© FD-Communications Inc. Obesity Surgery, 13, 2003 17 Obesity Surgery, 13, 17-22 Background: Ghrelin is a newly recognized gastric hormone with orexigenic and adipogenic properties, produced primarily by the stomach. Ghrelin is reduced in obesity. Weight loss is associated with an increase in fasting plasma ghrelin. We assessed the effect of massive weight loss on plasma ghrelin con- centrations and its correlation with serum leptin lev- els and the presence of type 2 diabetes mellitus (DM) in severely obese patients. Methods: A prospective study was conducted on 28 morbidly obese women (BMI 56.3±10.2 kg/m 2 ) who underwent gastric bypass, divided into 2 groups: 14 non-diabetics (NGT) and 14 type 2 diabetics (DM2). Ghrelin and leptin were evaluated before silastic ring transected vertical gastric bypass, and again 12 months postoperatively. Results: Fasting plasma ghrelin concentrations were 56% lower in NGT and 59% lower in DM2 com- pared with a lean control group (P<0.001). There was no difference in ghrelin levels between NGT and DM2 groups before and after surgery (P>0.05). Ghrelin was negatively correlated with leptin before gastric bypass surgery (r=0.51, P<0.01). The mean plasma ghrelin concentration decreased significantly after surgery in both groups (P<0.001). Conclusion: Ghrelin was inversely related to leptin concentrations. Presence of diabetes did not affect the ghrelin pattern. Reduced production of ghrelin after gastric bypass could be partly responsible for the lack of hyperphagia and thus for the weight loss. Key words: Ghrelin, leptin, weight loss, diabetes, morbid obesity, bariatric surgery, gastric bypass Introduction In the past two decades, there has been considerable evidence for a critical role that hypothalamic pep- tidergic systems play in the central regulation of appetite and metabolism. 1 The discovery of ghrelin 2 and its influence on appetite, fuel utilization, body weight, and body composition that is complementa- ry to ghrelin’s growth hormone (GH) -releasing effect 3 adds another component to the central regu- lation of energy balance. The name ghrelin contains “ghre” as the etymological root in many languages, for “growth”. Ghrelin was originally identified in rat stomach as the endogenous ligand for the GH secretagogue receptor (GHS-R). 4 In fact, it is evi- dent that ghrelin is a potent GH-releasing agent in both rodents 5,6 and humans, 7-10 especially in the fasting state. 11 In humans, ghrelin expression is found in the gastrointestinal tract, from the stomach to the colon, with the greatest concentration being in the fundus of the stomach. 12 The actions of ghrelin are not restricted to the hypothalamus; ghrelin has profound orexigenic properties with weight gain in animals 13 and enhancement in food intake in humans. 14 Other actions of ghrelin are stimulation of gastrin, result- ing in increase in acid secretion in the stomach. 15 Thus, the integrated action of ghrelin is to prepare the body for weight gain and energy accumulation, and ghrelin may ensure the provision of calories that GH requires for growth and repair. 16 Fasting stimulates ghrelin secretion by the stom- ach, and food intake suppresses ghrelin concentra- Ghrelin: a Gut-Brain Hormone: Effect of Gastric Bypass Surgery Bruno Geloneze, MD, PhD 1 ; Marcos A. Tambascia, MD, PhD 1 ; Victor F. Pilla, MD 2 ; Sylka R. Geloneze, MD 1 ; Enrico M. Repetto, MD 1 ; José C. Pareja MD, PhD 2 1 Endocrinology Service and 2 Obesity Surgery Unit, University of Campinas, UNICAMP, Brazil Reprint requests to: Bruno Geloneze, MD, PhD, University of Campinas, Rua Camargo Paes 251, 13073-350, Campinas, SP, Brazil. E-mail: Bgeloneze@aol.com