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Naseer F, Zhang SD, Miras AD, Redpath T, Martin M, Boyd A, Spence H, Pournaras DJ, Bodnar Z, Kerrigan D, le Roux CW, Livingstone MBE, Price RK. Metabolic adaptation following gastric bypass surgery: results from a 2-year observational study. Int J Obes (Lond) 2024; 48:1577-1586. [PMID: 39227457 PMCID: PMC11502489 DOI: 10.1038/s41366-024-01585-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/21/2023] [Revised: 07/01/2024] [Accepted: 07/08/2024] [Indexed: 09/05/2024]
Abstract
BACKGROUND/OBJECTIVES Metabolic adaptation is the lowering of basal metabolic rate (BMR) beyond what is predicted from changes in fat mass (FM) and fat-free mass (FFM) and may hamper weight-loss progression. It is unclear whether metabolic adaptation occurs following gastric bypass surgery (GBP) and if it persists. The aim of this study was to evaluate the reduction in BMR that is not explained by changes in body composition in patients following GBP compared to a weight-stable comparator group. SUBJECTS Thirty-one patients [77.4% female; mean BMI 45.5(SD 7.0) kg/m2; age 47.4(11.6)y] who underwent GBP, and 32 time-matched comparators [50% female; BMI 27.2(4.6) kg/m2; age 41.8(13.6)y) were evaluated at 1-month pre-surgery, 3-, 12- and 24-months post-surgery. METHODS BMR was measured under standardised residential conditions using indirect calorimetry and body composition using DXA. Linear regression analyses assessed metabolic adaptation post-surgery. RESULTS After surgery, patients lost a quarter of their body weight [-25.6%(1.8%); p < 0.0001] consisting mainly of FM (4:1 FM to FFM loss ratio) at 24-months post-surgery. Absolute BMR (MJ/d) reduced by 25.7% at 24-months post-surgery with values becoming similar to the comparator group from 3-months post-surgery. Positive associations were observed between changes in BMR and changes in FFM and FM (P < 0.03). Metabolic adaptation was present in patients during the 1) rapid weight loss phase (6.9 kg/month at 3-months post-surgery) (p = 0.011), 2) slower weight loss phase (1.6 kg/month from 3 to 12-months post-surgery) (p < 0.0001), and, 3) weight maintenance phase (24-months post-surgery) (p = 0.00073). However, the degree of metabolic adaptation observed in GBP patients was similar to the weight-stable comparator group (no metabolic adaptation) from 12-months post-surgery onwards (3-months; p = 0.01, 12-months; p = 0.26, 24-months post-surgery; p = 0.70). CONCLUSION These results suggest that there is a potential biological mechanism of surgery that attenuates the expected postoperative downregulation in BMR thus helping GBP patients maintain weight loss.
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Affiliation(s)
- Fathimath Naseer
- Nutrition Innovation Centre for Food and Health (NICHE), Ulster University, Coleraine, BT52 1SA, United Kingdom
| | - Shu-Dong Zhang
- School of Medicine, Ulster University, Londonderry, BT48 7JL, United Kingdom
| | - Alexander D Miras
- School of Medicine, Ulster University, Londonderry, BT48 7JL, United Kingdom
| | - Tamsyn Redpath
- Nutrition Innovation Centre for Food and Health (NICHE), Ulster University, Coleraine, BT52 1SA, United Kingdom
| | - Melanie Martin
- Nutrition Innovation Centre for Food and Health (NICHE), Ulster University, Coleraine, BT52 1SA, United Kingdom
| | - Adele Boyd
- Nutrition Innovation Centre for Food and Health (NICHE), Ulster University, Coleraine, BT52 1SA, United Kingdom
| | - Heather Spence
- Nutrition Innovation Centre for Food and Health (NICHE), Ulster University, Coleraine, BT52 1SA, United Kingdom
| | - Dimitri J Pournaras
- Department of Bariatric and Metabolic Surgery, North Bristol NHS Trust, Southmead Hospital, Bristol, BS10 5NB, England
| | - Zsolt Bodnar
- Department of Surgery, Letterkenny University Hospital, Donegal, Ireland
| | - David Kerrigan
- Phoenix Health, 17E-F Telford Court, Chester, CH1 6LT, England
| | - Carel W le Roux
- Diabetes Complications Research Centre, Conway Institute, University College Dublin, Dublin, Ireland
| | - M Barbara E Livingstone
- Nutrition Innovation Centre for Food and Health (NICHE), Ulster University, Coleraine, BT52 1SA, United Kingdom
| | - Ruth K Price
- Nutrition Innovation Centre for Food and Health (NICHE), Ulster University, Coleraine, BT52 1SA, United Kingdom.
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Falkenhain K, Martin CK, Ravussin E, Redman LM. Energy expenditure, metabolic adaptation, physical activity and energy intake following weight loss: comparison between bariatric surgery and low-calorie diet. Eur J Clin Nutr 2024:10.1038/s41430-024-01523-8. [PMID: 39478234 PMCID: PMC12041307 DOI: 10.1038/s41430-024-01523-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2024] [Revised: 10/08/2024] [Accepted: 10/09/2024] [Indexed: 03/20/2025]
Abstract
OBJECTIVE Bariatric surgery remains the most effective treatment to achieve substantial weight loss; however, total daily energy expenditure and physical activity changes in response to such interventions have been seldom explored. METHODS In this prospective observational study, total daily energy expenditure (TDEE) using doubly labeled water and physical activity (SenseWear armband) was assessed in 17 females (mean ± SD: 48.6 ± 9.7 kg/m2, 43 ± 12 years) at baseline and 8 and 52 weeks following either bariatric surgery (BSG, N = 9) or a low-calorie diet (LCD, N = 8). Energy intake was assessed using the intake-balance method. RESULTS After 8 weeks, weight loss was 16.0 ± 3.5 kg and TDEE decreased by 552 ± 319 kcal/d in BSG (P < 0.001) compared to 8.8 ± 3.4 kg and 256 ± 239 kcal/d in LCD (P < 0.05). After 52 weeks, weight loss was 44.3 ± 16.4 kg and TDEE decreased by 583 ± 418 kcal/d (P < 0.001), compared to 4.3 ± 6.7 kg and 84 ± 285 kcal/d in LCD (P > 0.05). TDEE was lower than predicted in BSG at 8 (P = 0.03) but not 52 weeks (P = 0.77). There was no evidence of metabolic adaptation in LCD. Average daily energy intake in BSG was 1403 ± 245 kcal/d compared to 2545 ± 398 kcal/d in LCD (P < 0.001). In BSG, step count and physical activity minutes were increased at 52 weeks compared to baseline (P = 0.03), whereas no significant changes were observed in LCD. CONCLUSION Bariatric surgery-induced weight loss decreased TDEE at 8 weeks and 1 year, resulting in metabolic adaptation after 8 weeks that was reversed at 1 year. These changes were accompanied by an increase in physical activity.
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Affiliation(s)
- Kaja Falkenhain
- Pennington Biomedical Research Center, Baton Rouge, Louisiana, USA
| | - Corby K Martin
- Pennington Biomedical Research Center, Baton Rouge, Louisiana, USA
| | - Eric Ravussin
- Pennington Biomedical Research Center, Baton Rouge, Louisiana, USA
| | - Leanne M Redman
- Pennington Biomedical Research Center, Baton Rouge, Louisiana, USA.
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Simoneau M, McKay B, Brooks E, Doucet É, Baillot A. Gut peptides before and following Roux-En-Y gastric bypass: A systematic review and meta-analysis. Obes Rev 2024; 25:e13702. [PMID: 38327045 DOI: 10.1111/obr.13702] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/22/2022] [Revised: 12/20/2023] [Accepted: 12/21/2023] [Indexed: 02/09/2024]
Abstract
A systematic search was conducted in Medline Ovid, Embase, Scopus, and Cochrane Central Register of Controlled Trials up until March 2021 following PRISMA guidelines. Studies included evaluated ghrelin, GLP-1, PYY or appetite sensation via visual analogue scales (VASs) before and after Roux-en-Y gastric bypass (RYGB) in adults. A multilevel model with random effects for study and follow-up time points nested in study was fit to the data. The model included kcal consumption as a covariate and time points as moderators. Among the 2559 articles identified, k = 47 were included, among which k = 19 evaluated ghrelin, k = 40 GLP-1, k = 22 PYY, and k = 8 appetite sensation. Our results indicate that fasting ghrelin levels are decreased 2 weeks post-RYGB (p = 0.005) but do not differ from baseline from 6 weeks to 1-year post-RYGB. Postprandial ghrelin and fasting GLP-1 levels were not different from pre-surgical values. Postprandial levels of GLP-1 increased significantly from 1 week (p < 0.001) to 2 years post-RYGB (p < 0.01) compared with pre-RYGB. Fasting PYY increased at 6 months (p = 0.034) and 1 year (p = 0.029) post-surgery; also, postprandial levels increased up to 1 year (p < 0.01). Insufficient data on appetite sensation were available to be meta-analyzed.
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Affiliation(s)
- Mylène Simoneau
- School of Human Kinetics, University of Ottawa, Ottawa, Ontario, Canada
| | - Brad McKay
- Department of kinesiology, University of McMaster, Hamilton, Ontario, Canada
| | - Emma Brooks
- School of Human Kinetics, University of Ottawa, Ottawa, Ontario, Canada
| | - Éric Doucet
- School of Human Kinetics, University of Ottawa, Ottawa, Ontario, Canada
| | - Aurélie Baillot
- Department of nursing, University of Québec en Outaouais, Gatineau, Quebec, Canada
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Nymo S, Lundanes J, Eriksen K, Aukan M, Rehfeld JF, Holst JJ, Johnsen G, Græslie H, Kulseng B, Sandvik J, Martins C. Suboptimal Weight Loss 13 Years After Roux-en-Y Gastric Bypass Is Associated with Blunted Appetite Response. Obes Surg 2024; 34:592-601. [PMID: 38159146 PMCID: PMC10811108 DOI: 10.1007/s11695-023-07028-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2023] [Revised: 12/20/2023] [Accepted: 12/20/2023] [Indexed: 01/03/2024]
Abstract
PURPOSE Bariatric surgery remains the most efficient treatment to achieve a sustained weight loss. However, a large proportion of patients experience suboptimal weight loss (SWL). The exact mechanisms involved remain to be fully elucidated, but the homeostatic appetite control system seems to be involved. The aim of this study was, therefore, to compare the plasma concentration of gastrointestinal hormones, and appetite ratings, between those experiencing SWL and optimal weight loss (OWL) after Roux-en-Y gastric bypass (RYGB). MATERIALS AND METHODS Fifty participants from the Bariatric Surgery Observation Study (BAROBS) experiencing either SWL or OWL (< or ≥ 50% of excess weight loss (EWL), respectively) > 13 years post-RYGB were compared to 25 non-surgical controls. Plasma concentrations of acylated ghrelin (AG), total glucagon-like peptide-1 (GLP-1), total peptide YY (PYY), cholecystokinin (CCK), and subjective ratings of hunger, fullness, desire to eat (DTE), and prospective food consumption (PFC) were assessed in the fasting and postprandial (area under the curve (AUC)) states. RESULTS Those experiencing OWL presented with higher basal AG and GLP-1 iAUC, and lower AG iAUC compared with SWL and controls. Additionally, both bariatric groups presented with higher PYY and CCK iAUC compared to controls. PFC tAUC was also lower in OWL compared to the SWL group. Total weight loss was positively correlated with GLP-1 tAUC and negatively correlated with fasting and tAUC DTE and PFC tAUC. CONCLUSIONS SWL > 13 years post-RYGB is associated with lower basal ghrelin, as well as a weaker satiety response to a meal. Future studies should investigate the causality of these associations.
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Affiliation(s)
- Siren Nymo
- Obesity Research Group, Department of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology (NTNU), Forsyningssenteret, Prinsesse Kristinas gate 5, 7030, Trondheim, Norway.
- Centre for Obesity and Innovation (ObeCe), Clinic of Surgery, St. Olav University Hospital, Trondheim, Norway.
- Nord-Trøndelag Hospital Trust, Clinic of Surgery, Namsos Hospital, Namsos, Norway.
| | - Julianne Lundanes
- Obesity Research Group, Department of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology (NTNU), Forsyningssenteret, Prinsesse Kristinas gate 5, 7030, Trondheim, Norway
- Nord-Trøndelag Hospital Trust, Clinic of Surgery, Namsos Hospital, Namsos, Norway
| | - Kevin Eriksen
- Obesity Research Group, Department of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology (NTNU), Forsyningssenteret, Prinsesse Kristinas gate 5, 7030, Trondheim, Norway
| | - Marthe Aukan
- Obesity Research Group, Department of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology (NTNU), Forsyningssenteret, Prinsesse Kristinas gate 5, 7030, Trondheim, Norway
- Centre for Obesity and Innovation (ObeCe), Clinic of Surgery, St. Olav University Hospital, Trondheim, Norway
| | - Jens Frederik Rehfeld
- Department of Clinical Biochemistry, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
| | - Jens Juul Holst
- NNF Center for Basic Metabolic Research and Department of Biomedical Sciences, The Panum Institute, University of Copenhagen, Copenhagen, Denmark
| | - Gjermund Johnsen
- Obesity Research Group, Department of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology (NTNU), Forsyningssenteret, Prinsesse Kristinas gate 5, 7030, Trondheim, Norway
| | - Hallvard Græslie
- Nord-Trøndelag Hospital Trust, Clinic of Surgery, Namsos Hospital, Namsos, Norway
| | - Bård Kulseng
- Obesity Research Group, Department of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology (NTNU), Forsyningssenteret, Prinsesse Kristinas gate 5, 7030, Trondheim, Norway
- Centre for Obesity and Innovation (ObeCe), Clinic of Surgery, St. Olav University Hospital, Trondheim, Norway
| | - Jorunn Sandvik
- Obesity Research Group, Department of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology (NTNU), Forsyningssenteret, Prinsesse Kristinas gate 5, 7030, Trondheim, Norway
- Centre for Obesity and Innovation (ObeCe), Clinic of Surgery, St. Olav University Hospital, Trondheim, Norway
- Møre and Romsdal Hospital Trust, Clinic of Surgery, Ålesund Hospital, Ålesund, Norway
| | - Catia Martins
- Obesity Research Group, Department of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology (NTNU), Forsyningssenteret, Prinsesse Kristinas gate 5, 7030, Trondheim, Norway
- Centre for Obesity and Innovation (ObeCe), Clinic of Surgery, St. Olav University Hospital, Trondheim, Norway
- Department of Nutrition Sciences, University of Alabama at Birmingham (UAB), Birmingham, AL, USA
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Alabduljabbar K, Bonanos E, Miras AD, le Roux CW. Mechanisms of Action of Bariatric Surgery on Body Weight Regulation. Gastroenterol Clin North Am 2023; 52:691-705. [PMID: 37919021 DOI: 10.1016/j.gtc.2023.08.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2023]
Abstract
Bariatric surgery is an effective treatment modality for obesity and obesity-associated complications. Weight loss after bariatric surgery was initially attributed to anatomic restriction or reduced energy absorption, but now it is understood that surgery treats obesity by influencing the subcortical areas of the brain to lower adipose tissue mass. There are three major phases of this process: initially the weight loss phase, followed by a phase where weight loss is maintained, and in a subset of patients a phase where weight is regained. These phases are characterized by altered appetitive behavior together with changes in energy expenditure. The mechanisms associated with the rearrangement of the gastrointestinal tract include central appetite control, release of gut peptides, change in microbiota and bile acids. However, the exact combination and timing of signals remain largely unknown.
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Affiliation(s)
- Khaled Alabduljabbar
- Diabetes Complications Research Centre, Conway Institute, University College Dublin, Dublin, Ireland; Department of Family Medicine and Polyclinics, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia.
| | | | | | - Carel W le Roux
- Diabetes Complications Research Centre, Conway Institute, University College Dublin, Dublin, Ireland.
