%0 Journal Article
%T Leptin in Anorexia and Cachexia Syndrome
%A Diana R. Engineer
%A Jose M. Garcia
%J International Journal of Peptides
%D 2012
%I Hindawi Publishing Corporation
%R 10.1155/2012/287457
%X Leptin is a product of the obese (OB) gene secreted by adipocytes in proportion to fat mass. It decreases food intake and increases energy expenditure by affecting the balance between orexigenic and anorexigenic hypothalamic pathways. Low leptin levels are responsible for the compensatory increase in appetite and body weight and decreased energy expenditure (EE) following caloric deprivation. The anorexia-cachexia syndrome is a complication of many chronic conditions including cancer, chronic obstructive pulmonary disease, congestive heart failure, chronic kidney disease, and aging, where the decrease in body weight and food intake is not followed by a compensatory increase in appetite or decreased EE. Crosstalk between leptin and inflammatory signaling known to be activated in these conditions may be responsible for this paradox. This manuscript will review the evidence and potential mechanisms mediating changes in the leptin pathway in the setting of anorexia and cachexia associated with chronic diseases. 1. Introdiction Leptin was discovered in 1994 by Friedman and colleagues after cloning an obese (OB) gene responsible for obesity in ob/ob mice [1]. It is a 167 amino acid peptide produced by adipocytes and it is a member of the adipocytokine family. Leptin has been noted to play a major role in body mass regulation by acting in the central nervous system to both stimulate energy expenditure and decrease food intake [2¨C4]. Named after the Greek word leptos, meaning lean, leptin was the first adipocyte-secreted hormone discovered, proving the active role of adipocytes in metabolic signaling. Leptin crosses the blood-brain barrier in a process that is highly regulated [5¨C8] and its receptors are found both centrally, in the hypothalamus, and peripherally, in pancreatic islets, liver, kidney, lung, skeletal muscle, and bone marrow [9]. Besides its key role on body weight regulation, leptin affects various metabolic pathways, including growth hormone (GH) signaling [10], insulin sensitivity, and lipogenesis [11]. While leptin levels are directly related to adiposity, there are several other factors resulting in individual variability. Leptin secretion is regulated by insulin, glucocorticoids, and catecholamines [3, 12, 13]. Also, females have significantly higher levels of leptin than men, for any degree of fat mass [14]. Along with adiponectin, leptin assists in peripheral insulin sensitization independent of body weight [15¨C17]. In leptin-deficient (ob/ob) mice, leptin injections led to dose-dependent reductions in serum glucose levels compared to fed
%U http://www.hindawi.com/journals/ijpep/2012/287457/