At postoperative 12th week, ghrelin contents increased in the duodenum and pancreas, plasma ghrelin levels increased upon fasting, and ghrelin injection promoted feeding but not in earlier periods

At postoperative 12th week, ghrelin contents increased in the duodenum and pancreas, plasma ghrelin levels increased upon fasting, and ghrelin injection promoted feeding but not in earlier periods. feeding, BW, and thereby physical conditions in gastrectomized patients. == 1. Introduction == Ghrelin, a 28-amino acid peptide, is usually produced mainly in the stomach and to a lesser extent in the small intestine, pancreas, and hypothalamus and is the endogenous ligand for the growth hormone secretagogue receptor (GHS-R) [19]. Serine-3 of ghrelin is usually acylated with GNF-5 an octanoic acid, the process catalyzed by a recently discovered ghrelinO-acyltransferase (GOAT) [10,11]. The acylation is usually thought to be required for its biological activity [1], although desacyl ghrelin has been reported to exert several effects [12]. Administration of pharmacological doses of acylated ghrelin (= ghrelin) to intact animals increases food intake, induces body weight gain, and causes obesity [1318]. The orexigenic and body fat promoting properties of ghrelin and growth hormone (GH) secretagogue (GHS) are thought to be impartial of GH and mediated primarily by the hypothalamic neuropeptide Y (NPY) and agouti-related protein (AGRP) systems [1416,1922]. Although pharmacologic effects of ghrelin are well documented, physiological role of endogenous ghrelin is usually poorly understood. It has recently been reported that knockout of either the ghrelin gene or ghrelin receptor gene exerts no or minor effects on body weight and body composition [2325]. However, the lack of phenotypic changes in knockout mice might reflect compensatory mechanisms that are known to operate occasionally. In humans, gastrectomy results in loss of body weight of about 10% within the first six months after surgery, primarily due to reduced body fat [26]. In addition, gastrectomized patients often complain of loss of appetite, general fatigue, and in some cases impaired bone quality such as osteopenia and osteomalacia [9,27]. At present there are no satisfactory mechanistic explanation and treatment for any of these symptoms. The effects of gastrectomy on food intake and body composition have been poorly documented in rodents. Loss of ghrelin could be implicated in these symptoms, since as much as 80% of circulating ghrelin is usually lost following surgical removal of the glandular stomach or the acid producing part of the stomach in rats and humans [4,28,29]. In this study, we performed total gastrectomy in rats and examined whether the recovery from gastrectomy-associated anorexia depends on the circulating ghrelin level or other factors and studied temporal changes in the biosynthesis and orexigenic ability of ghrelin following gastrectomy. == 2. Materials and Methods == == 2.1. Animals and Gastrectomy == Male 4-week-old Wistar rats (SLC, Japan) were maintained on a 12-hour light/dark cycle and given conventional food and water for 2 weeks GNF-5 and not deprived of food GNF-5 before gastrectomy. They were operated at 6 weeks of age with body weight around 130180 g. Rats were anesthetized with an intraperitoneal injection of pentobarbital (40 mg/kg) and a median abdominal incision was made. After the stomach was separated from the greater and lesser omentum, the duodenal bulb was ligated and transected. After the left gastric artery was ligated, the esophagus was clamped above the esophagogastric junction and the stomach was resected. An end-to-side anastomosis between esophagus and jejunum at the 4-5 cm anal side from Treitz ligament was performed with 70 monofilament polyglyconate synthetic absorbable string (Maxon; Johnson & Johnson Inc. USA) using interrupted suture (Billroth II (B-II) reconstruction). On the other hand, jejunum was transected Rabbit Polyclonal to TSC22D1 at the 2-3 cm anal side from the Treitz ligament. Then, an end-to-side anastomosis between the esophagus and jejunum was performed with 70 Maxon using an interrupted suture. Jejunojejuno anastomosis was also done by end-to-side method (Roux-en-Y (R-Y) reconstruction). The abdominal wall and skin closure was made by 50 Nylon (Johnson & Johnson Inc. USA) in a running suture. After the operation, the rats were allowed only clear water without food for 3 days, dry milk from the 3rd day, and from the 7th day a conventional GNF-5 GNF-5 pellet diet with free access to water. The care of the animals was in accordance with our institutional guidelines. == 2.2. Measurements of Food Intake and Body Weights == After the operation, food intake for.