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Roux-en-Y gastric bypass surgery improves hepatic glucose metabolism and reduces plasma kisspeptin levels in morbidly obese patients with type 2 diabetes.
Flynn CR, Albaugh VL, Tamboli RA, Gregory JM, Bosompem A, Sidani RM, Winnick JJ
(2020) Am J Physiol Gastrointest Liver Physiol 318: G370-G374
MeSH Terms: Adolescent, Adult, Anastomosis, Roux-en-Y, Blood Glucose, Diabetes Mellitus, Type 2, Female, Glucagon, Glucose, Humans, Insulin, Kisspeptins, Liver, Male, Middle Aged, Obesity, Morbid, Treatment Outcome, Young Adult
Show Abstract · Added November 12, 2019
Roux-en-Y gastric bypass surgery (RYGB) is known to improve whole-body glucose metabolism in patients with type 2 diabetes (T2D), although the mechanisms are not entirely clear and are likely multifactorial. The aim of this study was to assess fasting hepatic glucose metabolism and other markers of metabolic activity before and after RYGB in patients with and without T2D. Methods: Metabolic characteristics of patients who are obese with T2D were compared with those without the disease (non-T2D) before and 1 and 6 mo after RYGB. Fasting plasma insulin and the insulin:glucagon ratio were markedly reduced as early as 1 mo after RYGB in both patients with T2D and without T2D. Despite this reduction, endogenous glucose production and fasting plasma glucose levels were lower in both groups after RYGB, with the reductions being much larger in T2D. Plasma kisspeptin, an inhibitor of insulin secretion, was reduced only in T2D after surgery. Improved hepatic glucose metabolism and lower plasma kisspeptin in T2D after RYGB may link improved hepatic function with enhanced insulin responsiveness after surgery. Our manuscript is the first, to the best of our knowledge, to present data showing that Roux-en-Y gastric bypass surgery (RYGB) lowers fasting kisspeptin levels in patients who are obese with type 2 diabetes. This lowering of kisspeptin is important because it could link improvements in liver glucose metabolism after RYGB with increased insulin responsiveness also seen after surgery.
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17 MeSH Terms
Metabolic Effects of Bile Acids: Potential Role in Bariatric Surgery.
Flynn CR, Albaugh VL, Abumrad NN
(2019) Cell Mol Gastroenterol Hepatol 8: 235-246
MeSH Terms: Akkermansia, Animals, Bariatric Surgery, Bile Acids and Salts, Humans, Insulin Resistance, Obesity, Morbid, Receptors, Cytoplasmic and Nuclear, Signal Transduction, Verrucomicrobia
Show Abstract · Added December 17, 2019
Bariatric surgery is the most effective and durable treatment for morbid obesity, with an unexplained yet beneficial side effect of restoring insulin sensitivity and improving glycemia, often before weight loss is observed. Among the many contributing mechanisms often cited, the altered handling of intestinal bile acids is of considerable therapeutic interest. Here, we review a growing body of literature examining the metabolic effects of bile acids ranging from their physical roles in dietary fat handling within the intestine to their functions as endocrine and paracrine hormones in potentiating responses to bariatric surgery. The roles of 2 important bile acid receptors, Takeda G-protein coupled receptor (also known as G-protein coupled bile acid receptor) and farnesoid X receptor, are highlighted as is downstream signaling through glucagon-like polypeptide 1 and its cognate receptor. Additional improvements in other phenotypes and potential contributions of commensal gut bacteria, such as Akkermansia muciniphila, which are manifest after Roux-en-Y gastric bypass and other emulations, such as gallbladder bile diversion to the ileum, are also discussed.
Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.
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10 MeSH Terms
Comment on: greater curvature as a gastric pouch for sleeve gastrectomy: a novel bariatric procedure. Feasibility study in a canine model.
Albaugh VL
(2018) Surg Obes Relat Dis 14: 1820-1821
MeSH Terms: Animals, Bariatrics, Dogs, Feasibility Studies, Gastrectomy, Obesity, Morbid, Stomach
Added January 4, 2019
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1 Members
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7 MeSH Terms
Management of duodenal carcinoid tumors in the setting of morbid obesity.
Spann MD, Idrees K
(2017) Surg Obes Relat Dis 13: 1635-1637
MeSH Terms: Adult, Bariatric Surgery, Carcinoid Tumor, Duodenal Neoplasms, Duodenoscopy, Duodenum, Female, Gastrectomy, Humans, Incidental Findings, Lymph Node Excision, Obesity, Morbid, Preoperative Care
Added April 10, 2018
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1 Members
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13 MeSH Terms
What is the impact on the healthcare system if access to bariatric surgery is delayed?
Albaugh VL, English WJ
(2017) Surg Obes Relat Dis 13: 1627-1628
MeSH Terms: Bariatric Surgery, Delivery of Health Care, Humans, Obesity, Morbid
Added January 4, 2019
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1 Members
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4 MeSH Terms
Bile acids and bariatric surgery.