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Bojsen-Møller KN, Svane MS, Martinussen C, Dirksen C, Jørgensen NB, Jensen JEB, Jensen CZ, Torekov SS, Kristiansen VB, Rehfeld JF, Bork-Jensen J, Grarup N, Hansen T, Hartmann B, Holst JJ, Madsbad S. Primary weight loss failure after Roux-en-Y gastric bypass is characterized by impaired gut-hormone mediated regulation of food intake. Int J Obes (Lond) 2023; 47:1143-1151. [PMID: 37653071 PMCID: PMC10599997 DOI: 10.1038/s41366-023-01372-8] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/02/2023] [Revised: 08/11/2023] [Accepted: 08/17/2023] [Indexed: 09/02/2023]
Abstract
BACKGROUND/OBJECTIVES After Roux-en-Y gastric bypass (RYGB) a subset of patients never obtain excess BMI loss (EBMIL) > 50% and are categorized as having primary weight loss (WL) failure. We hypothesized that postprandial concentrations of glucagon-like peptide 1 (GLP-1) and peptide YY (PYY) would be lower in patients with primary WL failure compared with patients with successfully maintained WL. Furthermore, that inhibition of gut hormone secretions would increase ad libitum food intake less in patients with primary WL failure. SUBJECTS/METHODS Twenty women with primary WL failure (LowEBMIL < 50%) were individually matched to twenty women with successful WL (HighEBMIL > 60%) on age, preoperative BMI and time from RYGB. On separate days performed in a random order, patient-blinded subcutaneous injections of octreotide or saline (placebo) were followed by a fixed breakfast and an ad libitum lunch with blood sampling for appetite regulating hormones and Visual-Analogue-Scale (VAS)-scoring of hunger/satiety. Furthermore, participants underwent gene variant analysis for GLP-1, PYY and their receptors, indirect calorimetry, dual-energy X-ray absorptiometry (DXA)-scans, 4-days at-home food registration and 14-days step counting. RESULTS On placebo days, postprandial GLP-1, PYY and cholecystokinin (CCK) concentrations were similar between groups after breakfast. Fasting ghrelin was lower in LowEBMIL, but the postprandial suppression was similar. LowEBMIL had lower satiety VAS-scores and less suppression of hunger VAS-scores. Gene variants did not differ between groups. Octreotide diminished GLP-1, PYY, CCK and ghrelin concentrations in both groups. Octreotide did not affect ad libitum food intake in LowEBMIL (-1% [-13, 12], mean [95%CI]), while food intake increased in HighEBMIL (+23% [2,44]). CONCLUSIONS Primary WL failure after RYGB was not characterized by impaired secretions of appetite regulating gut hormones. Interestingly, inhibition of gut hormone secretions with octreotide only increased food intake in patients with successful WL post-RYGB. Thus, an impaired central anorectic response to gut hormones may contribute to primary WL failure after RYGB.
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Affiliation(s)
- Kirstine Nyvold Bojsen-Møller
- Dept. of Endocrinology, Copenhagen University Hospital Hvidovre, Copenhagen, Denmark.
- Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark.
| | - Maria Saur Svane
- Dept. of Endocrinology, Copenhagen University Hospital Hvidovre, Copenhagen, Denmark
- Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark
| | - Christoffer Martinussen
- Dept. of Endocrinology, Copenhagen University Hospital Hvidovre, Copenhagen, Denmark
- Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark
| | - Carsten Dirksen
- Dept. of Endocrinology, Copenhagen University Hospital Hvidovre, Copenhagen, Denmark
- Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark
- Dept. of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark
| | - Nils Bruun Jørgensen
- Dept. of Endocrinology, Copenhagen University Hospital Hvidovre, Copenhagen, Denmark
- Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark
| | - Jens-Erik Beck Jensen
- Dept. of Endocrinology, Copenhagen University Hospital Hvidovre, Copenhagen, Denmark
- Dept. of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark
| | - Christian Zinck Jensen
- Dept. of Endocrinology, Copenhagen University Hospital Hvidovre, Copenhagen, Denmark
- Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark
| | - Signe Sørensen Torekov
- Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark
- Dept. of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark
| | | | | | - Jette Bork-Jensen
- Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark
| | - Niels Grarup
- Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark
| | - Torben Hansen
- Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark
| | - Bolette Hartmann
- Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark
- Dept. of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Jens Juul Holst
- Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark
- Dept. of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Sten Madsbad
- Dept. of Endocrinology, Copenhagen University Hospital Hvidovre, Copenhagen, Denmark
- Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark
- Dept. of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark
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Lim JJ, Liu Y, Lu LW, Sequeira IR, Poppitt SD. No Evidence That Circulating GLP-1 or PYY Are Associated with Increased Satiety during Low Energy Diet-Induced Weight Loss: Modelling Biomarkers of Appetite. Nutrients 2023; 15:nu15102399. [PMID: 37242282 DOI: 10.3390/nu15102399] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2023] [Revised: 04/04/2023] [Accepted: 05/16/2023] [Indexed: 05/28/2023] Open
Abstract
Bariatric surgery and pharmacology treatments increase circulating glucagon-like peptide-1 (GLP-1) and peptide YY (PYY), in turn promoting satiety and body weight (BW) loss. However, the utility of GLP-1 and PYY in predicting appetite response during dietary interventions remains unsubstantiated. This study investigated whether the decrease in hunger observed following low energy diet (LED)-induced weight loss was associated with increased circulating 'satiety peptides', and/or associated changes in glucose, glucoregulatory peptides or amino acids (AAs). In total, 121 women with obesity underwent an 8-week LED intervention, of which 32 completed an appetite assessment via a preload challenge at both Week 0 and Week 8, and are reported here. Visual analogue scales (VAS) were administered to assess appetite-related responses, and blood samples were collected over 210 min post-preload. The area under the curve (AUC0-210), incremental AUC (iAUC0-210), and change from Week 0 to Week 8 (∆) were calculated. Multiple linear regression was used to test the association between VAS-appetite responses and blood biomarkers. Mean (±SEM) BW loss was 8.4 ± 0.5 kg (-8%). Unexpectedly, the decrease in ∆AUC0-210 hunger was best associated with decreased ∆AUC0-210 GLP-1, GIP, and valine (p < 0.05, all), and increased ∆AUC0-210 glycine and proline (p < 0.05, both). The majority of associations remained significant after adjusting for BW and fat-free mass loss. There was no evidence that changes in circulating GLP-1 or PYY were predictive of changes in appetite-related responses. The modelling suggested that other putative blood biomarkers of appetite, such as AAs, should be further investigated in future larger longitudinal dietary studies.
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Affiliation(s)
- Jia Jiet Lim
- Human Nutrition Unit, School of Biological Sciences, University of Auckland, Auckland 1024, New Zealand
- Riddet Institute, Palmerston North 4442, New Zealand
| | - Yutong Liu
- Human Nutrition Unit, School of Biological Sciences, University of Auckland, Auckland 1024, New Zealand
- Department of Medicine, University of Auckland, Auckland 1010, New Zealand
| | - Louise W Lu
- Human Nutrition Unit, School of Biological Sciences, University of Auckland, Auckland 1024, New Zealand
- High-Value Nutrition National Science Challenge, Auckland 1010, New Zealand
| | - Ivana R Sequeira
- Human Nutrition Unit, School of Biological Sciences, University of Auckland, Auckland 1024, New Zealand
- High-Value Nutrition National Science Challenge, Auckland 1010, New Zealand
| | - Sally D Poppitt
- Human Nutrition Unit, School of Biological Sciences, University of Auckland, Auckland 1024, New Zealand
- Riddet Institute, Palmerston North 4442, New Zealand
- Department of Medicine, University of Auckland, Auckland 1010, New Zealand
- High-Value Nutrition National Science Challenge, Auckland 1010, New Zealand
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Aukan MI, Skårvold S, Brandsaeter IØ, Rehfeld JF, Holst JJ, Nymo S, Coutinho S, Martins C. Gastrointestinal hormones and appetite ratings after weight loss induced by diet or bariatric surgery. Obesity (Silver Spring) 2023; 31:399-411. [PMID: 36536482 PMCID: PMC10108040 DOI: 10.1002/oby.23655] [Citation(s) in RCA: 15] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/02/2022] [Revised: 11/08/2022] [Accepted: 11/10/2022] [Indexed: 12/24/2022]
Abstract
OBJECTIVE The aim of this study was to compare changes in gastrointestinal hormones and appetite ratings after a similar weight loss induced by a very low-energy diet alone or in combination with sleeve gastrectomy (SG) or Roux-en-Y gastric bypass (RYGB). METHODS Patients with severe obesity scheduled for SG (n = 15) and RYGB (n = 14) and 15 controls (very low-energy diet alone) were recruited. Body weight/composition, plasma concentrations of ß-hydroxybutyric acid, acylated ghrelin, total glucagon-like peptide-1, total peptide YY, cholecystokinin, and ratings of hunger, fullness, desire to eat, and prospective food consumption were measured pre- and postprandially, before and after 10 weeks of intervention. RESULTS Changes in body weight/composition and level of ketosis were similar across groups. In SG and RYGB, basal and postprandial acylated ghrelin declined, and postprandial glucagon-like peptide-1 increased, both significantly more compared with controls. Postprandial peptide YY increased in all groups. Overall, postprandial hunger decreased, and postprandial fullness increased. But ratings of desire to eat and prospective food consumption were more favorable after both surgeries compared with controls. CONCLUSIONS Weight loss with SG and RYGB leads to more favorable changes in gastrointestinal hormones compared with diet alone, although ratings of appetite were reduced across all groups.
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Affiliation(s)
- Marthe Isaksen Aukan
- Obesity Research Group, Department of Clinical and Molecular Medicine, Faculty of Medicine, Norwegian University of Science and Technology (NTNU), Trondheim, Norway
- Centre of Obesity and Innovation (ObeCe), Clinic of Surgery, St. Olav University Hospital, Trondheim, Norway
| | - Silje Skårvold
- Obesity Research Group, Department of Clinical and Molecular Medicine, Faculty of Medicine, Norwegian University of Science and Technology (NTNU), Trondheim, Norway
| | - Ingrid Øfsti Brandsaeter
- Obesity Research Group, Department of Clinical and Molecular Medicine, Faculty of Medicine, Norwegian University of Science and Technology (NTNU), Trondheim, Norway
| | - Jens Frederik Rehfeld
- Department of Clinical Biochemistry, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
| | - Jens Juul Holst
- The NovoNordisk Center for Basic Metabolic Research and Department of Biomedical Sciences, The Panum Institute, University of Copenhagen, Copenhagen, Denmark
| | - Siren Nymo
- Obesity Research Group, Department of Clinical and Molecular Medicine, Faculty of Medicine, Norwegian University of Science and Technology (NTNU), Trondheim, Norway
- Centre of Obesity and Innovation (ObeCe), Clinic of Surgery, St. Olav University Hospital, Trondheim, Norway
- Nord-Trøndelag Hospital Trust, Clinic of Surgery, Namsos Hospital, Namsos, Norway
| | - Silvia Coutinho
- Obesity Research Group, Department of Clinical and Molecular Medicine, Faculty of Medicine, Norwegian University of Science and Technology (NTNU), Trondheim, Norway
- Department of Public Health Nutrition at the Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo, Oslo, Norway
| | - Catia Martins
- Obesity Research Group, Department of Clinical and Molecular Medicine, Faculty of Medicine, Norwegian University of Science and Technology (NTNU), Trondheim, Norway
- Centre of Obesity and Innovation (ObeCe), Clinic of Surgery, St. Olav University Hospital, Trondheim, Norway
- Department of Nutrition Sciences, University of Alabama at Birmingham, Birmingham, Alabama, USA
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9
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Albaugh VL, He Y, Münzberg H, Morrison CD, Yu S, Berthoud HR. Regulation of body weight: Lessons learned from bariatric surgery. Mol Metab 2023; 68:101517. [PMID: 35644477 PMCID: PMC9938317 DOI: 10.1016/j.molmet.2022.101517] [Citation(s) in RCA: 39] [Impact Index Per Article: 19.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/12/2021] [Revised: 05/04/2022] [Accepted: 05/21/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Bariatric or weight loss surgery is currently the most effective treatment for obesity and metabolic disease. Unlike dieting and pharmacology, its beneficial effects are sustained over decades in most patients, and mortality is among the lowest for major surgery. Because there are not nearly enough surgeons to implement bariatric surgery on a global scale, intensive research efforts have begun to identify its mechanisms of action on a molecular level in order to replace surgery with targeted behavioral or pharmacological treatments. To date, however, there is no consensus as to the critical mechanisms involved. SCOPE OF REVIEW The purpose of this non-systematic review is to evaluate the existing evidence for specific molecular and inter-organ signaling pathways that play major roles in bariatric surgery-induced weight loss and metabolic benefits, with a focus on Roux-en-Y gastric bypass (RYGB) and vertical sleeve gastrectomy (VSG), in both humans and rodents. MAJOR CONCLUSIONS Gut-brain communication and its brain targets of food intake control and energy balance regulation are complex and redundant. Although the relatively young science of bariatric surgery has generated a number of hypotheses, no clear and unique mechanism has yet emerged. It seems increasingly likely that the broad physiological and behavioral effects produced by bariatric surgery do not involve a single mechanism, but rather multiple signaling pathways. Besides a need to improve and better validate surgeries in animals, advanced techniques, including inducible, tissue-specific knockout models, and the use of humanized physiological traits will be necessary. State-of-the-art genetically-guided neural identification techniques should be used to more selectively manipulate function-specific pathways.
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Affiliation(s)
- Vance L Albaugh
- Translational and Integrative Gastrointestinal and Endocrine Research Laboratory, Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, LA, USA
| | - Yanlin He
- Brain Glycemic and Metabolism Control Department, Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, LA, USA
| | - Heike Münzberg
- Neurobiology of Nutrition & Metabolism Department, Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, LA, USA
| | - Christopher D Morrison
- Neurobiology of Nutrition & Metabolism Department, Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, LA, USA
| | - Sangho Yu
- Neurobiology of Nutrition & Metabolism Department, Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, LA, USA
| | - Hans-Rudolf Berthoud
- Neurobiology of Nutrition & Metabolism Department, Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, LA, USA.
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10
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Alamro N, Azhri AS, Almuqati A, Azzeh F, Azhar W, Qadhi A, Almohmadi NH, Abusudah WF, Ghafouri K. Effect of Bariatric Surgery on Metabolic Syndrome, Framingham Risk Scores and Thyroid Function during One-Year Follow-Up: A Saudi Retrospective Study. Healthcare (Basel) 2022; 10:healthcare10122530. [PMID: 36554054 PMCID: PMC9778226 DOI: 10.3390/healthcare10122530] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2022] [Revised: 12/11/2022] [Accepted: 12/12/2022] [Indexed: 12/16/2022] Open
Abstract
Bariatric surgery (BS) has been demonstrated to achieve sustained weight loss with significant metabolic improvement, including a reduction in cardiovascular disease and diabetes. The aim of this retrospective study is to measure the effect of BS on the Framingham risk score (FRS) and metabolic syndrome (MetS) among patients who underwent bariatric surgery. Additionally, we determine the effect of BS on thyroid-stimulating hormone (TSH) among euthyroid obese patients. A retrospective follow-up study was conducted at King Abdullah Medical City, Makkah, Saudi Arabia. A total of 160 patients underwent BS and completed one-year follow-up visits. Medical history, anthropometric, biochemical, and hormonal parameters were evaluated at baseline and 3−12 months after BS. The International Diabetes Federation (IDF) criteria were used to diagnose MetS. There was a significant decrease in systolic blood pressure (SBP), diastolic blood pressure (DBP), glycated hemoglobin (Hba1c), TSH, low-density lipoprotein (LDL), triglycerides, and total cholesterol (p < 0.001). A significant decrease was seen in MetS, BMI, FRS, SBP, DBP, Hba1c, LDL, triglycerides, cholesterol, and liver enzymes, with a significant increase in high-density lipoprotein levels 12 months postoperatively (p < 0.001). At 12 months, the prevalence of MetS, DM, and HTN and the FRS significantly decreased from 72.5%, 43.1%, 78.1%, and 11.4 to 16.3%, 9.4%, 22.5%, and 5.4, respectively. In addition to achieving substantial weight loss, BS improves MetS prevalence and cardiovascular risk profiles.
