Metabolite profiling identifies candidate markers reflecting the clinical adaptations associated with Roux-en-Y gastric bypass surgery.
BACKGROUND
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.


RESULTS
Serum metabolites were detected by gas and liquid chromatography-coupled mass spectrometry before, and 3 and 6 months after RYGB in morbidly obese female subjects (n = 14; BMI = 46.2+/-1.7). Subjects showed decreases in weight-related parameters and improvements in insulin sensitivity post surgery. The abundance of 48% (83 of 172) of the measured metabolites changed significantly within the first 3 months post RYGB (p<0.05), including sphingosines, unsaturated fatty acids, and branched chain amino acids. Dividing subjects into obese (n = 9) and obese/diabetic (n = 5) groups identified 8 metabolites that differed consistently at all time points and whose serum levels changed following RYGB: asparagine, lysophosphatidylcholine (C18:2), nervonic (C24:1) acid, p-Cresol sulfate, lactate, lycopene, glucose, and mannose. Changes in the aforementioned metabolites were integrated with clinical data for body mass index (BMI) and estimates for insulin resistance (HOMA-IR). Of these, nervonic acid was significantly and negatively correlated with HOMA-IR (p = 0.001, R = -0.55).


CONCLUSIONS
Global metabolite profiling in morbidly obese subjects after RYGB has provided new information regarding the considerable metabolic alterations associated with this surgical procedure. Integrating clinical measurements with metabolomics data is capable of identifying markers that reflect the metabolic adaptations following RYGB.
Mutch
David M
DM
Nutriomique U872 team 7, Institut National de la Santé et de la Recherche Médicale, Paris, France. dmutch@uoguelph.ca
Fuhrmann
Jens C
JC
Rein
Dietrich
D
Wiemer
Jan C
JC
Bouillot
Jean-Luc
JL
Poitou
Christine
C
Clément
Karine
K
D000596:Amino Acids / Q000378:metabolism; D015992:Body Mass Index; D002853:Chromatography, Liquid / Q000379:methods; D015897:Comorbidity; D048909:Diabetes Complications / Q000628:therapy; D004032:Diet; D005227:Fatty Acids / Q000378:metabolism; D005260:Female; D015390:Gastric Bypass / Q000379:methods*; D020869:Gene Expression Profiling; D005947:Glucose / Q000378:metabolism; D006801:Humans; D013058:Mass Spectrometry / Q000379:methods; D009765:Obesity / Q000097:blood / Q000150:complications / Q000601:surgery; D013110:Sphingosine / Q000378:metabolism
D000596:Amino Acids; D005227:Fatty Acids; D005947:Glucose; D013110:Sphingosine