Wasif Abidi1,2, Eirini Nestoridi2,3, Henry Feldman4, Margaret Stefater2,3, Clary Clish5, Christopher C Thompson6,7, Nicholas Stylopoulos8,9,10. 1. Developmental Endoscopy Laboratory, Gastroenterology Division, Brigham and Women's Hospital, 75 Francis St, Thorn 1404, Boston, MA, 02115, USA. 2. Harvard Medical School, Boston, MA, USA. 3. Division of Endocrinology, CLS16066, Center for Basic and Translational Obesity Research, Boston Children's Hospital, 300 Longwood Avenue, Boston, MA, 02115, USA. 4. Institutional Centers for Clinical and Translational Research, Boston Children's Hospital, Boston, MA, USA. 5. Broad Institute of MIT and Harvard, Cambridge, MA, USA. 6. Developmental Endoscopy Laboratory, Gastroenterology Division, Brigham and Women's Hospital, 75 Francis St, Thorn 1404, Boston, MA, 02115, USA. ccthompson@bwh.harvard.edu. 7. Harvard Medical School, Boston, MA, USA. ccthompson@bwh.harvard.edu. 8. Harvard Medical School, Boston, MA, USA. nicholas.stylopoulos@childrens.harvard.edu. 9. Division of Endocrinology, CLS16066, Center for Basic and Translational Obesity Research, Boston Children's Hospital, 300 Longwood Avenue, Boston, MA, 02115, USA. nicholas.stylopoulos@childrens.harvard.edu. 10. Broad Institute of MIT and Harvard, Cambridge, MA, USA. nicholas.stylopoulos@childrens.harvard.edu.
Abstract
BACKGROUND: While Roux-en-Y gastric bypass (RYGB) is one of the most effective and durable treatment options for obesity and its comorbidities, it is complicated by long-term weight regain in over 20% of patients. AIMS: We sought to determine the metabolite signatures of serum samples of patients with weight regain (RYGB-WR) after RYGB and features distinguishing these patients from patients with sustained weight loss (RYGB-SWL). METHODS: We prospectively analyzed serum samples from 21 RYGB-WR patients, 14 RYGB-SWL patients, and 11 unoperated controls. The main outcome measure was their serum metabolite profile. RESULTS: Weight regain after RYGB was associated with a unique serum metabolomic fingerprint. Most of the statistically different metabolites were involved in amino acid metabolism, one-carbon metabolism, and related nucleotide metabolism. A principal component analysis identified groups of metabolites that correlate with weight regain. Specifically, weight regain was associated with lower serum levels of metabolites related to the serine, glycine and threonine pathway, phenylalanine metabolism, tricyclic acid cycle, alanine and glutamate metabolism, and higher levels of other amino acids. CONCLUSIONS: Weight regain after RYGB is associated with unique serum metabolite signatures. Metabolite profiling may eventually help us to identify markers that could differentiate the patients who will regain weight versus those who will likely sustain weight loss.
BACKGROUND: While Roux-en-Y gastric bypass (RYGB) is one of the most effective and durable treatment options for obesity and its comorbidities, it is complicated by long-term weight regain in over 20% of patients. AIMS: We sought to determine the metabolite signatures of serum samples of patients with weight regain (RYGB-WR) after RYGB and features distinguishing these patients from patients with sustained weight loss (RYGB-SWL). METHODS: We prospectively analyzed serum samples from 21 RYGB-WR patients, 14 RYGB-SWL patients, and 11 unoperated controls. The main outcome measure was their serum metabolite profile. RESULTS: Weight regain after RYGB was associated with a unique serum metabolomic fingerprint. Most of the statistically different metabolites were involved in amino acid metabolism, one-carbon metabolism, and related nucleotide metabolism. A principal component analysis identified groups of metabolites that correlate with weight regain. Specifically, weight regain was associated with lower serum levels of metabolites related to the serine, glycine and threonine pathway, phenylalanine metabolism, tricyclic acid cycle, alanine and glutamate metabolism, and higher levels of other amino acids. CONCLUSIONS: Weight regain after RYGB is associated with unique serum metabolite signatures. Metabolite profiling may eventually help us to identify markers that could differentiate the patients who will regain weight versus those who will likely sustain weight loss.
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