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Affiliation(s)
- Nuha Alamro
- Clinical Nutrition Administration, King Abdullah Medical City, P.O.Box 24246, Makkah 21955, Saudi Arabia
| | - Afnan S. Azhri
- Clinical Nutrition Administration, King Abdullah Medical City, P.O.Box 24246, Makkah 21955, Saudi Arabia
| | - Asma Almuqati
- Clinical Nutrition Administration, King Abdullah Medical City, P.O.Box 24246, Makkah 21955, Saudi Arabia
| | - Firas Azzeh
- Clinical Nutrition Department, Faculty of Applied Medical Sciences, Umm Al-Qura University, P.O Box 715, Makkah 21955, Saudi Arabia
| | - Wedad Azhar
- Clinical Nutrition Department, Faculty of Applied Medical Sciences, Umm Al-Qura University, P.O Box 715, Makkah 21955, Saudi Arabia
| | - Alaa Qadhi
- Clinical Nutrition Department, Faculty of Applied Medical Sciences, Umm Al-Qura University, P.O Box 715, Makkah 21955, Saudi Arabia
| | - Najlaa H. Almohmadi
- Clinical Nutrition Department, Faculty of Applied Medical Sciences, Umm Al-Qura University, P.O Box 715, Makkah 21955, Saudi Arabia
| | - Wafaa F. Abusudah
- Clinical Nutrition Department, Faculty of Applied Medical Sciences, Umm Al-Qura University, P.O Box 715, Makkah 21955, Saudi Arabia
| | - Khloud Ghafouri
- Clinical Nutrition Department, Faculty of Applied Medical Sciences, Umm Al-Qura University, P.O Box 715, Makkah 21955, Saudi Arabia
- Correspondence: ; Tel.: +966-125-270-000
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11
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Sridhar A, Khan D, Abdelaal M, Elliott JA, Naughton V, Flatt PR, Le Roux CW, Docherty NG, Moffett CR. Differential effects of RYGB surgery and best medical treatment for obesity-diabetes on intestinal and islet adaptations in obese-diabetic ZDSD rats. PLoS One 2022; 17:e0274788. [PMID: 36137097 PMCID: PMC9499270 DOI: 10.1371/journal.pone.0274788] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2022] [Accepted: 09/05/2022] [Indexed: 11/19/2022] Open
Abstract
Modification of gut-islet secretions after Roux-En-Y gastric bypass (RYBG) surgery contributes to its metabolic and anti-diabetic benefits. However, there is limited knowledge on tissue-specific hormone distribution post-RYGB surgery and how this compares with best medical treatment (BMT). In the present study, pancreatic and ileal tissues were excised from male Zucker-Diabetic Sprague Dawley (ZDSD) rats 8-weeks after RYGB, BMT (daily oral dosing with metformin 300mg/kg, fenofibrate 100mg/kg, ramipril 1mg/kg, rosuvastatin 10mg/kg and subcutaneous liraglutide 0.2mg/kg) or sham operation (laparotomy). Insulin, glucagon, somatostatin, PYY, GLP-1 and GIP expression patterns were assessed using immunocytochemistry and analyzed using ImageJ. After RYGB and BMT, body weight and plasma glucose were decreased. Intestinal morphometry was unaltered by RYGB, but crypt depth was decreased by BMT. Intestinal PYY cells were increased by both interventions. GLP-1- and GIP-cell counts were unchanged by RYGB but BMT increased ileal GLP-1-cells and decreased those expressing GIP. The intestinal contents of PYY and GLP-1 were significantly enhanced by RYGB, whereas BMT decreased ileal GLP-1. No changes of islet and beta-cell area or proliferation were observed, but the extent of beta-cell apoptosis and islet integrity calculated using circularity index were improved by both treatments. Significantly decreased islet alpha-cell areas were observed in both groups, while beta- and PYY-cell areas were unchanged. RYGB also induced a decrease in islet delta-cell area. PYY and GLP-1 colocalization with glucagon in islets was significantly decreased in both groups, while co-staining of PYY with glucagon was decreased and that with somatostatin increased. These data characterize significant cellular islet and intestinal adaptations following RYGB and BMT associated with amelioration of obesity-diabetes in ZDSD rats. The differential responses observed and particularly those within islets, may provide important clues to the unique ability of RYGB to cause diabetes remission.
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Affiliation(s)
- Ananyaa Sridhar
- Biomedical Sciences Research Institute, School of Biomedical Sciences, Ulster University, Coleraine, Northern Ireland, United Kingdom
| | - Dawood Khan
- Biomedical Sciences Research Institute, School of Biomedical Sciences, Ulster University, Coleraine, Northern Ireland, United Kingdom
- * E-mail:
| | - Mahmoud Abdelaal
- Diabetes Complications Research Centre, School of Medicine, Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Dublin, Ireland
| | - Jessie A. Elliott
- Department of Surgery, Trinity Centre for Health Sciences and St. James’s Hospital, Dublin, Ireland
| | - Violetta Naughton
- Biomedical Sciences Research Institute, School of Biomedical Sciences, Ulster University, Coleraine, Northern Ireland, United Kingdom
| | - Peter R. Flatt
- Biomedical Sciences Research Institute, School of Biomedical Sciences, Ulster University, Coleraine, Northern Ireland, United Kingdom
| | - Carel W. Le Roux
- Diabetes Complications Research Centre, School of Medicine, Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Dublin, Ireland
| | - Neil G. Docherty
- Diabetes Complications Research Centre, School of Medicine, Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Dublin, Ireland
| | - Charlotte R. Moffett
- Biomedical Sciences Research Institute, School of Biomedical Sciences, Ulster University, Coleraine, Northern Ireland, United Kingdom
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12
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Singhal V, Nimmala S, Karzar NH, Bredella M, Misra M. One-Year Self-Reported Appetite Is Similar in Adolescents with Obesity Who Do or Do Not Undergo Sleeve Gastrectomy. Nutrients 2022; 14:3054. [PMID: 35893908 PMCID: PMC9331365 DOI: 10.3390/nu14153054] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2022] [Revised: 07/11/2022] [Accepted: 07/21/2022] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND With the growing prevalence of severe obesity in adolescents, sleeve gastrectomy (SG), a type of metabolic bariatric surgery (MBS), is increasingly being performed at a younger age. Data regarding changes in homeostatic and hedonic appetite following SG are conflicting in adults, with some studies showing no change and others showing a decrease in appetite. Data evaluating the effect of SG on appetite during adolescence, when appetite is more plastic, are currently lacking. OBJECTIVE To evaluate appetite changes one year after SG in adolescents with obesity vs. in non-surgical controls (NS). METHODS Thirty-nine subjects 13-21 years old with severe obesity were followed for a year; 19 underwent SG, and 20 were followed without surgery. Subjects had fasting blood tests for appetite-regulating hormones and completed a visual analog scale for appetite assessment (VAS). RESULTS The SG group had a decrease in body mass index (BMI) at one-year (baseline: 48.2 ± 1.7 kg/m2; one-year follow-up: 42.6 ± 1.0 kg/m2 (p ≤ 0.0001)). No within- or between-group differences were noted in the one-year change in appetite in the SG and NS groups. After SG, fasting ghrelin decreased (p ≤ 0.0001); however, no changes were noted in peptide YY (PYY) levels. Changes in one homeostatic appetite measure following SG were inversely associated with changes in fasting PYY (r = -0.583, p = 0.011). Appetite changes were not associated with weight loss or final BMI. CONCLUSIONS There were no changes in appetite measures one-year after SG from pre-surgery levels in adolescents with obesity, and appetite changes were not associated with changes in BMI. It is important to evaluate the impact of long-term appetite changes, if any, on weight loss after SG.
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Affiliation(s)
- Vibha Singhal
- Neuroendocrine Unit, Massachusetts General Hospital, Harvard Medical School, 55 Fruit st, Boston, MA 02114, USA; (S.N.); (N.H.K.); (M.M.)
- Division of Pediatric Endocrinology, Massachusetts General Hospital, Harvard Medical School, 55 Fruit st, Boston, MA 02114, USA
- MGH Weight Center, Massachusetts General Hospital, Harvard Medical School, 55 Fruit st, Boston, MA 02114, USA
| | - Supritha Nimmala
- Neuroendocrine Unit, Massachusetts General Hospital, Harvard Medical School, 55 Fruit st, Boston, MA 02114, USA; (S.N.); (N.H.K.); (M.M.)
| | - Nazanin Hazhir Karzar
- Neuroendocrine Unit, Massachusetts General Hospital, Harvard Medical School, 55 Fruit st, Boston, MA 02114, USA; (S.N.); (N.H.K.); (M.M.)
| | - Miriam Bredella
- Department of Radiology, Massachusetts General Hospital, Harvard Medical School, 55 Fruit st, Boston, MA 02114, USA;
| | - Madhusmita Misra
- Neuroendocrine Unit, Massachusetts General Hospital, Harvard Medical School, 55 Fruit st, Boston, MA 02114, USA; (S.N.); (N.H.K.); (M.M.)
- Division of Pediatric Endocrinology, Massachusetts General Hospital, Harvard Medical School, 55 Fruit st, Boston, MA 02114, USA
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13
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Nymo S, Børresen Skjølsvold O, Aukan M, Finlayson G, Græslie H, Mårvik R, Kulseng B, Sandvik J, Martins C. Suboptimal Weight Loss 13 Years After Roux-en-Y Gastric Bypass: Is Hedonic Hunger, Eating Behaviour and Food Reward to Blame? Obes Surg 2022; 32:2263-2271. [PMID: 35505168 PMCID: PMC9276719 DOI: 10.1007/s11695-022-06075-z] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2021] [Revised: 04/16/2022] [Accepted: 04/20/2022] [Indexed: 11/28/2022]
Abstract
Purpose Suboptimal weight loss (SWL) and weight regain (WR) following bariatric surgery are common. The exact reasons for this phenomenon remain to be fully elucidated. To compare hedonic hunger, food preferences, food reward and eating behaviour traits between participants with SWL and optimal weight loss (OWL) 13 years after Roux-en-Y gastric bypass (RYGB). Materials and Method Cross-sectional case control study where participants experiencing SWL or OWL (< or ≥ 50% of excess weight, respectively) post-RYGB were compared to a non-surgical control group matched for pre-operative body mass index. Hedonic hunger (Power of Food Scale), implicit and explicit liking and wanting for high-fat and low-fat savoury and sweet food (Leeds Food Preference Questionnaire) and eating behaviour (Dutch Eating Behavior Questionnaire, Three-Factor Eating Questionnaire and the Food Cravings Questionnaires State and Trait-reduced) were assessed. Results In total, 75 participants were recruited from the bariatric surgery observation study (BAROBS). Disinhibition, hunger, emotional, external and restrained eating, frequency of cravings and hedonic hunger were lower in the OWL, compared with the SWL and/or control groups. Implicit wanting and explicit liking and wanting for high-fat savoury and high-fat sweet food were lower, and implicit wanting for low-fat savoury food higher, in the OWL, compared with the SWL and/or control groups. Conclusion SWL 13 years after RYGB is associated with dysfunctional eating behaviours, increased preference and reward for high-fat food and increased hedonic hunger. Future longitudinal studies are needed to establish the cause-effect relationship between these variables. Graphical abstract ![]()
Supplementary Information The online version contains supplementary material available at 10.1007/s11695-022-06075-z.
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Affiliation(s)
- Siren Nymo
- Obesity Research Group, Department of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology (NTNU), Prinsesse Kristinas gate 5, 7030, Forsyningssenteret, Trondheim, Norway. .,Centre for Obesity and Innovation (ObeCe), Clinic of Surgery, St. Olav University Hospital, Trondheim, Norway. .,Clinic of Surgery, Namsos Hospital, Nord-Trøndelag Hospital Trust, Namsos, Norway. .,Department of Nutrition Sciences, University of Alabama at Birmingham, Birmingham, AL, USA.
| | - Oda Børresen Skjølsvold
- Obesity Research Group, Department of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology (NTNU), Prinsesse Kristinas gate 5, 7030, Forsyningssenteret, Trondheim, Norway.,Department of Nutrition Sciences, University of Alabama at Birmingham, Birmingham, AL, USA
| | - Marthe Aukan
- Obesity Research Group, Department of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology (NTNU), Prinsesse Kristinas gate 5, 7030, Forsyningssenteret, Trondheim, Norway.,Centre for Obesity and Innovation (ObeCe), Clinic of Surgery, St. Olav University Hospital, Trondheim, Norway.,Department of Nutrition Sciences, University of Alabama at Birmingham, Birmingham, AL, USA
| | - Graham Finlayson
- School of Psychology, University of Leeds, Leeds, UK.,Department of Nutrition Sciences, University of Alabama at Birmingham, Birmingham, AL, USA
| | - Hallvard Græslie
- Clinic of Surgery, Namsos Hospital, Nord-Trøndelag Hospital Trust, Namsos, Norway.,Department of Nutrition Sciences, University of Alabama at Birmingham, Birmingham, AL, USA
| | - Ronald Mårvik
- Obesity Research Group, Department of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology (NTNU), Prinsesse Kristinas gate 5, 7030, Forsyningssenteret, Trondheim, Norway.,Centre for Obesity and Innovation (ObeCe), Clinic of Surgery, St. Olav University Hospital, Trondheim, Norway.,Department of Nutrition Sciences, University of Alabama at Birmingham, Birmingham, AL, USA
| | - Bård Kulseng
- Obesity Research Group, Department of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology (NTNU), Prinsesse Kristinas gate 5, 7030, Forsyningssenteret, Trondheim, Norway.,Centre for Obesity and Innovation (ObeCe), Clinic of Surgery, St. Olav University Hospital, Trondheim, Norway.,Department of Nutrition Sciences, University of Alabama at Birmingham, Birmingham, AL, USA
| | - Jorunn Sandvik
- Obesity Research Group, Department of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology (NTNU), Prinsesse Kristinas gate 5, 7030, Forsyningssenteret, Trondheim, Norway.,Centre for Obesity and Innovation (ObeCe), Clinic of Surgery, St. Olav University Hospital, Trondheim, Norway.,Clinic of Surgery, Ålesund Hospital, Møre- og Romsdal Hospital Trust, Ålesund, Norway.,Department of Nutrition Sciences, University of Alabama at Birmingham, Birmingham, AL, USA
| | - Catia Martins
- Obesity Research Group, Department of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology (NTNU), Prinsesse Kristinas gate 5, 7030, Forsyningssenteret, Trondheim, Norway.,Centre for Obesity and Innovation (ObeCe), Clinic of Surgery, St. Olav University Hospital, Trondheim, Norway.,Department of Nutrition Sciences, University of Alabama at Birmingham, Birmingham, AL, USA
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14
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Rebello CJ, Greenway FL, Zhang D, Johnson WD, Patterson E, Raum W. Sympathomimetic increases resting energy expenditure following bariatric surgery: A randomized controlled clinical trial. Obesity (Silver Spring) 2022; 30:874-883. [PMID: 35244344 PMCID: PMC10167942 DOI: 10.1002/oby.23384] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/20/2021] [Revised: 12/29/2021] [Accepted: 01/06/2022] [Indexed: 11/08/2022]
Abstract
OBJECTIVE The aim of this study was to test the hypothesis that ephedrine + caffeine (EC) reduces the fall in resting energy expenditure (REE) following bariatric surgery. METHODS This 32-week, randomized, double-blinded, placebo-controlled trial included 142 patients who underwent Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy (SG) surgery. Participants were randomized to either EC or placebo for 27 weeks, beginning 5 weeks post surgery. The primary end points were change in REE (measured), percentage of predicted REE ([measured REE/Harris-Benedict equation-predicted REE] × 100), and body composition. Secondary outcomes included change in percentage of weight. Adverse events (AEs) were recorded. RESULTS The reduction in REE was smaller in the EC versus the placebo group, but it was not significant. Percentage of predicted REE was increased in the EC versus the placebo group (difference, mean [SE]: 5.82 [2.29], p = 0.013). Percentage of weight (difference: -3.83 [1.39], p = 0.007) was reduced in the EC versus the placebo group. Percentage of predicted REE was increased and body weight decreased in the EC-treated participants who underwent SG compared with those who underwent SG and were treated with placebo (difference in percentage of predicted REE = 8.06 [2.83], p = 0.006; difference in weight percentage = -4.37 [1.92], p = 0.025). Percentage of fat-free mass was increased in the SG participants treated with EC versus placebo (difference: 1.31 [0.63], p = 0.042). The most common AEs were anxiety, dizziness, insomnia, and tremors. Most AEs were not different from placebo by Week 32. CONCLUSIONS EC enhances weight loss and reduces the fall in REE following bariatric surgery. Adrenergic symptoms mostly resolve over time.
