Research Article: Metabolite Profiling Identifies Candidate Markers Reflecting the Clinical Adaptations Associated with Roux-en-Y Gastric Bypass Surgery

Date Published: November 19, 2009

Publisher: Public Library of Science

Author(s): David M. Mutch, Jens C. Fuhrmann, Dietrich Rein, Jan C. Wiemer, Jean-Luc Bouillot, Christine Poitou, Karine Clément, Jose A. L. Calbet. http://doi.org/10.1371/journal.pone.0007905

Abstract: Roux-en-Y gastric bypass (RYGB) surgery is associated with weight loss, improved insulin sensitivity and glucose homeostasis, and a reduction in co-morbidities such as diabetes and coronary heart disease. To generate further insight into the numerous metabolic adaptations associated with RYGB surgery, we profiled serum metabolites before and after gastric bypass surgery and integrated metabolite changes with clinical data.

Partial Text: Obesity is characterized by the accumulation of excess body fat to an extent that health is adversely affected via the development of co-morbidities. Due to a scarcity of validated and safe therapies, Roux-en-Y gastric bypass (RYGB) has become an increasingly effective treatment for severely obese patients [1], [2]. Following this procedure, patients experience a significant loss of weight; however, an unexpected and major outcome with gastric bypass surgery was that deaths related to coronary heart disease and diabetes were reduced by more than 50% and 90%, respectively [3]. Furthermore RYGB results in significant metabolic changes that lead to major improvements in blood glucose and insulin levels, insulin sensitivity and hormonal responses, as well as decreasing inflammatory markers [4], [5]. Lipid metabolism is also modified following the procedure, as demonstrated by decreases in total cholesterol and LDL-cholesterol, and increases in HDL-cholesterol [6]. Significant changes in the secretion of gastric and intestinal peptides such as glucagon-like peptide-1 (GLP-1), ghrelin, and peptide YY have also been demonstrated following RYGB [7], [8]. While a growing body of evidence supports the overall health benefits of bariatric surgery to treat morbid obesity, such a procedure is also associated with risks including mortality (<1%) and several complications such as venous thromboembolism, gallstone formation, and nutritional deficiencies [9]. Taken together, this procedure has a significant impact on a patient's whole-body metabolism and is therefore a unique model to understand the physiological and molecular mechanisms underlying the observed metabolic alterations. Gastric bypass surgery results in significant metabolic changes associated with weight loss, improved insulin sensitivity and glucose homeostasis, and a reduction in co-morbidities such as diabetes and coronary heart disease. A retrospective study in approximately 10,000 subjects who had undergone gastric bypass surgery revealed that mortality related to diabetes decreased by over 90%, leading to this medical procedure being proposed as a means to treat diabetes, even in subjects who are obese rather than morbidly obese [3]. As such, there is significant interest in unraveling the molecular adaptations underlying the improved insulin sensitivity seen post RYGB. We performed a global metabolite profiling analysis in morbidly obese female subjects before and after RYGB in order to generate new knowledge regarding the physiological and metabolic changes arising with this procedure. Source: http://doi.org/10.1371/journal.pone.0007905

 

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