Accelerated protein digestion and amino acid absorption after Roux-en-Y gastric bypass.

BACKGROUND Roux-en-Y gastric bypass (RYGB) involves exclusion of major parts of the stomach and changes in admixture of gastro-pancreatic enzymes, which could have a major impact on protein digestion and amino acid absorption. OBJECTIVE We investigated the effect of RYGB on amino acid appearance in the systemic circulation from orally ingested protein and from endogenous release. DESIGN Nine obese glucose-tolerant subjects, with a mean body mass index (in kg/m(2)) of 39.2 (95% CI: 35.2, 43.3) and mean glycated hemoglobin of 5.3% (95% CI: 4.9%, 5.6%), were studied before and 3 mo after RYGB. Leucine and phenylalanine kinetics were determined under basal conditions and during 4 postprandial hours by intravenous infusions of [3,3,3-(2)H3]-leucine and [ring-(2)D5]-phenylalanine combined with ingestion of [1-(13)C]-leucine intrinsically labeled caseinate as the sole protein source of the meal. Changes in body composition were assessed by dual-energy X-ray absorptiometry. RESULTS After RYGB, basal plasma leucine concentration did not change, but marked changes were seen postprandially with 1.7-fold increased peak concentrations (before—mean: 217 μmol/L; 95% CI: 191, 243 μmol/L; 3 mo—mean: 377 μmol/L; 95% CI: 252, 502 μmol/L; P = 0.012) and 2-fold increased incremental AUC (before-mean: 4.1 mmol ∙ min/L; 95% CI: 2.7, 5.5 mmol ∙ min/L; 3 mo-mean: 9.5 mmol ∙ min/L; 95% CI: 4.9, 14.2 mmol ∙ min/L; P = 0.032). However, the postprandial hyperleucinemia was transient, and concentrations were below basal concentrations in the fourth postprandial hour. These concentration differences were mainly caused by changes in leucine appearance rate from orally ingested caseinate: peak rate increased nearly 3-fold [before—mean: 0.5 μmol/(kg fat-free mass ∙ min); 95% CI: 0.4, 0.5 μmol/(kg fat-free mass ∙ min); 3 mo—mean 1.4 μmol/(kg fat-free mass ∙ min); 95% CI: 0.8, 1.9 μmol/(kg fat-free mass ∙ min); P = 0.002], and time to peak was much shorter (before—mean: 173 min; 95% CI: 137, 209 min; 3 mo—mean: 65 min; 95% CI: 46, 84 min; P < 0.001). Only minor changes were seen in endogenous leucine release after RYGB. CONCLUSIONS RYGB accelerates caseinate digestion and amino acid absorption, resulting in faster and higher but more transient postprandial elevation of plasma amino acids. Changes are likely mediated by accelerated intestinal nutrient entry and clearly demonstrate that protein digestion is not impaired after RYGB. This trial was registered at clinicaltrials.gov as NCT01559792.

[1]  S. Nagata,et al.  Reprogramming of Intestinal Glucose Metabolism and Glycemic Control in Rats After Gastric Bypass , 2013 .

[2]  S. Madsbad,et al.  Fast pouch emptying, delayed small intestinal transit, and exaggerated gut hormone responses after Roux‐en‐Y gastric bypass , 2013, Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society.

[3]  J. McClung,et al.  Supplemental dietary leucine and the skeletal muscle anabolic response to essential amino acids. , 2011, Nutrition reviews.

[4]  B. Beaufrère,et al.  The digestion rate of protein is an independent regulating factor of postprandial protein retention. , 2001, American journal of physiology. Endocrinology and metabolism.

[5]  C. Newgard,et al.  Postprandial Metabolite Profiles Reveal Differential Nutrient Handling After Bariatric Surgery Compared With Matched Caloric Restriction , 2014, Annals of surgery.

[6]  A. Garg,et al.  Review: long-term impact of bariatric surgery on body weight, comorbidities, and nutritional status. , 2006, The Journal of clinical endocrinology and metabolism.

[7]  J. Holst,et al.  Gastric emptying, gastric secretion and enterogastrone response after administration of milk proteins or their peptide hydrolysates in humans , 2004, European journal of nutrition.

[8]  M. Suter,et al.  Effects of Gastric Bypass and Gastric Banding on Glucose Kinetics and Gut Hormone Release , 2008, Obesity.

[9]  J. Holst,et al.  Effects of gastric bypass surgery on glucose absorption and metabolism during a mixed meal in glucose-tolerant individuals , 2013, Diabetologia.

[10]  J. Holst,et al.  Hyperglucagonaemia analysed by glucagon sandwich ELISA: nonspecific interference or truly elevated levels? , 2014, Diabetologia.

[11]  B. Beaufrère,et al.  Influence of the protein digestion rate on protein turnover in young and elderly subjects. , 2002, The Journal of nutrition.

[12]  J. Holst,et al.  Changes in Gastrointestinal Hormone Responses, Insulin Sensitivity, and Beta-Cell Function Within 2 Weeks After Gastric Bypass in Non-diabetic Subjects , 2012, Obesity Surgery.

[13]  W. Saris,et al.  Plasma insulin responses after ingestion of different amino acid or protein mixtures with carbohydrate. , 2000, The American journal of clinical nutrition.

[14]  J. Holst,et al.  Early Enhancements of Hepatic and Later of Peripheral Insulin Sensitivity Combined With Increased Postprandial Insulin Secretion Contribute to Improved Glycemic Control After Roux-en-Y Gastric Bypass , 2014, Diabetes.