Albaugh VL, Banan B, Ajouz H, Abumrad NN, Flynn CR
(2017) Mol Aspects Med 56: 75-89
MeSH Terms: Animals, Bile Acids and Salts, Diabetes Mellitus, Type 2, Enterohepatic Circulation, Gastrectomy, Gastric Bypass, Gastrointestinal Microbiome, Gene Expression Regulation, Glucose, Homeostasis, Humans, Insulin Resistance, Obesity, Morbid, Receptors, Cytoplasmic and Nuclear, Receptors, G-Protein-Coupled, Rodentia, Signal Transduction
Show Abstract · Added June 6, 2017
Bariatric surgery, specifically Roux-en-Y gastric bypass (RYGB) and vertical sleeve gastrectomy (VSG), are the most effective and durable treatments for morbid obesity and potentially a viable treatment for type 2 diabetes (T2D). The resolution rate of T2D following these procedures is between 40 and 80% and far surpasses that achieved by medical management alone. The molecular basis for this improvement is not entirely understood, but has been attributed in part to the altered enterohepatic circulation of bile acids. In this review we highlight how bile acids potentially contribute to improved lipid and glucose homeostasis, insulin sensitivity and energy expenditure after these procedures. The impact of altered bile acid levels in enterohepatic circulation is also associated with changes in gut microflora, which may further contribute to some of these beneficial effects. We highlight the beneficial effects of experimental surgical procedures in rodents that alter bile secretory flow without gastric restriction or altering nutrient flow. This information suggests a role for bile acids beyond dietary fat emulsification in altering whole body glucose and lipid metabolism strongly, and also suggests emerging roles for the activation of the bile acid receptors farnesoid x receptor (FXR) and G-protein coupled bile acid receptor (TGR5) in these improvements. The limitations of rodent studies and the current state of our understanding is reviewed and the potential effects of bile acids mediating the short- and long-term metabolic improvements after bariatric surgery is critically examined.
Copyright © 2017 Elsevier Ltd. All rights reserved.
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17 MeSH Terms
Metabolic responses to exogenous ghrelin in obesity and early after Roux-en-Y gastric bypass in humans.
Tamboli RA, Antoun J, Sidani RM, Clements A, Harmata EE, Marks-Shulman P, Gaylinn BD, Williams B, Clements RH, Albaugh VL, Abumrad NN
(2017) Diabetes Obes Metab 19: 1267-1275
MeSH Terms: Acylation, Anti-Obesity Agents, Cohort Studies, Combined Modality Therapy, Cross-Over Studies, Energy Metabolism, Gastric Bypass, Ghrelin, Gluconeogenesis, Glucose Clamp Technique, Human Growth Hormone, Humans, Infusions, Intravenous, Insulin Resistance, Liver, Muscle, Skeletal, Obesity, Morbid, Pancreatic Polypeptide, Pancreatic Polypeptide-Secreting Cells, Pituitary Gland, Anterior, Postoperative Care, Preoperative Care, Protein Precursors, Single-Blind Method
Show Abstract · Added April 3, 2017
AIMS - Ghrelin is a gastric-derived hormone that stimulates growth hormone (GH) secretion and has a multi-faceted role in the regulation of energy homeostasis, including glucose metabolism. Circulating ghrelin concentrations are modulated in response to nutritional status, but responses to ghrelin in altered metabolic states are poorly understood. We investigated the metabolic effects of ghrelin in obesity and early after Roux-en-Y gastric bypass (RYGB).
MATERIALS AND METHODS - We assessed central and peripheral metabolic responses to acyl ghrelin infusion (1 pmol kg  min ) in healthy, lean subjects (n = 9) and non-diabetic, obese subjects (n = 9) before and 2 weeks after RYGB. Central responses were assessed by GH and pancreatic polypeptide (surrogate for vagal activity) secretion. Peripheral responses were assessed by hepatic and skeletal muscle insulin sensitivity during a hyperinsulinaemic-euglycaemic clamp.
RESULTS - Ghrelin-stimulated GH secretion was attenuated in obese subjects, but was restored by RYGB to a response similar to that of lean subjects. The heightened pancreatic polypeptide response to ghrelin infusion in the obese was attenuated after RYGB. Hepatic glucose production and hepatic insulin sensitivity were not altered by ghrelin infusion in RYGB subjects. Skeletal muscle insulin sensitivity was impaired to a similar degree in lean, obese and post-RYGB individuals in response to ghrelin infusion.
CONCLUSIONS - These data suggest that obesity is characterized by abnormal central, but not peripheral, responsiveness to ghrelin that can be restored early after RYGB before significant weight loss. Further work is necessary to fully elucidate the role of ghrelin in the metabolic changes that occur in obesity and following RYGB.
© 2017 John Wiley & Sons Ltd.
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24 MeSH Terms
Early Increases in Bile Acids Post Roux-en-Y Gastric Bypass Are Driven by Insulin-Sensitizing, Secondary Bile Acids.