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Affiliation(s)
- Candida J. Rebello
- Pennington Biomedical Research Center, Louisiana State University System, 6400 Perkins Road, Baton Rouge, LA 70808, USA
| | - Frank L. Greenway
- Pennington Biomedical Research Center, Louisiana State University System, 6400 Perkins Road, Baton Rouge, LA 70808, USA
| | - Dachuan Zhang
- Pennington Biomedical Research Center, Louisiana State University System, 6400 Perkins Road, Baton Rouge, LA 70808, USA
| | - William D. Johnson
- Pennington Biomedical Research Center, Louisiana State University System, 6400 Perkins Road, Baton Rouge, LA 70808, USA
| | | | - William Raum
- Oregon Weight Loss Surgery, LLC Portland, Oregon, USA
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15
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Akalestou E, Miras AD, Rutter GA, le Roux CW. Mechanisms of Weight Loss After Obesity Surgery. Endocr Rev 2022; 43:19-34. [PMID: 34363458 PMCID: PMC8755990 DOI: 10.1210/endrev/bnab022] [Citation(s) in RCA: 70] [Impact Index Per Article: 23.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/15/2021] [Indexed: 02/07/2023]
Abstract
Obesity surgery remains the most effective treatment for obesity and its complications. Weight loss was initially attributed to decreased energy absorption from the gut but has since been linked to reduced appetitive behavior and potentially increased energy expenditure. Implicated mechanisms associating rearrangement of the gastrointestinal tract with these metabolic outcomes include central appetite control, release of gut peptides, change in microbiota, and bile acids. However, the exact combination and timing of signals remain largely unknown. In this review, we survey recent research investigating these mechanisms, and seek to provide insights on unanswered questions over how weight loss is achieved following bariatric surgery which may eventually lead to safer, nonsurgical weight-loss interventions or combinations of medications with surgery.
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Affiliation(s)
- Elina Akalestou
- Section of Cell Biology and Functional Genomics, Division of Diabetes, Endocrinology and Metabolism, Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK
| | - Alexander D Miras
- Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK
| | - Guy A Rutter
- Section of Cell Biology and Functional Genomics, Division of Diabetes, Endocrinology and Metabolism, Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK.,Lee Kong Chian Imperial Medical School, Nanyang Technological University, Singapore.,University of Montreal Hospital Research Centre, Montreal, QC, Canada
| | - Carel W le Roux
- Diabetes Complications Research Centre, University College Dublin, Ireland.,Diabetes Research Group, School of Biomedical Science, Ulster University, Belfast, UK
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16
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Mirhosseini Dehabadi S, Sayadi Shahraki M, Mahmoudieh M, Kalidari B, Melali H, Mousavi M, Ghourban Abadi M, Mirhosseini S. Bone health after bariatric surgery: Consequences, prevention, and treatment. Adv Biomed Res 2022; 11:92. [DOI: 10.4103/abr.abr_182_21] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2021] [Revised: 07/15/2021] [Accepted: 07/20/2021] [Indexed: 11/05/2022] Open
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17
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Gao X, Dai S, Wang G, Li W, Song Z, Su Z, Zhu S, Zhu L, Li P. Large Versus Small Gastric Pouch for Roux-en-Y Gastric Bypass in Individuals With Type 2 Diabetes and a Body Mass Index < 35 kg/m2: Six-Year Outcomes. Front Endocrinol (Lausanne) 2022; 13:913062. [PMID: 36120423 PMCID: PMC9474650 DOI: 10.3389/fendo.2022.913062] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/05/2022] [Accepted: 06/22/2022] [Indexed: 11/24/2022] Open
Abstract
BACKGROUND Roux-en-Y gastric bypass (RYGB) results in extraordinary weight loss and glycemic control outcomes for patients with obesity; however, the effect of gastric pouch size is still unclear, and the reported results are contradictory. Additionally, long-term data on type 2 diabetes (T2D) patients with low body mass index (BMI) are sparse. This study was to assess the effect of 6-year outcomes in Chinese patients with T2D and a BMI < 35 kg/m2 who underwent RYGB with gastric pouches of different sizes. METHODS A retrospective cohort study was performed. There were 42 patients in the large gastric pouch group (L) and 53 patients in the small gastric pouch group (S). Baseline demographic history, pre- and postoperative BMI, waist circumference, and glucose- and lipid metabolism-related indicators were compared. RESULTS Assessments were completed in 100%, 100%, 93.6%, and 89.4% of patients at baseline, 1 year, 3 years, and 6 years, respectively. At 6 years, the changes in BMI and fasting plasma glucose were greater in the S group (-4.25 ± 0.51 kg/m2 and -4.58 ± 0.73 mmol/l) than in the L group (-2.06 ± 0.48 kg/m2 and -2.64 ± 0.61 mmol/l). The independent predictors of complete remission of T2D were preoperative BMI and the size of the gastric pouch. A large gastric pouch was associated with a higher risk for marginal ulcers. CONCLUSIONS A small gastric pouch results in better weight loss and glycemic control. High preoperative BMI and a small gastric pouch are associated with better T2D remission rates. A large gastric pouch leads to a higher incidence of marginal ulcers.
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Affiliation(s)
| | | | | | | | | | | | | | - Liyong Zhu
- *Correspondence: Pengzhou Li, ; Liyong Zhu, @uni.edu
| | - Pengzhou Li
- *Correspondence: Pengzhou Li, ; Liyong Zhu, @uni.edu
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18
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Redpath TL, Livingstone MBE, Dunne AA, Boyd A, le Roux CW, Spector AC, Price RK. Methodological issues in assessing change in dietary intake and appetite following gastric bypass surgery: A systematic review. Obes Rev 2021; 22:e13202. [PMID: 33527664 PMCID: PMC8244068 DOI: 10.1111/obr.13202] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/12/2020] [Revised: 11/20/2020] [Accepted: 12/13/2020] [Indexed: 12/23/2022]
Abstract
Gastric bypass surgery is an effective long-term treatment for individuals with severe obesity. Changes in appetite, dietary intake, and food preferences have all been postulated to contribute to postoperative body weight regulation, however, findings are inconsistent. The aim of this systematic review was to evaluate the current literature on changes in dietary intake and appetite following gastric bypass surgery, in the context of the methodology used and the analysis, interpretation, and presentation of results. Four databases were systematically searched with terms related to "gastric bypass surgery," "appetite," and "dietary intake," and 49 papers (n = 2384 patients after gastric bypass) were eligible for inclusion. The evidence indicated that only a reduction in overall energy intake and an increase in postprandial satiety are maintained beyond 6-month post-surgery, whereas relative macronutrient intake and premeal hunger remain unchanged. However, available data were limited by inconsistencies in the methods, analysis, presentation, and interpretation of results. In particular, there was a reliance on data collected by subjective methods with minimal acknowledgment of the limitations, such as misreporting of food intake. There is a need for further work employing objective measurement of appetite and dietary intake following gastric bypass surgery to determine how these mechanisms may contribute to weight regulation in the longer term.
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Affiliation(s)
- Tamsyn L Redpath
- Nutrition Innovation Centre for Food and Health, Ulster University, Coleraine, UK
| | | | - Aoibheann A Dunne
- Nutrition Innovation Centre for Food and Health, Ulster University, Coleraine, UK
| | - Adele Boyd
- Nutrition Innovation Centre for Food and Health, Ulster University, Coleraine, UK
| | - Carel W le Roux
- Diabetes Complications Research Centre, University College Dublin, Dublin, Ireland
| | - Alan C Spector
- Department of Psychology and Program in Neuroscience, Florida State University, Tallahassee, Florida, USA
| | - Ruth K Price
- Nutrition Innovation Centre for Food and Health, Ulster University, Coleraine, UK
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19
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Nielsen MS, Søberg S, Schmidt JB, Chenchar A, Sjödin A, Gillum MP. Transient postprandial increase in intact circulating fibroblast growth factor-21 levels after Roux-en-Y gastric bypass: a randomized controlled clinical trial. PeerJ 2021; 9:e11174. [PMID: 33954037 PMCID: PMC8052976 DOI: 10.7717/peerj.11174] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2020] [Accepted: 03/08/2021] [Indexed: 01/05/2023] Open
Abstract
Background Despite a consistent link between obesity and increased circulating levels of fibroblast growth factor-21 (FGF21), the effect of weight-loss interventions on FGF21 is not clear. We aimed to determine the short- and long-term effects of Roux-en-Y gastric bypass (RYGB) on intact plasma FGF21 levels and to test the hypothesis that RYGB, but not diet-induced weight loss, increases fasting and postprandial responses of FGF21. Method Twenty-eight participants with obesity followed a low-calorie diet for 11 weeks. The 28 participants were randomized to undergo RYGB surgery at week 8 (RYGB group, n = 14), or to a control group scheduled for surgery at week 12 (n = 14). Fasting levels of intact, biologically active FGF21 (amino acids 1-181) and its postprandial responses to a mixed meal were assessed at week 7 and 11, and 78 weeks (18 months) after RYGB. Results At week 11 (3 weeks after RYGB), postprandial responses of intact FGF21 were enhanced in participants undergoing surgery at week 8 (change from week 7 to 11: P = 0.02), whereas no change was found in non-operated control participants in similar negative energy balance (change from week 7 to 11: P = 0.81). However, no between-group difference was found (P = 0.27 for the group-week-time interaction). Fasting, as well as postprandial responses in intact FGF21, were unchanged 18 months after RYGB when both the RYGB and control group were collapsed together (change from week 7 to 78 weeks after RYGB: P = 0.17). Conclusion Postprandial intact FGF21 levels were enhanced acutely after RYGB whereas no signs of sustained changes were found 18 months after surgery. When comparing the acute effect of RYGB with controls in similar negative energy balance, we failed to detect any significant differences between groups, probably due to the small sample size and large inter-individual variations, especially in response to surgery.
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Affiliation(s)
- Mette S Nielsen
- Department of Nutrition, Exercise and Sports, Faculty of Science, University of Copenhagen, Frederiksberg, Denmark.,Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Susanna Søberg
- Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.,The Center of Inflammation and Metabolism and the Center for Physical Activity Research, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
| | - Julie B Schmidt
- Department of Nutrition, Exercise and Sports, Faculty of Science, University of Copenhagen, Frederiksberg, Denmark
| | - Anne Chenchar
- Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Anders Sjödin
- Department of Nutrition, Exercise and Sports, Faculty of Science, University of Copenhagen, Frederiksberg, Denmark
| | - Matthew P Gillum
- Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
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20
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Camacho-Ramírez A, Prada-Oliveira JA, Ribelles-García A, Almorza-Gomar D, Pérez-Arana GM. The Leading Role of Peptide Tyrosine Tyrosine in Glycemic Control After Roux-en-Y Gastric Bypass in Rats. Obes Surg 2021; 30:697-706. [PMID: 31701411 DOI: 10.1007/s11695-019-04239-y] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
AIMS Roux-en-Y gastric bypass (RYGB) is one of the most effective surgical therapies for the rapid resolution of type 2 diabetes. However, the mechanisms underlying the entero-hormonal response after surgery and the role of peptide tyrosine tyrosine (PYY) in the restoration of normoglycemia are still not clear. METHODS We reproduced the RYGB technique in Wistar and Goto-Kakizaki rats and performed serum hormonal, histological, and hormonal-infusion test. RESULTS Using the diabetic Goto-Kakizaki (GK) rat model, we demonstrated that PYY plasma levels showed a remarkable peak approximately 30 min earlier than GLP-1 or GIP after mixed-meal administration in RYGB-operated rats with PYY. The GLP-1 and GIP areas under the curve (AUCs) increased after RYGB in GK rats. Additionally, the findings suggested that PYY (3-36) infusion led to increased GLP-1 and GIP plasma levels close to those obtained after a meal. Finally, the number of GLP-1-positive cells appeared to increase in the three segments of the small intestine in GK-RYGB-operated rats beyond the early presence of nutrient stimulation in the ileum. Nevertheless, PYY-positive cell numbers appeared to increase only in the ileum. CONCLUSION At least in rats, these data demonstrate an earlier essential role for PYY in gut hormone regulation after RYGB. We understand that PYY contributes to GLP-1 and GIP release and there must be the existence of enteroendocrine communication routes between the distal and proximal small intestine.
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Affiliation(s)
- Alonso Camacho-Ramírez
- Puerta del Mar Hospital, University of Cadiz, Cadiz, Spain.,Asociación Gaditana de Apoyo al Investigador, Cadiz, Spain.,Biomedical Science Research and Innovation Institute (INIBICA), University of Cadiz, Cadiz, Spain
| | - J Arturo Prada-Oliveira
- Asociación Gaditana de Apoyo al Investigador, Cadiz, Spain.,Biomedical Science Research and Innovation Institute (INIBICA), University of Cadiz, Cadiz, Spain.,Department of Human Anatomy and Embryology, Faculty of Medicine, University of Cadiz, Plaza Fragela s/n, 11003, Cadiz, Spain
| | - Antonio Ribelles-García
- Department of Human Anatomy and Embryology, Faculty of Medicine, University of Cadiz, Plaza Fragela s/n, 11003, Cadiz, Spain.,Sustainable Social Development Research Institute (INDESS), University of Cadiz, Cadiz, Spain
| | - David Almorza-Gomar
- Biomedical Science Research and Innovation Institute (INIBICA), University of Cadiz, Cadiz, Spain.,Operative Statistic and Research Department, University of Cadiz, Cadiz, Spain
| | - Gonzalo M Pérez-Arana
- Asociación Gaditana de Apoyo al Investigador, Cadiz, Spain. .,Biomedical Science Research and Innovation Institute (INIBICA), University of Cadiz, Cadiz, Spain. .,Department of Human Anatomy and Embryology, Faculty of Medicine, University of Cadiz, Plaza Fragela s/n, 11003, Cadiz, Spain.
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21
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Abdalla M, Jones DB. Weight Loss Following Roux-en-Y Gastric Bypass Causally Implicated with Serum Levels of IL-22: A Mendelian Randomization and Phenome-Wide Association Study. Obesity (Silver Spring) 2021; 29:610-615. [PMID: 33528908 DOI: 10.1002/oby.23097] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/28/2020] [Revised: 11/11/2020] [Accepted: 11/16/2020] [Indexed: 11/06/2022]
Abstract
OBJECTIVE Laparoscopic Roux-en-Y gastric bypass (RYGB) modulates the low-grade inflammatory state associated with severe obesity. This study sought to investigate whether weight loss is causally implicated with changes in serum levels of inflammatory molecules. METHODS Using the largest genome-wide association study (n = 1,020 individuals), this study curated five genetic variants associated with weight loss following RYGB. Phenome-wide association studies (PheWAS) were performed to identify other phenotypes associated with these variants. Subsequently, two-sample Mendelian randomization was used to study the causal effects of weight loss on the serum levels of 382 inflammatory proteins (measured in 3,033 individuals). This is the first systematic quasi-experimental investigation of weight loss following RYGB and serum markers of inflammation. RESULTS The PheWAS analysis revealed that four of the five variants are associated with phenotypes relating to metabolism and inflammation, including insulin response and levels of C-reactive protein. Two-sample Mendelian randomization of the 382 serum inflammatory markers revealed that weight loss following RYGB increases serum levels of interleukin 22 (IL-22) (beta = 0.021, P < 10-3 ; 95% CI: 0.010-0.031). Sensitivity analyses further supported the results and the causal direction. CONCLUSIONS Weight loss following RYGB may cause an increase in IL-22 serum levels, suggesting that weight loss directly contributes to immune modulation following bypass. These results demonstrate the utility of genetic studies to disentangling molecular cause and effect following bariatric surgery.