[15]  N. Abumrad,et al.  Body Composition and Energy Metabolism Following Roux‐en‐Y Gastric Bypass Surgery , 2010, Obesity.

[16]  D. Matthews,et al.  Leucine kinetics at graded intakes in young men: quantitative fate of dietary leucine. , 1988, The American journal of clinical nutrition.

[17]  J. Holst,et al.  Long-Term Effects of Bariatric Surgery on Meal Disposal and β-Cell Function in Diabetic and Nondiabetic Patients , 2013, Diabetes.

[18]  A. Lacy,et al.  Long-term dietary intake and nutritional deficiencies following sleeve gastrectomy or Roux-En-Y gastric bypass in a mediterranean population. , 2013, Journal of the Academy of Nutrition and Dietetics.

[19]  N. Kristensen,et al.  Whey and casein labeled with L-[1-13C]leucine and muscle protein synthesis: effect of resistance exercise and protein ingestion. , 2011, American journal of physiology. Endocrinology and metabolism.

[20]  Svati H Shah,et al.  A branched-chain amino acid-related metabolic signature that differentiates obese and lean humans and contributes to insulin resistance. , 2009, Cell metabolism.

[21]  H. Kuipers,et al.  Whey protein stimulates postprandial muscle protein accretion more effectively than do casein and casein hydrolysate in older men. , 2011, The American journal of clinical nutrition.

[22]  E. Volpi,et al.  Excess leucine intake enhances muscle anabolic signaling but not net protein anabolism in young men and women. , 2010, The Journal of nutrition.

[23]  Wim H M Saris,et al.  Amino acid ingestion strongly enhances insulin secretion in patients with long-term type 2 diabetes. , 2003, Diabetes care.

[24]  S. Klein,et al.  Gastric bypass and banding equally improve insulin sensitivity and β cell function. , 2012, The Journal of clinical investigation.

[25]  J. Holst,et al.  Incretin effect after oral amino acid ingestion in humans. , 2015, The Journal of clinical endocrinology and metabolism.

[26]  J. Holst,et al.  Exaggerated Glucagon-Like Peptide 1 Response Is Important for Improved β-Cell Function and Glucose Tolerance After Roux-en-Y Gastric Bypass in Patients With Type 2 Diabetes , 2013, Diabetes.

[27]  L. Groop,et al.  Effects of ingestion routes on hormonal and metabolic profiles in gastric-bypassed humans. , 2013, The Journal of clinical endocrinology and metabolism.

[28]  L. Sjöström Review of the key results from the Swedish Obese Subjects (SOS) trial – a prospective controlled intervention study of bariatric surgery , 2013, Journal of internal medicine.

[29]  E. Dimagno,et al.  Relations between pancreatic enzyme outputs and malabsorption in severe pancreatic insufficiency. , 1973, The New England journal of medicine.

[30]  W. Saris,et al.  Dietary protein digestion and absorption rates and the subsequent postprandial muscle protein synthetic response do not differ between young and elderly men. , 2009, The Journal of nutrition.

[31]  K. N. Bojsen-Møller Mechanisms of improved glycaemic control after Roux-en-Y gastric bypass. , 2015, Danish medical journal.

[32]  Elizabeth A. Odstrcil,et al.  The contribution of malabsorption to the reduction in net energy absorption after long-limb Roux-en-Y gastric bypass. , 2010, The American journal of clinical nutrition.

[33]  M. Wylezol,et al.  Nutrition management of the post-bariatric surgery patient. , 2015, Nutrition in clinical practice : official publication of the American Society for Parenteral and Enteral Nutrition.

[34]  L. Holm,et al.  Influence of Amino Acids, Dietary Protein, and Physical Activity on Muscle Mass Development in Humans , 2013, Nutrients.

[35]  K. Nair,et al.  Differential regulation of protein dynamics in splanchnic and skeletal muscle beds by insulin and amino acids in healthy human subjects. , 2003, Diabetes.

[36]  M. Jensen,et al.  Weight and type 2 diabetes after bariatric surgery: systematic review and meta-analysis. , 2009, The American journal of medicine.

[37]  J. Holst The physiology of glucagon-like peptide 1. , 2007, Physiological reviews.

[38]  B. Beaufrère,et al.  Slow and fast dietary proteins differently modulate postprandial protein accretion. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[39]  W. Saris,et al.  Ingestion of a protein hydrolysate is accompanied by an accelerated in vivo digestion and absorption rate when compared with its intact protein. , 2009, The American journal of clinical nutrition.

[40]  M. Bellon,et al.  Rapid gastric and intestinal transit is a major determinant of changes in blood glucose, intestinal hormones, glucose absorption and postprandial symptoms after gastric bypass , 2014, Obesity.

[41]  A. Lacy,et al.  Protein intake and lean tissue mass retention following bariatric surgery. , 2013, Clinical nutrition.

[42]  W. Millikan,et al.  Nutritional Consequences of Total Gastrectomy , 1975, Annals of surgery.

[43]  J. Dixon,et al.  Changes in fat-free mass during significant weight loss: a systematic review , 2007, International Journal of Obesity.

[44]  J. Gugenheim,et al.  Body composition, anthropometrics, energy expenditure, systemic inflammation, in premenopausal women 1 year after laparoscopic Roux-en-Y gastric bypass , 2014, Surgical Endoscopy.

[45]  J. Holst,et al.  Changes in glucose homeostasis after Roux-en-Y gastric bypass surgery for obesity at day three, two months, and one year after surgery: role of gut peptides. , 2011, The Journal of clinical endocrinology and metabolism.