Clinical effects of ileal transposition in rats with diet-induced disglycemia

• Grant number: 11/05944-1
• Support Opportunities: Regular Research Grants
• Start date: September 01, 2011
• End date: August 31, 2013
• Field of knowledge: Health Sciences - Medicine - Surgery
• Principal Investigator: Joao Luiz Moreira Coutinho de Azevedo
• Grantee: Joao Luiz Moreira Coutinho de Azevedo
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil

Abstract

The clinical treatment of metabolic syndrome, principally that of glucose dysmetabolism (which is characterized by insulin resistance and type 2 diabetes mellitus), is known to be complex and lifelong, which is due to the progressive nature of the disease. Insulin resistance and diabetes mellitus are more commonly associated with obesity. However, the two conditions are not exclusive to the obese population, as evidenced by an increasingly higher incidence of type 2 diabetes mellitus among normal weight and overweight individuals. Insulin resistance is known to be the primary cause of cardiovascular disease in these individuals. There is currently a search for a surgical procedure that can effectively treat individuals (including non-obese individuals) with metabolic syndrome (principally type 2 diabetes mellitus). The gold standard for the treatment of morbid obesity is vertical banded gastric bypass, since this procedure achieves long-term weight loss and comorbidity control. However, in patients with glucose dysmetabolism without morbid obesity (i.e., mildly obese or overweight), ileal transposition-a technically simpler and more easily reversible procedure-can theoretically be an effective therapeutic alternative. There are reports in the literature regarding the use of ileal transposition in combination with sleeve gastrectomy. However, to date, ileal transposition has not been performed in isolation in humans. There are no reports of the use of ileal transposition in experimental models of diet-induced metabolic syndrome. Objectives: The overall objective of the present study is to evaluate the clinical effects of ileal transposition on metabolic syndrome. The specific objectives of the study, which will investigate rats with diet-induced obesity, are as follows: 1) to study the morphological and functional changes in L cells in a segment of the distal ileum that will be interposed with the proximal jejunum; 2) to study the structural changes in the small intestines of animals submitted to transposition of a segment of the distal ileum to a proximal position in the digestive tract; 3) to evaluate the endocrine pancreas after ileal transposition; and 4) to analyze changes in glucose and lipid metabolism after ileal transposition. Methods: Forty 12-week-old male Wistar rats (Rattus norvegicus albinus) of the WAB strain (heterogeneous) will be used. The rats will be divided into four groups of 10 animals: ileal transposition group, comprising animals on a high-calorie, high-fat diet; sham group, comprising sham-operated animals on a high-calorie, high-fat diet; control group 1, comprising animals that will be fed a high-calorie, high-fat diet and will not be submitted to surgical intervention; and control group 2, comprising animals that will be fed standard chow and will not be submitted to surgical intervention. The surgical procedures will be performed when animals are 20 weeks of age. The animals will be weighed, and blood samples will be collected under anesthesia when animals are aged 12 weeks, 20 weeks, and 28 weeks (postoperative week 8). In all animals, serum levels of glucose, insulin, triglycerides, total cholesterol, low-density lipoprotein, high-density lipoprotein, glucagon-like peptide-1, C-peptide, and glycosylated hemoglobin will be determined. The insulin tolerance test will be performed using the PRISMA software, and insulin resistance will be calculated using the homeostasis model assessment of insulin resistance. When rats are aged 20 weeks, two animals will be randomly distributed into the ileal transposition group and the sham group. All animals will be monitored for 8 postoperative weeks, after which they will be sacrificed. Epididymal and retroperitoneal fat pads will be collected and weighed on a precision balance, and the pancreas, the liver, and intestinal segments will be analyzed (anatomic pathology and immunohistochemistry). (AU)