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Affiliation(s)
- Moustafa Abdalla
- Harvard Medical School, Harvard University, Boston, Massachusetts, USA
- Computational Statistics and Machine Learning Group, Department of Statistics, University of Oxford, Oxford, UK
- Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK
| | - Daniel B Jones
- Harvard Medical School, Harvard University, Boston, Massachusetts, USA
- Department of Surgery, Division of Minimally Invasive Surgery & Bariatric Surgery, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA
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22
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Hagemann CA, Zhang C, Hansen HH, Jorsal T, Rigbolt KTG, Madsen MR, Bergmann NC, Heimbürger SMN, Falkenhahn M, Theis S, Breitschopf K, Holm S, Hedegaard MA, Christensen MB, Vilsbøll T, Holst B, Vrang N, Jelsing J, Knop FK. Identification and Metabolic Profiling of a Novel Human Gut-derived LEAP2 Fragment. J Clin Endocrinol Metab 2021; 106:e966-e981. [PMID: 33135737 DOI: 10.1210/clinem/dgaa803] [Citation(s) in RCA: 29] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/12/2020] [Indexed: 02/06/2023]
Abstract
CONTEXT The mechanisms underlying Roux-en-Y gastric bypass (RYGB) surgery-induced weight loss and the immediate postoperative beneficial metabolic effects associated with the operation remain uncertain. Enteroendocrine cell (EEC) secretory function has been proposed as a key factor in the marked metabolic benefits from RYGB surgery. OBJECTIVE To identify novel gut-derived peptides with therapeutic potential in obesity and/or diabetes by profiling EEC-specific molecular changes in obese patients following RYGB-induced weight loss. SUBJECTS AND METHODS Genome-wide expression analysis was performed in isolated human small intestinal EECs obtained from 20 gut-biopsied obese subjects before and after RYGB. Targets of interest were profiled for preclinical and clinical metabolic effects. RESULTS Roux-en-Y gastric bypass consistently increased expression levels of the inverse ghrelin receptor agonist, liver-expressed antimicrobial peptide 2 (LEAP2). A secreted endogenous LEAP2 fragment (LEAP238-47) demonstrated robust insulinotropic properties, stimulating insulin release in human pancreatic islets comparable to the gut hormone glucagon-like peptide-1. LEAP238-47 showed reciprocal effects on growth hormone secretagogue receptor (GHSR) activity, suggesting that the insulinotropic action of the peptide may be directly linked to attenuation of tonic GHSR activity. The fragment was infused in healthy human individuals (n = 10), but no glucoregulatory effect was observed in the chosen dose as compared to placebo. CONCLUSIONS Small intestinal LEAP2 expression was upregulated after RYGB. The corresponding circulating LEAP238-47 fragment demonstrated strong insulinotropic action in vitro but failed to elicit glucoregulatory effects in healthy human subjects.
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Affiliation(s)
- Christoffer A Hagemann
- Gubra Aps, Hørsholm, Denmark
- Center for Clinical Metabolic Research, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark
| | | | | | - Tina Jorsal
- Center for Clinical Metabolic Research, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark
| | | | | | - Natasha C Bergmann
- Center for Clinical Metabolic Research, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark
| | - Sebastian M N Heimbürger
- Center for Clinical Metabolic Research, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark
- Steno Diabetes Center Copenhagen, Gentofte, Denmark
| | | | | | | | - Stephanie Holm
- Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Morten A Hedegaard
- Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Mikkel B Christensen
- Center for Clinical Metabolic Research, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark
- Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
- Department of Clinical Pharmacology, Bispebjerg Hospital, University of Copenhagen, Copenhagen, Denmark
| | - Tina Vilsbøll
- Center for Clinical Metabolic Research, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark
- Steno Diabetes Center Copenhagen, Gentofte, Denmark
- Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Birgitte Holst
- Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark
- Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | | | | | - Filip K Knop
- Center for Clinical Metabolic Research, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark
- Steno Diabetes Center Copenhagen, Gentofte, Denmark
- Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
- Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
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23
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Cholecystectomy increases the risk of dumping syndrome and postbariatric hypoglycemia after bariatric surgery. Surg Obes Relat Dis 2020; 16:1939-1947. [PMID: 32980223 DOI: 10.1016/j.soard.2020.08.009] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2020] [Revised: 06/24/2020] [Accepted: 08/07/2020] [Indexed: 01/19/2023]
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24
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Alizadeh S. Letter to the editor on "Targeting bile acid metabolism in obesity reduction: A systematic review and meta-analysis". Obes Rev 2020; 21:e13071. [PMID: 32596963 DOI: 10.1111/obr.13071] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/05/2020] [Accepted: 05/15/2020] [Indexed: 11/29/2022]
Affiliation(s)
- Shahab Alizadeh
- Department of Clinical Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran, Iran
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25
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Baggio LL, Drucker DJ. Glucagon-like peptide-1 receptor co-agonists for treating metabolic disease. Mol Metab 2020; 46:101090. [PMID: 32987188 PMCID: PMC8085566 DOI: 10.1016/j.molmet.2020.101090] [Citation(s) in RCA: 173] [Impact Index Per Article: 34.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/28/2020] [Revised: 09/13/2020] [Accepted: 09/17/2020] [Indexed: 12/21/2022] Open
Abstract
Background Glucagon-like peptide-1 receptor (GLP-1R) agonists are approved to treat type 2 diabetes and obesity. They elicit robust improvements in glycemic control and weight loss, combined with cardioprotection in individuals at risk of or with pre-existing cardiovascular disease. These attributes make GLP-1 a preferred partner for next-generation therapies exhibiting improved efficacy yet retaining safety to treat diabetes, obesity, non-alcoholic steatohepatitis, and related cardiometabolic disorders. The available clinical data demonstrate that the best GLP-1R agonists are not yet competitive with bariatric surgery, emphasizing the need to further improve the efficacy of current medical therapy. Scope of review In this article, we discuss data highlighting the physiological and pharmacological attributes of potential peptide and non-peptide partners, exemplified by amylin, glucose-dependent insulinotropic polypeptide (GIP), and steroid hormones. We review the progress, limitations, and future considerations for translating findings from preclinical experiments to competitive efficacy and safety in humans with type 2 diabetes and obesity. Major conclusions Multiple co-agonist combinations exhibit promising clinical efficacy, notably tirzepatide and investigational amylin combinations. Simultaneously, increasing doses of GLP-1R agonists such as semaglutide produces substantial weight loss, raising the bar for the development of new unimolecular co-agonists. Collectively, the available data suggest that new co-agonists with robust efficacy should prove superior to GLP-1R agonists alone to treat metabolic disorders.
GLP-1 is a preferred partner for co-agonist development. Co-agonist combinations must exhibit improved weight loss beyond GLP-1 alone. Unimolecular coagonists must exhibit retained or improved cardioprotection. Obesity represents an optimal condition for the development of new GLP-1 co-agonists.
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Affiliation(s)
- Laurie L Baggio
- Lunenfeld-Tanenbaum Research Institute, Department of Medicine, Mt. Sinai Hospital, Toronto, Ontario, M5G 1X5 Canada
| | - Daniel J Drucker
- Lunenfeld-Tanenbaum Research Institute, Department of Medicine, Mt. Sinai Hospital, Toronto, Ontario, M5G 1X5 Canada.
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26
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Yang H, Liu H, Jiao Y, Qian J. Roux-en-Y Gastrointestinal Bypass Promotes Activation of TGR5 and Peptide YY. Endocr Metab Immune Disord Drug Targets 2020; 20:1262-1267. [PMID: 32600238 DOI: 10.2174/1871530320666200628024500] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/29/2019] [Revised: 04/26/2020] [Accepted: 05/04/2020] [Indexed: 12/18/2022]
Abstract
BACKGROUND G protein-coupled bile acid receptor (TGR5) is involved in a number of metabolic diseases. The aim of this study was to identify the role of TGR5 after Roux-en-Y gastric bypass (GBP). METHODS Wild type and TGR5 knockout mice (tgr5-/-) were fed a high-fat diet (HFD) to establish the obesity model. GBP was performed. The changes in body weight and food intake were measured. The levels of TGR5 and peptide YY (PYY) were evaluated by RT-PCR, Western blot, and ELISA. Moreover, the L-cells were separated from wild type and tgr5-/- mice. The levels of PYY in L-cells were evaluated by ELISA. RESULTS The body weights were significantly decreased after GBP in wild type mice (p<0.05), but not tgr5-/- mice (p>0.05). Food intake was reduced after GBP in wild type mice, but also not significantly affected in tgr5-/- mice (p>0.05). The levels of PYY were significantly increased after GBP compared with the sham group (p<0.05); however, in tgr5-/- mice the expression of PYY was not significantly affected (p>0.05). After INT-777 stimulation in L-cells obtained from murine intestines, the levels of PYY were significantly increased in L-cells tgr5+/+ (p<0.05). CONCLUSION Our study suggests that GBP up-regulated the expression of TGR5 in murine intestines, and increased the levels of PYY, which further reduced food intake and decreased the body weight.
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Affiliation(s)
- Haojun Yang
- Department of Gastrointestinal Surgery, Nanjing Medical University Affiliated Changzhou No. 2 People's Hospital, Changzhou, 213000, China
| | - Hanyang Liu
- Department of Gastrointestinal Surgery, Nanjing Medical University Affiliated Changzhou No. 2 People's Hospital, Changzhou, 213000, China
| | - YuWen Jiao
- Department of Gastrointestinal Surgery, Nanjing Medical University Affiliated Changzhou No. 2 People's Hospital, Changzhou, 213000, China
| | - Jun Qian
- Department of Gastrointestinal Surgery, Nanjing Medical University Affiliated Changzhou No. 2 People's Hospital, Changzhou, 213000, China
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27
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Ongoing Inconsistencies in Weight Loss Reporting Following Bariatric Surgery: a Systematic Review. Obes Surg 2020; 29:1375-1387. [PMID: 30671713 DOI: 10.1007/s11695-018-03702-6] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2023]
Abstract
Weight loss is the primary outcome following bariatric surgery; however, its documentation within current literature is heterogeneous and poorly defined, limiting meaningful comparison between studies. Randomized controlled trials from 2012 to 2016 were identified using the Medline database through "Gastric bypass OR sleeve gastrectomy AND weight" search terms. A total of 73 studies with 5948 patients were included. Reporting of preoperative weight was done primarily using mean body mass index (BMI) (87.7%) and mean weight (65.8%). Postoperative weight reporting was more variable, with the most frequently reported measure being mean postoperative BMI (71.2%). Overall, nearly one third of all bariatric literature contained discrepancies that precluded meaningful meta-analysis. Reporting of weight loss following bariatric surgery is becoming increasingly diverse for both pre- and post-operative outcomes. Ongoing heterogeneity will continue to act as a barrier to meaningful comparison of bariatric outcomes until standardized reporting practices become adopted.
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28
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Grandl G, Novikoff A, DiMarchi R, Tschöp MH, Müller TD. Gut Peptide Agonism in the Treatment of Obesity and Diabetes. Compr Physiol 2019; 10:99-124. [PMID: 31853954 DOI: 10.1002/cphy.c180044] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Obesity is a global healthcare challenge that gives rise to devastating diseases such as the metabolic syndrome, type-2 diabetes (T2D), and a variety of cardiovascular diseases. The escalating prevalence of obesity has led to an increased interest in pharmacological options to counteract excess weight gain. Gastrointestinal hormones such as glucagon, amylin, and glucagon-like peptide-1 (GLP-1) are well recognized for influencing food intake and satiety, but the therapeutic potential of these native peptides is overall limited by a short half-life and an often dose-dependent appearance of unwanted effects. Recent clinical success of chemically optimized GLP-1 mimetics with improved pharmacokinetics and sustained action has propelled pharmacological interest in using bioengineered gut hormones to treat obesity and diabetes. In this article, we summarize the basic biology and signaling mechanisms of selected gut peptides and discuss how they regulate systemic energy and glucose metabolism. Subsequently, we focus on the design and evaluation of unimolecular drugs that combine the beneficial effects of selected gut hormones into a single entity to optimize the beneficial impact on systems metabolism. © 2020 American Physiological Society. Compr Physiol 10:99-124, 2020.
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Affiliation(s)
- Gerald Grandl
- Institute for Diabetes and Obesity, Helmholtz Diabetes Center, Helmholtz Zentrum München - German Research Center for Environmental Health (GmbH), Neuherberg, Germany.,German Center for Diabetes Research (DZD), Neuherberg, Germany
| | - Aaron Novikoff
- Institute for Diabetes and Obesity, Helmholtz Diabetes Center, Helmholtz Zentrum München - German Research Center for Environmental Health (GmbH), Neuherberg, Germany.,German Center for Diabetes Research (DZD), Neuherberg, Germany
| | - Richard DiMarchi
- Department of Chemistry, Indiana University, Bloomington, Indiana, USA
| | - Matthias H Tschöp
- German Center for Diabetes Research (DZD), Neuherberg, Germany.,Division of Metabolic Diseases, Technische Universität München, Munich, Germany
| | - Timo D Müller
- Institute for Diabetes and Obesity, Helmholtz Diabetes Center, Helmholtz Zentrum München - German Research Center for Environmental Health (GmbH), Neuherberg, Germany.,German Center for Diabetes Research (DZD), Neuherberg, Germany.,Department of Pharmacology and Experimental Therapy, Institute of Experimental and Clinical Pharmacology and Toxicology, Eberhard Karls University Hospitals and Clinics, Tübingen, Germany
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29
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Hansen TT, Mead BR, García-Gavilán JF, Korndal SK, Harrold JA, Camacho-Barcía L, Ritz C, Christiansen P, Salas-Salvadó J, Hjorth MF, Blundell J, Bulló M, Halford JCG, Sjödin A. Is reduction in appetite beneficial for body weight management in the context of overweight and obesity? Yes, according to the SATIN (Satiety Innovation) study. J Nutr Sci 2019; 8:e39. [PMID: 32042406 PMCID: PMC6984007 DOI: 10.1017/jns.2019.36] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2019] [Accepted: 10/28/2019] [Indexed: 02/07/2023] Open
Abstract
New dietary-based concepts are needed for treatment and effective prevention of overweight and obesity. The primary objective was to investigate if reduction in appetite is associated with improved weight loss maintenance. This cohort study was nested within the European Commission project Satiety Innovation (SATIN). Participants achieving ≥8% weight loss during an initial 8-week low-energy formula diet were included in a 12-week randomised double-blind parallel weight loss maintenance intervention. The intervention included food products designed to reduce appetite or matching controls along with instructions to follow national dietary guidelines. Appetite was assessed by ad libitum energy intake and self-reported appetite evaluations using visual analogue scales during standardised appetite probe days. These were evaluated at the first day of the maintenance period compared with baseline (acute effects after a single exposure of intervention products) and post-maintenance compared with baseline (sustained effects after repeated exposures of intervention products) regardless of randomisation. A total of 181 participants (forty-seven men and 134 women) completed the study. Sustained reduction in 24-h energy intake was associated with improved weight loss maintenance (R 0·37; P = 0·001), whereas the association was not found acutely (P = 0·91). Suppression in self-reported appetite was associated with improved weight loss maintenance both acutely (R -0·32; P = 0·033) and sustained (R -0·33; P = 0·042). Reduction in appetite seems to be associated with improved body weight management, making appetite-reducing food products an interesting strategy for dietary-based concepts.
