Apelin, Orexin A and Ghrelin Levels in Obesity and the Metabolic Syndrome

Obesity has become a world-wide epidemic and a major burden for health-care system in countries that have adopted a Western lifestyle. The metabolic syndrome (MetS) is a cluster of risk factors predisposing to complications of obesity, including hypertension, hypercholesterolemia and impaired glucose tolerance. Patients with MetS are at high risk for diabetes and cardiovascular diseases. Essential features of MetS are insulin resistance and low grade systemic inflammation. During the past decade, several peptides regulating food intake, insulin sensitivity, blood pressure and inflammation have been discovered from adipose tissue and the gut. The physiological significance of many of these compounds is unclear. This study was established to determine whether circulating levels of three adipose tissue and gut derived peptides are altered in obesity and MetS. Apelin is a peptide detected in cardiovascular system, adipose tissue, gut, pancreas and hypothalamus. Administration of apelin in pharmacological doses affects food intake and potently stimulates heart rate and contraction in animals. In humans, peripheral administration of apelin causes a nitric oxide mediated arterial vasodilatation. Its expression in adipose tissue is up-regulated by inflammation and insulin. In the current study, plasma apelin level was increased in morbid obesity, yet the correlation to body adiposity during diet-induced weight loss was weaker than for the abundant adipokines leptin and adiponectin. Minor changes in apelin levels in response to a pronounced diet-induced weight loss in patients with MetS were related to arterial pressure and inflammation. Orexin A (OXA) was discovered as a hypothalamic peptide regulating food intake, wakefulness and sleep. Subsequent studies revealed that orexin A and its receptors are expressed in various tissues outside the central nervous system (CNS) such as the gastrointestinal tract and pancreas, where it modulates gastrointestinal motility and secretion of bicarbonate and insulin. It has been detected also in blood, yet source and the physiological role of circulating OXA is unknown. In the present study, plasma OXA level was increased in morbid obesity and decreased in obese children with Prader-Willi syndrome. Ghrelin is an orexigenic peptide secreted by stomach in response to low energy status. Plasma ghrelin level raises prior to and decreases after a meal, suggesting strong involvement in the regulation of food intake. The physiological significance of ghrelin in energy metabolism is controversial, since ghrelin-deficient and ghrelin receptor-deficient mice have normal growth rate and appetite. Ghrelin secretion may be regulated by postprandial signals and insulin, yet the current data is contradictory. In the present study, postprandial suppression of plasma ghrelin was impaired in patients with MetS independently of insulin. In addition, ghrelin increased in response to weight loss, but the increase was not sustained during prolonged weight reduction. In conclusion, the present study demonstrated that circulating apelin, orexin A and ghrelin levels are altered in obesity. These results help to define the roles of these peptides in obesity and MetS. National Library of Medicine Classification: QU 68, WD 210, WK 185, WK 820 Medical Subject Headings: APLN protein, human [Substance Name]; Blood Glucose; Body Mass Index; Energy Metabolism; Ghrelin; Insulin; Intercellular Signaling Peptides and Proteins; Leptin; Metabolic Syndrome X; Neuropeptides; Obesity; Obesity, Morbid; orexins [Substance Name]; Peptide Hormones; Prader-Willi Syndrome; Weight Loss