Albaugh VL, Flynn CR, Cai S, Xiao Y, Tamboli RA, Abumrad NN
(2015) J Clin Endocrinol Metab 100: E1225-33
MeSH Terms: Adolescent, Adult, Bile Acids and Salts, Blood Glucose, Body Mass Index, Fasting, Female, Follow-Up Studies, Gastric Bypass, Humans, Insulin, Insulin Resistance, Male, Middle Aged, Obesity, Morbid, Treatment Outcome, Weight Loss, Young Adult
Show Abstract · Added August 26, 2015
CONTEXT - Roux-en-Y gastric bypass (RYGB) is the most effective treatment for morbid obesity and resolution of diabetes. Over the last decade, it has become well accepted that this resolution of diabetes occurs before significant weight loss; however, the mechanisms behind this effect remain unknown and could represent novel therapeutic targets for obesity and diabetes. Bile acids have been identified as putative mediators of these weight loss-independent effects.
OBJECTIVE - To identify the longitudinal changes in bile acids after RYGB, which may provide mechanistic insight into the weight loss-independent effects of RYGB.
DESIGN - Observational study before/after intervention.
SETTING - Academic medical center.
PATIENTS/PARTICIPANTS - Samples were collected from morbidly obese patients (n = 21) before and after RYGB.
INTERVENTION - RYGB.
MAIN OUTCOME MEASURES - Seventeen individual bile acid species were measured preoperatively and at 1, 6, 12, and 24 months postoperatively. Anthropometric, hormonal, and hyperinsulinemic-euglycemic clamp data were also examined to identify physiological parameters associated with bile acid changes.
RESULTS - Fasting total plasma bile acids increased after RYGB; however, increases were bimodal and were observed only at 1 (P < .05) and 24 months (P < .01). One-month increases were secondary to surges in ursodeoxycholic acid and its glycine and taurine conjugates, bacterially derived bile acids with putative insulin-sensitizing effects. Increases at 24 months were due to gradual rises in primary unconjugated bile acids as well as deoxycholic acid and its glycine conjugate. Plasma bile acid changes were not significantly associated with any anthropometric or hormonal measures, although hepatic insulin sensitivity was significantly improved at 1 month.
CONCLUSIONS - Overall findings suggest that bacterially derived bile acids may mediate the early improvements at 1 month after RYGB. Future studies should examine the changes in specific bile acid chemical species after bariatric procedures and bile acid-specific signaling changes.
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4 Members
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18 MeSH Terms
Metabolic adaptation following massive weight loss is related to the degree of energy imbalance and changes in circulating leptin.
Knuth ND, Johannsen DL, Tamboli RA, Marks-Shulman PA, Huizenga R, Chen KY, Abumrad NN, Ravussin E, Hall KD
(2014) Obesity (Silver Spring) 22: 2563-9
MeSH Terms: Adult, Basal Metabolism, Body Composition, Body Mass Index, Body Weight, Energy Metabolism, Female, Gastric Bypass, Humans, Leptin, Male, Middle Aged, Obesity, Morbid, Weight Loss
Show Abstract · Added January 20, 2015
OBJECTIVE - To measure changes in resting metabolic rate (RMR) and body composition in obese subjects following massive weight loss achieved via bariatric surgery or calorie restriction plus vigorous exercise.
METHODS - Body composition and RMR were measured in 13 pairs of obese subjects retrospectively matched for sex, body mass index, weight, and age who underwent either Roux-en-Y gastric bypass surgery (RYGB) or participated in "The Biggest Loser" weight loss competition (BLC).
RESULTS - Both groups had similar final weight loss (RYGB: 40.2 ± 12.7 kg, BLC: 48.8 ± 14.9 kg; P = 0.14); however, RYGB lost a larger proportion of their weight as fat-free mass (FFM) (RYGB: 30 ± 12%, BLC: 16 ± 8% [P < 0.01]). In both groups, RMR decreased significantly more than expected based on measured body composition changes. The magnitude of this metabolic adaptation was correlated with the degree of energy imbalance (r = 0.55, P = 0.004) and the decrease in circulating leptin (r = 0.47, P = 0.02).
CONCLUSIONS - Calorie restriction along with vigorous exercise in BLC participants resulted in preservation of FFM and greater metabolic adaption compared to RYGB subjects despite comparable weight loss. Metabolic adaptation was related to the degree of energy imbalance and the changes in circulating leptin.
© 2014 The Obesity Society.
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14 MeSH Terms
Changes in B-type natriuretic peptide and BMI following Roux-en-Y gastric bypass surgery.
Marney AM, Brown NJ, Tamboli R, Abumrad N
(2014) Diabetes Care 37: e70-1
MeSH Terms: Anastomosis, Roux-en-Y, Body Mass Index, Female, Gastric Bypass, Humans, Male, Natriuretic Peptide, Brain, Obesity, Morbid
Added February 19, 2015
0 Communities
3 Members
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8 MeSH Terms