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Affiliation(s)
- Thea Toft Hansen
- Department of Nutrition, Exercise and Sports, Section for Obesity Research, Faculty of Science, University of Copenhagen, 1958 Copenhagen, Denmark
| | - Bethan R. Mead
- Department of Psychological Sciences, University of Liverpool, LiverpoolL69 7ZA, UK
| | - Jesús Francisco García-Gavilán
- Human Nutrition Unit, Faculty of Medicine and Health Sciences, Institut d'Investigació Sanitària Pere Virgili, Rovira i Virgili University, 43201Reus, Spain
- CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, 28029Madrid, Spain
| | - Sanne Kellebjerg Korndal
- Department of Nutrition, Exercise and Sports, Section for Obesity Research, Faculty of Science, University of Copenhagen, 1958 Copenhagen, Denmark
| | - Joanne A. Harrold
- Department of Psychological Sciences, University of Liverpool, LiverpoolL69 7ZA, UK
| | - Lucia Camacho-Barcía
- Human Nutrition Unit, Faculty of Medicine and Health Sciences, Institut d'Investigació Sanitària Pere Virgili, Rovira i Virgili University, 43201Reus, Spain
- CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, 28029Madrid, Spain
| | - Christian Ritz
- Department of Nutrition, Exercise and Sports, Section for Obesity Research, Faculty of Science, University of Copenhagen, 1958 Copenhagen, Denmark
| | - Paul Christiansen
- Department of Psychological Sciences, University of Liverpool, LiverpoolL69 7ZA, UK
| | - Jordi Salas-Salvadó
- Human Nutrition Unit, Faculty of Medicine and Health Sciences, Institut d'Investigació Sanitària Pere Virgili, Rovira i Virgili University, 43201Reus, Spain
- CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, 28029Madrid, Spain
| | - Mads Fiil Hjorth
- Department of Nutrition, Exercise and Sports, Section for Obesity Research, Faculty of Science, University of Copenhagen, 1958 Copenhagen, Denmark
| | - John Blundell
- Institute of Psychological Sciences, Faculty of Medicine and Health, University of Leeds, LeedsLS2 9JT, UK
| | - Mònica Bulló
- Human Nutrition Unit, Faculty of Medicine and Health Sciences, Institut d'Investigació Sanitària Pere Virgili, Rovira i Virgili University, 43201Reus, Spain
- CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, 28029Madrid, Spain
| | - Jason C. G. Halford
- Department of Psychological Sciences, University of Liverpool, LiverpoolL69 7ZA, UK
| | - Anders Sjödin
- Department of Nutrition, Exercise and Sports, Section for Obesity Research, Faculty of Science, University of Copenhagen, 1958 Copenhagen, Denmark
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Naseer F, Shabbir A, Livingstone B, Price R, Syn NL, Flannery O. The Efficacy of Energy-Restricted Diets in Achieving Preoperative Weight Loss for Bariatric Patients: a Systematic Review. Obes Surg 2019; 28:3678-3690. [PMID: 30121854 DOI: 10.1007/s11695-018-3451-1] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
In bariatric practice, a preoperative weight loss of at least 5% is recommended. However, the hypocaloric diets prescribed vary and no consensus exists. This study examined the efficacy of preoperative diets in achieving 5% weight loss. From a systematic literature search, eight randomised controlled trials (n = 862) were identified. Half of the trials used a "very-low-calorie diet" whilst the rest employed a "low-calorie diet". Only five diets achieved ≥ 5% weight loss over varying durations and energy intakes. By inference, compliance with a 700-1050 kcal (2929-4393 kJ) diet, consisting of moderate carbohydrate, high protein and low/moderate fat, for 3 weeks is likely to achieve 5% weight loss. A low-carbohydrate diet (< 20 g/day) may achieve this target within a shorter duration. Additional research is required to validate these conclusions.
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Affiliation(s)
- Fathimath Naseer
- Nutrition Innovation Centre for Food and Health, Ulster University, Cromore Road, Coleraine, Co. Londonderry, BT52 1SA, UK
| | - Asim Shabbir
- Department of Surgery, National University Hospital, 5 Lower Kent Ridge Road, Singapore, 119077, Singapore
- Yong Loo Lin School of Medicine, National University of Singapore, 21 Lower Kent Ridge Road, Singapore, 119077, Singapore
| | - Barbara Livingstone
- Nutrition Innovation Centre for Food and Health, Ulster University, Cromore Road, Coleraine, Co. Londonderry, BT52 1SA, UK
| | - Ruth Price
- Nutrition Innovation Centre for Food and Health, Ulster University, Cromore Road, Coleraine, Co. Londonderry, BT52 1SA, UK
| | - Nicholas L Syn
- Yong Loo Lin School of Medicine, National University of Singapore, 21 Lower Kent Ridge Road, Singapore, 119077, Singapore
| | - Orla Flannery
- Department of Clinical Sciences and Nutrition, University of Chester, Parkgate Road, Chester, CH1 4BJ, UK.
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31
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Sánchez-Alcoholado L, Gutiérrez-Repiso C, Gómez-Pérez AM, García-Fuentes E, Tinahones FJ, Moreno-Indias I. Gut microbiota adaptation after weight loss by Roux-en-Y gastric bypass or sleeve gastrectomy bariatric surgeries. Surg Obes Relat Dis 2019; 15:1888-1895. [PMID: 31648978 DOI: 10.1016/j.soard.2019.08.551] [Citation(s) in RCA: 58] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2019] [Revised: 07/19/2019] [Accepted: 08/31/2019] [Indexed: 01/21/2023]
Abstract
BACKGROUND Gut microbiota could be involved in the metabolic improvement after surgery. OBJECTIVE The aim of the present study was to evaluate the short-term evolution of the gut microbiome after different bariatric surgery procedures and their functionality and relate it with obesity resolution. SETTING University hospital, Spain. METHODS We studied 28 patients with severe obesity; 14 underwent a Roux-en-Y gastric bypass (RYGB) and 14 underwent laparoscopic sleeve gastrectomy (SG). All patients were examined before and 3 months after the correspondent bariatric surgery. Gut microbiome profile was assessed by the sequencing of amplicons from the 16S rDNA gene by next-generation sequencing. RESULTS Gut microbiota profiles significantly differed between surgical procedures. RYGB suffered the largest changes in the microbiota population. SG and RYGB differed in their profiles with higher levels of Akkermansia, Eubacterium, Haemophilus, and Blautia for SG, while Veillonella, Slackia, Granucatiella, and Acidaminococcus occurred with greater levels in RYGB. RYGB microbiota changes were reflected also at the level of functionality, especially in pathways related to environmental adaptation. A biomarker discovery analysis revealed the genus Blautia as characteristic in SG, while Veillonella was of RYGB. CONCLUSION Our study shows a shift of the gut microbiome after a bariatric surgery in a procedure-related manner. Gut microbiome changes are related to the adaptation to the changing gut environment and could be related to the pH fluctuations.
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Affiliation(s)
- Lidia Sánchez-Alcoholado
- Department of Endocrinology and Nutrition, Virgen de la Victoria University Hospital, Institute of Biomedical Research in Malaga (IBIMA) and University of Malaga, Malaga, Spain; Centro de Investigación Biomédica en Red de la Fisiopatología de la Obesidad y Nutrición (CIBEROBN CB06/003), Instituto de Salud Carlos III, Madrid, Spain
| | - Carolina Gutiérrez-Repiso
- Department of Endocrinology and Nutrition, Virgen de la Victoria University Hospital, Institute of Biomedical Research in Malaga (IBIMA) and University of Malaga, Malaga, Spain; Centro de Investigación Biomédica en Red de la Fisiopatología de la Obesidad y Nutrición (CIBEROBN CB06/003), Instituto de Salud Carlos III, Madrid, Spain
| | - Ana María Gómez-Pérez
- Department of Endocrinology and Nutrition, Virgen de la Victoria University Hospital, Institute of Biomedical Research in Malaga (IBIMA) and University of Malaga, Malaga, Spain
| | - Eduardo García-Fuentes
- Centro de Investigación Biomédica en Red de la Fisiopatología de la Obesidad y Nutrición (CIBEROBN CB06/003), Instituto de Salud Carlos III, Madrid, Spain; Department of Gastroenterology, Virgen de la Victoria University Hospital, Institute of Biomedical Research in Malaga (IBIMA) and University of Malaga, Malaga, Spain
| | - Francisco J Tinahones
- Department of Endocrinology and Nutrition, Virgen de la Victoria University Hospital, Institute of Biomedical Research in Malaga (IBIMA) and University of Malaga, Malaga, Spain; Centro de Investigación Biomédica en Red de la Fisiopatología de la Obesidad y Nutrición (CIBEROBN CB06/003), Instituto de Salud Carlos III, Madrid, Spain.
| | - Isabel Moreno-Indias
- Department of Endocrinology and Nutrition, Virgen de la Victoria University Hospital, Institute of Biomedical Research in Malaga (IBIMA) and University of Malaga, Malaga, Spain; Centro de Investigación Biomédica en Red de la Fisiopatología de la Obesidad y Nutrición (CIBEROBN CB06/003), Instituto de Salud Carlos III, Madrid, Spain.
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32
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Behary P, Tharakan G, Alexiadou K, Johnson N, Wewer Albrechtsen NJ, Kenkre J, Cuenco J, Hope D, Anyiam O, Choudhury S, Alessimii H, Poddar A, Minnion J, Doyle C, Frost G, Le Roux C, Purkayastha S, Moorthy K, Dhillo W, Holst JJ, Ahmed AR, Prevost AT, Bloom SR, Tan TM. Combined GLP-1, Oxyntomodulin, and Peptide YY Improves Body Weight and Glycemia in Obesity and Prediabetes/Type 2 Diabetes: A Randomized, Single-Blinded, Placebo-Controlled Study. Diabetes Care 2019; 42:1446-1453. [PMID: 31177183 DOI: 10.2337/dc19-0449] [Citation(s) in RCA: 85] [Impact Index Per Article: 14.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/05/2019] [Accepted: 04/25/2019] [Indexed: 02/06/2023]
Abstract
OBJECTIVE Roux-en-Y gastric bypass (RYGB) augments postprandial secretion of glucagon-like peptide 1 (GLP-1), oxyntomodulin (OXM), and peptide YY (PYY). Subcutaneous infusion of these hormones ("GOP"), mimicking postprandial levels, reduces energy intake. Our objective was to study the effects of GOP on glycemia and body weight when given for 4 weeks to patients with diabetes and obesity. RESEARCH DESIGN AND METHODS In this single-blinded mechanistic study, obese patients with prediabetes/diabetes were randomized to GOP (n = 15) or saline (n = 11) infusion for 4 weeks. We also studied 21 patients who had undergone RYGB and 22 patients who followed a very low-calorie diet (VLCD) as unblinded comparators. Outcomes measured were 1) body weight, 2) fructosamine levels, 3) glucose and insulin during a mixed meal test (MMT), 4) energy expenditure (EE), 5) energy intake (EI), and 6) mean glucose and measures of glucose variability during continuous glucose monitoring. RESULTS GOP infusion was well tolerated over the 4-week period. There was a greater weight loss (P = 0.025) with GOP (mean change -4.4 [95% CI -5.3, -3.5] kg) versus saline (-2.5 [-4.1, -0.9] kg). GOP led to a greater improvement (P = 0.0026) in fructosamine (-44.1 [-62.7, -25.5] µmol/L) versus saline (-11.7 [-18.9, -4.5] µmol/L). Despite a smaller weight loss compared with RYGB and VLCD, GOP led to superior glucose tolerance after a mixed-meal stimulus and reduced glycemic variability compared with RYGB and VLCD. CONCLUSIONS GOP infusion improves glycemia and reduces body weight. It achieves superior glucose tolerance and reduced glucose variability compared with RYGB and VLCD. GOP is a viable alternative for the treatment of diabetes with favorable effects on body weight.
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Affiliation(s)
- Preeshila Behary
- Section of Investigative Medicine, Imperial College London, London, U.K
| | - George Tharakan
- Section of Investigative Medicine, Imperial College London, London, U.K
| | | | - Nicholas Johnson
- Imperial Clinical Trials Unit, Imperial College London, London, U.K
| | - Nicolai J Wewer Albrechtsen
- Department of Clinical Biochemistry, Rigshospitalet, Copenhagen, Denmark.,Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Julia Kenkre
- Section of Investigative Medicine, Imperial College London, London, U.K
| | - Joyceline Cuenco
- Section of Investigative Medicine, Imperial College London, London, U.K
| | - David Hope
- Section of Investigative Medicine, Imperial College London, London, U.K
| | - Oluwaseun Anyiam
- Section of Investigative Medicine, Imperial College London, London, U.K
| | - Sirazum Choudhury
- Section of Investigative Medicine, Imperial College London, London, U.K
| | - Haya Alessimii
- Section of Investigative Medicine, Imperial College London, London, U.K
| | - Ankur Poddar
- Section of Investigative Medicine, Imperial College London, London, U.K
| | - James Minnion
- Section of Investigative Medicine, Imperial College London, London, U.K
| | - Chedie Doyle
- Section of Investigative Medicine, Imperial College London, London, U.K
| | - Gary Frost
- Section of Investigative Medicine, Imperial College London, London, U.K
| | - Carel Le Roux
- Section of Investigative Medicine, Imperial College London, London, U.K.,School of Medicine, University College Dublin, Dublin, Ireland
| | - Sanjay Purkayastha
- Department of Surgery and Cancer, Imperial College Healthcare National Health Service Trust, London, U.K
| | - Krishna Moorthy
- Department of Surgery and Cancer, Imperial College Healthcare National Health Service Trust, London, U.K
| | - Waljit Dhillo
- Section of Investigative Medicine, Imperial College London, London, U.K
| | - Jens J Holst
- Panum Institute, Department of Biomedical Sciences and the Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark
| | - Ahmed R Ahmed
- Department of Surgery and Cancer, Imperial College Healthcare National Health Service Trust, London, U.K
| | - A Toby Prevost
- Imperial Clinical Trials Unit, Imperial College London, London, U.K
| | - Stephen R Bloom
- Section of Investigative Medicine, Imperial College London, London, U.K
| | - Tricia M Tan
- Section of Investigative Medicine, Imperial College London, London, U.K.
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Bypassed and Preserved Stomach Resulted in Superior Glucose Control in Sprague-Dawley Rats with Streptozotocin-Induced Diabetes. Sci Rep 2019; 9:9981. [PMID: 31292518 PMCID: PMC6620334 DOI: 10.1038/s41598-019-46418-y] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2018] [Accepted: 06/28/2019] [Indexed: 12/18/2022] Open
Abstract
Recent studies suggest the possibility of the stomach playing a role in diabetes remission after bariatric surgery. In this study, we investigated whether bypassing the stomach alleviates diabetes in diabetic rodent model. Eighteen moderately obese and diabetic Sprague-Dawley rats were randomly assigned to Esophagoduodenostomy with or without gastric preservation (EDG and EDNG/total gastrectomy, respectively), and SHAM groups. Bodyweight, food intake, fasting glucose level, oral glucose tolerance test result (OGTT), and hormone levels (insulin, glucagon-like peptide-1, ghrelin, gastrin and glucagon) were measured preoperative and postoperatively. Postoperatively, bodyweight and food intake did not differ significantly between the EDG and EDNG groups. Postoperative fasting blood glucose and OGTT results declined significantly in the EDG and EDNG group when compared with the respective preoperative levels. Postoperative glucose control improvements in EDNG group was significantly inferior when compared to EDG. Compared preoperatively, postoperative plasma ghrelin and gastrin levels declined significantly in EDNG group. Preoperative and postoperative plasma GLP-1 level did not differ significantly among all the groups. Postoperatively, EDG group had significantly higher insulin and lower glucagon levels when compared with SHAM. In conclusion, bypassing and preserving the stomach resulted in superior glucose control improvements than total gastrectomy.
