Medical Student Research Fellowship for Summer 2012

Mentor:                       Vincent Aguirre
Department:               Medicine
Room number:           Y6.212
Mail Code:                 9151
Phone number:          8-0201
E-mail:                        Vincent.aguirre@utsouthwestern.edu

Project title:                Role of glucagon-like receptor 1 (GLP1) in effects of Roux-en-Y gastric bypass (RYGB) in mice

Human subjects IRB approved project number (where applicable):      

Animal subjects IRB approved project number (where applicable):       2009-0062

Project Type animal-based research

Brief Description of Project:  RYGB induces substantial weight loss in humans.  Understanding how and why this occurs on a molecular and anatomic level will enable the development of new therapies for weight loss that are efficacious for weight loss like bariatric surgery, but less-invasive and safer.  We have developed a mouse model of RYGB to investigate the anatomic and molecular mechanisms of this procedure.  In this project, we would like to test whether GLP1 is the beneficial effects of RYGB.  GLP1 is a peptide hormone released by specialized endocrine cells of the intestine.  RYGB induces secretion of GLP1, and GLP1 is believed to be involved in the beneficial effects of RYGB on both body weight and diabetes.  We aim to test this hypothesis by performing RYGB on transgenic mice that have been genetically-manipulated to LACK the cell-surface receptor for GLP1.  Absence of this receptor in mice renders animals unresponsive to endogenous GLP1.  If effects of RYGB on body weight and diabetes are mitigated in these mice, we will have determined that GLP1(R) is required for these effects of RYGB.  This would be a substantial advance in the expanding field of bariatric surgery in rodents.  The potential summer student will be closely involved in this project on many levels including care and metabolic characterization of post-surgical animals, including serial measurement of weight and food intake, body composition by NMR, assessment of energy expenditure in metabolic cages, and glucose homeostasis (fasting glycemia, glucose tolerance testing, insulin tolerance testing).

Project title:                Role of arcuate nucleus in effects of Roux-en-Y gastric bypass in mice

Human subjects IRB approved project number (where applicable):      

Animal subjects IRB approved project number (where applicable):       2009-0062

Project Type animal-based research

Brief Description of Project:  RYGB induces substantial weight loss in humans.  Understanding how and why this occurs on a molecular and anatomic level will enable the development of new therapies for weight loss that are efficacious for weight loss like bariatric surgery, but less-invasive and safer.  We have developed a mouse model of RYGB to investigate the anatomic and molecular mechanisms of this procedure.  In this project, we would like to test whether the arcuate nucleus, the area of the hypothalamus involved in body weight regulation, is involved in the effects of RYGB.  Animals that have been rendered obese by chemically-induced arcuate nucleus lesions will be subjected to RYGB to investigate the effect of RYGB on body weight and glucose homeostasis (diabetes) in this context.  We hope to determine if RYGB requires this area of the hypothalamus to induce its beneficial effects on body weight, diabetes, or both. The potential summer student will be closely involved in this project on many levels including care and metabolic characterization of post-surgical animals, including serial measurement of weight and food intake, body composition by NMR, assessment of energy expenditure in metabolic cages, and glucose homeostasis (fasting glycemia, glucose tolerance testing, insulin tolerance testing).

Previous Research Activities or Publications with Medical Students:

Previous summer students include Jason Cano, Stephen Howard, and Shashank Srivastiva.  Manuscripts involving their work are currently being prepared.