GnRH) /LH secretion are mediated by NPY and kisspeptin. Thus, leptin is an important link between metabolic status, neuroendocrine axis and subsequent fertility in the gilt and sow.