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Hansen TT, Andersen SV, Astrup A, Blundell J, Sjödin A. Is reducing appetite beneficial for body weight management in the context of overweight and obesity? A systematic review and meta-analysis from clinical trials assessing body weight management after exposure to satiety enhancing and/or hunger reducing products. Obes Rev 2019; 20:983-997. [PMID: 30945414 DOI: 10.1111/obr.12854] [Citation(s) in RCA: 27] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/05/2019] [Revised: 02/25/2019] [Accepted: 03/04/2019] [Indexed: 01/11/2023]
Abstract
This review aims to investigate whether interventions that enhance satiety and/or reduce hunger lead to beneficial effects on body weight management in the context of overweight and obesity. A comprehensive review protocol was prepared before conducting a systematic search in PubMed identifying 517 papers with 12 meeting the inclusion criteria. A thorough risk of bias assessment was performed based on the Cochrane collaboration's tool for assessing risk of bias. Based on a meta-analysis, the average of 75 subjects exposed to satiety enhancing and/or hunger reducing foods during more than 8 weeks coincidently reduced their body weight by 3.60 (1.05; 6.15) kg (mean (95% confidence interval)) more compared with controls. Two studies analysed whether individual reductions in appetite were associated with body weight. Decreased ad libitum energy intake after exposure to the satiety enhancing and/or hunger reducing interventions explained 58% (P < 0.001) and 23% (P < 0.001) of the variations in the subsequent weight losses over 12 and 8 weeks, respectively. Robust acute effects on appetite were found equally likely to be linked to improved body weight management as sustained effects. Satiety enhancing and/or hunger reducing interventions are supported to improve body weight management, but studies specifically designed to demonstrate a causal link remain needed.
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Affiliation(s)
- Thea Toft Hansen
- Department of Nutrition, Exercise and Sports, Section for Obesity Research, Faculty of Science, University of Copenhagen, Denmark
| | - Sarah Vold Andersen
- Department of Nutrition, Exercise and Sports, Section for Obesity Research, Faculty of Science, University of Copenhagen, Denmark
| | - Arne Astrup
- Department of Nutrition, Exercise and Sports, Section for Obesity Research, Faculty of Science, University of Copenhagen, Denmark
| | - John Blundell
- Institute of Psychological Sciences, Faculty of Medicine and Health, University of Leeds, Leeds, UK
| | - Anders Sjödin
- Department of Nutrition, Exercise and Sports, Section for Obesity Research, Faculty of Science, University of Copenhagen, Denmark
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35
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Novaes Ravelli M, Schoeller DA, Crisp AH, Shriver T, Ferriolli E, Ducatti C, Marques de Oliveira MR. Influence of Energy Balance on the Rate of Weight Loss Throughout One Year of Roux-en-Y Gastric Bypass: a Doubly Labeled Water Study. Obes Surg 2019; 29:3299-3308. [PMID: 31230202 DOI: 10.1007/s11695-019-03989-z] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
OBJECTIVE To investigate the influence of changes in energy balance and body composition on the rate of weight loss throughout 1 year of Roux-en-Y gastric bypass. METHODS Variables were collected pre-, 6, and 12 months (M) post-surgery from 18 women (BMI ≥ 40 and ≤ 50 kg m-2, 20 to 45 years). Total energy expenditure (TEEm), fat-free mass (FFM), and fat mass (FM) were measured by doubly labeled water. Self-reported energy intake (EIsr) was obtained from three non-consecutive food diaries. Metabolic adaptation was assessed via deviations from TEE predictive equation, and the calculated energy intake (EIc) via the sum of TEE and change in body stores. RESULTS BMI significantly decreased (mean ± SD) from 45 ± 2 kg m-2 to 32 ± 3 kg m-2 at 6 M, and to 30 ± 3 kg m-2 at 12 M after surgery. The TEEm reduced significantly at both time points when compared with pre-surgery (6 M: - 612 ± 317 kcal day-1; 12 M: - 447 ± 516 kcal day-1). At 6 M, a metabolic adaptation was observed and the energy balance was - 1151 ± 195 kcal day-1, while at 12 M it was - 332 ± 158 kcal day-1. Changes in the values of TEEm were associated with changes in body weight at 12 M post-surgery. A significant underreporting was observed for EIsr (1057 ± 385 kcal day-1) vs. EIc (2083 ± 309 kcal day-1) at 12 M post-operative. CONCLUSION The higher rate of weight loss at 6 M post-surgery was a response to energy imbalance, which was caused by high restriction in energy intake even with the presence of metabolic adaptation at this time. The EIsr was not sufficiently accurate to assess the energy consumption of this population. REGISTRATION OF CLINICAL TRIALS (OBSERVATIONAL STUDY) Brazilian Clinical Trials Registry: RBR-8k5jsj. Universal Trial Number: U1111-1206-0858.
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Affiliation(s)
- Michele Novaes Ravelli
- School of Pharmaceutical Sciences, Sao Paulo State University - UNESP, Rodovia Araraquara Jaú, Km 01, s/n. Bairro: Campos Ville, Araraquara, SP, 14800-903, Brazil. .,Department of Neurology, University of Wisconsin - Madison, 1685 Highland Avenue, Medical Foundation Centennial Building, 7th Floor, Madison, WI, 53705, USA.
| | - Dale A Schoeller
- Biotechnology Center, University of Wisconsin - Madison, 425 Henry Mall Street, Madison, WI, 53706, USA
| | - Alex Harley Crisp
- School of Pharmaceutical Sciences, Sao Paulo State University - UNESP, Rodovia Araraquara Jaú, Km 01, s/n. Bairro: Campos Ville, Araraquara, SP, 14800-903, Brazil
| | - Timothy Shriver
- Biotechnology Center, University of Wisconsin - Madison, 425 Henry Mall Street, Madison, WI, 53706, USA
| | - Eduardo Ferriolli
- Ribeirao Preto Medical School, University of Sao Paulo - USP, Avenida Bandeirantes, 3900 - Bairro: Monte Alegre, Ribeirão Preto, SP, 14049-900, Brazil
| | - Carlos Ducatti
- Stable Isotope Center, Bioscience Institute, Sao Paulo State University - UNESP, Rua Prof. Dr. Antônio Celso Wagner Zanin, 250 - Bairro: Distrito de Rubião Junior, Botucatu, SP, 18618-689, Brazil
| | - Maria Rita Marques de Oliveira
- Education Department, Institute of Biosciences, Sao Paulo State University - UNESP, Rua Prof. Dr. Antônio Celso Wagner Zanin, 250 - Bairro: Distrito de Rubião Junior, Botucatu, SP, 18618-689, Brazil
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36
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Halliday TM, Polsky S, Schoen JA, Legget KT, Tregellas JR, Williamson KM, Cornier M. Comparison of surgical versus diet-induced weight loss on appetite regulation and metabolic health outcomes. Physiol Rep 2019; 7:e14048. [PMID: 30927343 PMCID: PMC6440915 DOI: 10.14814/phy2.14048] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2018] [Revised: 03/06/2019] [Accepted: 03/07/2019] [Indexed: 12/15/2022] Open
Abstract
Bariatric surgery is associated with significant and sustained weight loss and improved metabolic outcomes. It is unclear if weight loss alone is the main mechanism of improved metabolic health. The purpose of this trial was to compare indices of appetite regulation, insulin sensitivity and energy intake (EI) between participants achieving 10 kg of weight loss via Roux-en-Y Gastric Bypass (RYGB) or dietary restriction (DIET); intake of a very low calorie liquid diet (800 kcal/d; 40% protein, 40% fat, 20% carbohydrate that matched the post-RYGB dietary protocol). Adults qualifying for bariatric surgery were studied before and after 10 kg of weight loss (RYGB [n = 6]) or DIET [n = 17]). Appetite (hunger, satiety, and prospective food consumption [PFC]), appetite-related hormones, and metabolites (ghrelin, PYY, GLP-1, insulin, glucose, free fatty acids [FFA], and triglycerides [TG]) were measured in the fasting state and every 30 min for 180 min following breakfast. Participants were provided lunch to evaluate acute ad libitum EI, which was similarly reduced in both groups from pre to post weight loss. Fasting ghrelin was reduced to a greater extent following RYGB compared to DIET (P = 0.04). Area under the curve (AUC) for ghrelin (P = 0.01), hunger (P < 0.01) and PFC (P < 0.01) increased after DIET compared to RYGB, following 10 kg weight loss. Satiety AUC increased after RYGB and decreased after DIET (P < 0.01). Glucose and insulin (fasting and AUC) decreased in both groups. FFA increased in both groups, with a greater increase in AUC seen after RYGB versus DIET (P = 0.02). In summary, appetite-related indices were altered in a manner that, if maintained, may promote a sustained reduction in energy intake with RYGB compared to DIET. Future work with a larger sample size and longer follow-up will be important to confirm and extend these findings.
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Affiliation(s)
- Tanya M. Halliday
- Division of Endocrinology, Metabolism and DiabetesUniversity of Colorado School of MedicineAnschutz Medical CampusAuroraColorado
- Department of Health, Kinesiology, and RecreationUniversity of UtahSalt Lake CityUtah
| | - Sarit Polsky
- Barbara Davis Center for DiabetesUniversity of Colorado School of MedicineAnschutz Medical CampusAuroraColorado
| | - Jonathan A. Schoen
- Division of GI, Tumor and Endocrine SurgeryUniversity of Colorado School of MedicineAnschutz Medical CampusAuroraColorado
| | - Kristina T. Legget
- Division of PsychiatryUniversity of Colorado School of MedicineAnschutz Medical CampusAuroraColorado
| | - Jason R. Tregellas
- Division of PsychiatryUniversity of Colorado School of MedicineAnschutz Medical CampusAuroraColorado
| | - Kayla M. Williamson
- Department of Biostatistics and InformaticsColorado School of Public HealthUniversity of ColoradoAnschutz Medical CampusAuroraColorado
| | - Marc‐Andre Cornier
- Division of Endocrinology, Metabolism and DiabetesUniversity of Colorado School of MedicineAnschutz Medical CampusAuroraColorado
- Anschutz Health and Wellness CenterUniversity of Colorado School of MedicineAnschutz Medical CampusAuroraColorado
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37
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Coen PM, Carnero EA, Goodpaster BH. Exercise and Bariatric Surgery: An Effective Therapeutic Strategy. Exerc Sport Sci Rev 2018; 46:262-270. [PMID: 30052546 PMCID: PMC6147093 DOI: 10.1249/jes.0000000000000168] [Citation(s) in RCA: 38] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Exercise is a clinically effective adjunct therapy with the potential to promote long-term weight loss maintenance for bariatric surgery patients. The long-term efficacy of bariatric surgery is not entirely clear, and weight regain and diabetes relapse are problems for some patients. Exercise is a feasible and clinically effective adjunct therapy for bariatric surgery patients. We hypothesize that exercise is also a critical factor for long-term weight loss maintenance and lasting remission of type 2 diabetes.
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Affiliation(s)
- Paul M Coen
- Translational Research Institute for Metabolism and Diabetes, Florida Hospital.,Sanford Burnham Prebys Medical Discovery Institute at Lake Nona, Orlando, FL
| | - Elvis A Carnero
- Translational Research Institute for Metabolism and Diabetes, Florida Hospital
| | - Bret H Goodpaster
- Translational Research Institute for Metabolism and Diabetes, Florida Hospital.,Sanford Burnham Prebys Medical Discovery Institute at Lake Nona, Orlando, FL
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38
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Müller TD, Clemmensen C, Finan B, DiMarchi RD, Tschöp MH. Anti-Obesity Therapy: from Rainbow Pills to Polyagonists. Pharmacol Rev 2018; 70:712-746. [PMID: 30087160 DOI: 10.1124/pr.117.014803] [Citation(s) in RCA: 131] [Impact Index Per Article: 18.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
With their ever-growing prevalence, obesity and diabetes represent major health threats of our society. Based on estimations by the World Health Organization, approximately 300 million people will be obese in 2035. In 2015 alone there were more than 1.6 million fatalities attributable to hyperglycemia and diabetes. In addition, treatment of these diseases places an enormous burden on our health care system. As a result, the development of pharmacotherapies to tackle this life-threatening pandemic is of utmost importance. Since the beginning of the 19th century, a variety of drugs have been evaluated for their ability to decrease body weight and/or to improve deranged glycemic control. The list of evaluated drugs includes, among many others, sheep-derived thyroid extracts, mitochondrial uncouplers, amphetamines, serotonergics, lipase inhibitors, and a variety of hormones produced and secreted by the gastrointestinal tract or adipose tissue. Unfortunately, when used as a single hormone therapy, most of these drugs are underwhelming in their efficacy or safety, and placebo-subtracted weight loss attributed to such therapy is typically not more than 10%. In 2009, the generation of a single molecule with agonism at the receptors for glucagon and the glucagon-like peptide 1 broke new ground in obesity pharmacology. This molecule combined the beneficial anorectic and glycemic effects of glucagon-like peptide 1 with the thermogenic effect of glucagon into a single molecule with enhanced potency and sustained action. Several other unimolecular dual agonists have subsequently been developed, and, based on their preclinical success, these molecules illuminate the path to a new and more fruitful era in obesity pharmacology. In this review, we focus on the historical pharmacological approaches to treat obesity and glucose intolerance and describe how the knowledge obtained by these studies led to the discovery of unimolecular polypharmacology.
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Affiliation(s)
- T D Müller
- Institute for Diabetes and Obesity, Helmholtz Diabetes Center, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany (T.D.M., C.C., M.H.T.); German Center for Diabetes Research, Neuherberg, Germany (T.D.M., C.C., M.H.T.); Department of Chemistry, Indiana University, Bloomington, Indiana (B.F., R.D.D.); and Division of Metabolic Diseases, Technische Universität München, Munich, Germany (M.H.T.)
| | - C Clemmensen
- Institute for Diabetes and Obesity, Helmholtz Diabetes Center, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany (T.D.M., C.C., M.H.T.); German Center for Diabetes Research, Neuherberg, Germany (T.D.M., C.C., M.H.T.); Department of Chemistry, Indiana University, Bloomington, Indiana (B.F., R.D.D.); and Division of Metabolic Diseases, Technische Universität München, Munich, Germany (M.H.T.)
| | - B Finan
- Institute for Diabetes and Obesity, Helmholtz Diabetes Center, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany (T.D.M., C.C., M.H.T.); German Center for Diabetes Research, Neuherberg, Germany (T.D.M., C.C., M.H.T.); Department of Chemistry, Indiana University, Bloomington, Indiana (B.F., R.D.D.); and Division of Metabolic Diseases, Technische Universität München, Munich, Germany (M.H.T.)
| | - R D DiMarchi
- Institute for Diabetes and Obesity, Helmholtz Diabetes Center, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany (T.D.M., C.C., M.H.T.); German Center for Diabetes Research, Neuherberg, Germany (T.D.M., C.C., M.H.T.); Department of Chemistry, Indiana University, Bloomington, Indiana (B.F., R.D.D.); and Division of Metabolic Diseases, Technische Universität München, Munich, Germany (M.H.T.)
| | - M H Tschöp
- Institute for Diabetes and Obesity, Helmholtz Diabetes Center, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany (T.D.M., C.C., M.H.T.); German Center for Diabetes Research, Neuherberg, Germany (T.D.M., C.C., M.H.T.); Department of Chemistry, Indiana University, Bloomington, Indiana (B.F., R.D.D.); and Division of Metabolic Diseases, Technische Universität München, Munich, Germany (M.H.T.)
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39
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Hao Z, Leigh Townsend R, Mumphrey MB, Gettys TW, Yu S, Münzberg H, Morrison CD, Berthoud HR. Roux-en-Y Gastric Bypass Surgery-Induced Weight Loss and Metabolic Improvements Are Similar in TGR5-Deficient and Wildtype Mice. Obes Surg 2018; 28:3227-3236. [PMID: 29770924 PMCID: PMC6153575 DOI: 10.1007/s11695-018-3297-6] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
BACKGROUND AND PURPOSE Roux-en-Y gastric bypass surgery (RYGB) remains one of the most effective treatments for obesity and type 2 diabetes. Despite this, the mechanisms through which it acts are still not well understood. Bile acid signaling through the transmembrane G-protein-coupled receptor TGR5 has been shown to have significant effects on metabolism and has recently been reported to be necessary for the full effects of vertical sleeve gastrectomy (VSG), a bariatric surgery with similar effects to RYGB. The goal of the current study is therefore to investigate the role of bile acid signaling through TGR5 to see if it is necessary to obtain the full effects of RYGB. METHODS High-fat diet-induced obese TGR5-/- and wildtype mice (WT) were subjected to RYGB, sham surgery, or weight matching (WM) to RYGB mice via caloric restriction. Body weight, body composition, food intake, energy expenditure, glucose tolerance, insulin sensitivity, and liver weight were measured. RESULTS Although the difference in fat mass 20 weeks after surgery between RYGB and sham-operated mice was slightly reduced in TGR5-/- mice when compared to wildtype mice, loss of body weight and fat mass from preoperative levels, reduction of food intake, increase of energy expenditure, and improvement in glycemic control were similar in the two genotypes. Furthermore, improvements in glycemic control were similar in non-surgical mice weight-matched to RYGB. CONCLUSIONS We conclude that bile acid signaling through TGR5 is not required for the beneficial effects of RYGB in the mouse and that RYGB and VSG may achieve their similar beneficial effects through different mechanisms.
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Affiliation(s)
- Zheng Hao
- Neurobiology of Nutrition & Metabolism Department, Pennington Biomedical Research Center, Louisiana State University System, 6400 Perkins Road, Baton Rouge, LA, 70808, USA
| | - R Leigh Townsend
- Neurobiology of Nutrition & Metabolism Department, Pennington Biomedical Research Center, Louisiana State University System, 6400 Perkins Road, Baton Rouge, LA, 70808, USA
| | - Michael B Mumphrey
- Neurobiology of Nutrition & Metabolism Department, Pennington Biomedical Research Center, Louisiana State University System, 6400 Perkins Road, Baton Rouge, LA, 70808, USA
| | - Thomas W Gettys
- Nutrient Sensing and Adipocyte Signaling Laboratory, Pennington Biomedical Research Center, Louisiana State University System, Baton Rouge, LA, USA
| | - Sangho Yu
- Neurobiology of Nutrition & Metabolism Department, Pennington Biomedical Research Center, Louisiana State University System, 6400 Perkins Road, Baton Rouge, LA, 70808, USA
| | - Heike Münzberg
- Neurobiology of Nutrition & Metabolism Department, Pennington Biomedical Research Center, Louisiana State University System, 6400 Perkins Road, Baton Rouge, LA, 70808, USA
| | - Christopher D Morrison
- Neurobiology of Nutrition & Metabolism Department, Pennington Biomedical Research Center, Louisiana State University System, 6400 Perkins Road, Baton Rouge, LA, 70808, USA
| | - Hans-Rudolf Berthoud
- Neurobiology of Nutrition & Metabolism Department, Pennington Biomedical Research Center, Louisiana State University System, 6400 Perkins Road, Baton Rouge, LA, 70808, USA.
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40
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Ahuja A, Tantia O, Goyal G, Chaudhuri T, Khanna S, Poddar A, Gupta S, Majumdar K. Reply to: Yet Another Mortality with a Bilio-Pancreatic Limb of > 200 cm with One Anastomosis Gastric Bypass. Obes Surg 2018; 28:3636-3637. [PMID: 30112602 DOI: 10.1007/s11695-018-3463-x] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/28/2022]
Affiliation(s)
- Anmol Ahuja
- Department of Minimal Access & Bariatric Surgery, ILS Hospitals, DD-6, Sector 1, Salt Lake City, Kolkata, West Bengal, 700064, India
| | - Om Tantia
- Department of Minimal Access & Bariatric Surgery, ILS Hospitals, DD-6, Sector 1, Salt Lake City, Kolkata, West Bengal, 700064, India.
| | - Ghanshyam Goyal
- Department of Minimal Access & Bariatric Surgery, ILS Hospitals, DD-6, Sector 1, Salt Lake City, Kolkata, West Bengal, 700064, India
| | - Tamonas Chaudhuri
- Department of Minimal Access & Bariatric Surgery, ILS Hospitals, DD-6, Sector 1, Salt Lake City, Kolkata, West Bengal, 700064, India
| | - Shashi Khanna
- Department of Minimal Access & Bariatric Surgery, ILS Hospitals, DD-6, Sector 1, Salt Lake City, Kolkata, West Bengal, 700064, India
| | - Anshuman Poddar
- Department of Minimal Access & Bariatric Surgery, ILS Hospitals, DD-6, Sector 1, Salt Lake City, Kolkata, West Bengal, 700064, India
| | - Sonam Gupta
- Department of Minimal Access & Bariatric Surgery, ILS Hospitals, DD-6, Sector 1, Salt Lake City, Kolkata, West Bengal, 700064, India
| | - Kajari Majumdar
- Department of Minimal Access & Bariatric Surgery, ILS Hospitals, DD-6, Sector 1, Salt Lake City, Kolkata, West Bengal, 700064, India
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41
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Ravelli MN, Schoeller DA, Crisp AH, Racine NM, Pfrimer K, Rasera Junior I, Oliveira MRMD. Accuracy of total energy expenditure predictive equations after a massive weight loss induced by bariatric surgery. Clin Nutr ESPEN 2018; 26:57-65. [PMID: 29908684 DOI: 10.1016/j.clnesp.2018.04.013] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2018] [Accepted: 04/18/2018] [Indexed: 12/31/2022]
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42
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Brandt SJ, Kleinert M, Tschöp MH, Müller TD. Are peptide conjugates the golden therapy against obesity? J Endocrinol 2018; 238:R109-R119. [PMID: 29848610 PMCID: PMC6026923 DOI: 10.1530/joe-18-0264] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/27/2018] [Accepted: 05/30/2018] [Indexed: 12/19/2022]
Abstract
Obesity is a worldwide pandemic, which can be fatal for the most extremely affected individuals. Lifestyle interventions such as diet and exercise are largely ineffective and current anti-obesity medications offer little in the way of significant or sustained weight loss. Bariatric surgery is effective, but largely restricted to only a small subset of extremely obese patients. While the hormonal factors mediating sustained weight loss and remission of diabetes by bariatric surgery remain elusive, a new class of polypharmacological drugs shows potential to shrink the gap in efficacy between a surgery and pharmacology. In essence, this new class of drugs combines the beneficial effects of several independent hormones into a single entity, thereby combining their metabolic efficacy to improve systems metabolism. Such unimolecular drugs include single molecules with agonism at the receptors for glucagon, glucagon-like peptide 1 and the glucose-dependent insulinotropic polypeptide. In preclinical studies, these specially tailored multiagonists outperform both their mono-agonist components and current best in class anti-obesity medications. While clinical trials and vigorous safety analyses are ongoing, these drugs are poised to have a transformative effect in anti-obesity therapy and might hopefully lead the way to a new era in weight-loss pharmacology.
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Affiliation(s)
- S J Brandt
- Institute for Diabetes and ObesityHelmholtz Diabetes Center, Helmholtz Zentrum München, German Research Center for Environmental Health (GmbH), Neuherberg, Germany
- German Center for Diabetes Research (DZD)Neuherberg, Germany
| | - M Kleinert
- Institute for Diabetes and ObesityHelmholtz Diabetes Center, Helmholtz Zentrum München, German Research Center for Environmental Health (GmbH), Neuherberg, Germany
- German Center for Diabetes Research (DZD)Neuherberg, Germany
| | - M H Tschöp
- Institute for Diabetes and ObesityHelmholtz Diabetes Center, Helmholtz Zentrum München, German Research Center for Environmental Health (GmbH), Neuherberg, Germany
- German Center for Diabetes Research (DZD)Neuherberg, Germany
- Division of Metabolic DiseasesTechnische Universität, Munich, Germany
| | - T D Müller
- Institute for Diabetes and ObesityHelmholtz Diabetes Center, Helmholtz Zentrum München, German Research Center for Environmental Health (GmbH), Neuherberg, Germany
- German Center for Diabetes Research (DZD)Neuherberg, Germany
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43
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Nemati R, Lu J, Dokpuang D, Booth M, Plank LD, Murphy R. Increased Bile Acids and FGF19 After Sleeve Gastrectomy and Roux-en-Y Gastric Bypass Correlate with Improvement in Type 2 Diabetes in a Randomized Trial. Obes Surg 2018; 28:2672-2686. [PMID: 29987678 DOI: 10.1007/s11695-018-3216-x] [Citation(s) in RCA: 68] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
BACKGROUND Sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB) are both effective bariatric procedures to treat type 2 diabetes (T2DM) and obesity. The contribution of changes in bile acids (BAs) and fibroblast growth factor19 (FGF19) to such metabolic improvements is unclear. METHODS We examined associations between changes in BAs, FGF19 (fasting and prandial), with changes in body weight, glycemia, and other metabolic variables in 61 obese patients with T2DM before and 1 year after randomization to SG or RYGB. RESULTS Weight loss and diabetes remission (defined by HbA1c < 39 mmol/mol [< 5.7%] in the absence of glucose-lowering therapy) after RYGB and SG was similar (mean weight loss - 29 vs - 31 kg, p = 0.50; diabetes remission proportion 37.5 vs 34%, p = 1.0). Greater increments in fasting and prandial levels of total, secondary, and unconjugated BAs were seen after RYGB than SG. Fasting and prandial increases in total (r = - 0.3, p = 0.01; r = - 0.2, p = 0.04), secondary (r = - 0.3, p = 0.01; r = - 0.4, p = 0.01) and unconjugated BA (r = - 0.3, p = 0.01; r = 0.4, p < 0.01) correlated with decreases in HbA1c, but not weight. Changes in 12α-OH/non 12α-OH were positively associated with prandial glucose increments (r = 0.2, p = 0.03), HbA1c (r = 0.3, p = 0.01), and negatively associated with changes in insulinogenc index (r = - 0.3, p = 0.01). Only changes in prandial FGF19 were negatively associated with HbA1c (r = - 0.4, p < 0.01) and visceral fat (r = - 0.3, p = 0.04). CONCLUSIONS/INTERPRETATION The association between increases in secondary, unconjugated BAs and improvements in HBA1c (but not weight) achieved after both RYGB and SG suggest manipulation of BA as a potential strategy for controlling T2DM through weight-independent means.
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Affiliation(s)
- Reza Nemati
- School of Science, Faculty of Health and Environmental Sciences, Auckland University of Technology, Private Bag 92006, Auckland, 1142, New Zealand
| | - Jun Lu
- School of Science, Faculty of Health and Environmental Sciences, Auckland University of Technology, Private Bag 92006, Auckland, 1142, New Zealand. .,College of Life and Marine Sciences, Shenzhen University, Shenzhen, Guangdong Province, China. .,School of Interprofessional Health Studies, Faculty of Health and Environmental Sciences, Auckland University of Technology, Auckland, New Zealand. .,Institute of Biomedical Technology, Auckland University of Technology, Auckland, New Zealand.
| | - Dech Dokpuang
- School of Science, Faculty of Health and Environmental Sciences, Auckland University of Technology, Private Bag 92006, Auckland, 1142, New Zealand.,Division of Medical Technology, School of Allied Health Sciences, University of Phayao, Phayao, Thailand
| | - Michael Booth
- Department of Surgery, North Shore Hospital, Waitemata District Health Board, Auckland, New Zealand
| | - Lindsay D Plank
- Department of Surgery, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand
| | - Rinki Murphy
- Auckland Diabetes Centre, Auckland District Health Board, Auckland, New Zealand. .,Whitiora Diabetes Department, Counties Manukau District Health Board, Auckland, New Zealand. .,Department of Medicine, Faculty of Medical and Health Sciences, University of Auckland, Private Bag 92019, Auckland, 1142, New Zealand. .,Maurice Wilkins Centre for Biodiscovery, Auckland, New Zealand.
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44
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Affiliation(s)
- John P Kirwan
- Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, LA
| | - Heike Münzberg
- Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, LA
| | - Hans-Rudolf Berthoud
- Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, LA
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45
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van den Broek M, de Heide LJM, Emous M, Wijma RB, Veeger NJGM, Wolthuis A, Laskewitz AJ, Heiner-Fokkema MR, Muller Kobold AC, Wolffenbuttel BHR, van Beek AP. Satiety and gastrointestinal hormones during a Mixed Meal Tolerance Test after gastric bypass surgery: association with plasma amino acid concentrations. Surg Obes Relat Dis 2018; 14:1106-1117. [PMID: 29937240 DOI: 10.1016/j.soard.2018.05.010] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2018] [Revised: 04/23/2018] [Accepted: 05/14/2018] [Indexed: 01/06/2023]
Abstract
BACKGROUND Circulating amino acids have been associated with both appetite and the secretion of anorexigenic hormones in healthy and obese populations. This effect has not been investigated in subjects having undergone Roux-en-Y gastric bypass surgery (RYGB). OBJECTIVE To investigate the association between postprandial plasma concentrations of amino acids and the anorexigenic hormones glucagon-like peptide-1 (GLP-1) and peptide tyrosine tyrosine (PYY), the orexigenic hormone ghrelin, and satiety and hunger in post-RYGB subjects. SETTING A Dutch surgical department. METHODS Participants after primary RYGB were studied during a Mixed Meal Tolerance Test (MMTT). Satiety and hunger were assessed every 30 minutes on visual analogue scales. Blood samples were collected at baseline, every 10 minutes during the first half hour and every 30 minutes until 210 minutes after the start. The samples were assessed for 24 amino acids and 3 gastrointestinal hormones. Incremental areas under the curve (iAUCs) were calculated. Exploratory analyses were performed in which subjects were divided into high and low responders depending on the median iAUC. RESULTS 42 subjects, aged 48 ± 11 (mean ± SD) years, 31 to 76 months post-RYGB and with total weight loss of 30 ± 9% completed the MMTT. Subjects with high satiety scores had more than a 25% higher net iAUC of PYY and GLP-1 and at least a 10% higher net iAUC of 10 amino acids compared to subjects with low scores (P < 0.05). The net iAUC of five of these amino acids (i.e. arginine, asparagine, histidine, serine and threonine) was more than 10% higher in subjects with high responses on GLP-1 and/or PYY (P < 0.05). CONCLUSIONS Certain postprandial amino acids were associated with satiety and anorexigenic hormones and could therefore play a role in appetite regulation after RYGB; either by a direct effect on satiety, indirectly through gastrointestinal hormones, or both.
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Affiliation(s)
- Merel van den Broek
- Department of Internal Medicine, Medical Center Leeuwarden, Leeuwarden, The Netherlands.
| | - Loek J M de Heide
- Department of Internal Medicine, Medical Center Leeuwarden, Leeuwarden, The Netherlands
| | - Marloes Emous
- Department of Surgery, Medical Center Leeuwarden, Leeuwarden, The Netherlands; Centre for Obesity Netherlands (CON), Medical Center Leeuwarden, Leeuwarden, The Netherlands
| | - Ragnhild B Wijma
- Department of Surgery, Medical Center Leeuwarden, Leeuwarden, The Netherlands; Centre for Obesity Netherlands (CON), Medical Center Leeuwarden, Leeuwarden, The Netherlands
| | - Nic J G M Veeger
- Department of Epidemiology, Medical Center Leeuwarden, Leeuwarden, The Netherlands; Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | - Albert Wolthuis
- Department of Clinical Chemistry, CERTE, Medical Center Leeuwarden, Leeuwarden, The Netherlands
| | - Anke J Laskewitz
- Department of Clinical Chemistry, CERTE, Medical Center Leeuwarden, Leeuwarden, The Netherlands
| | - M Rebecca Heiner-Fokkema
- Department of Laboratory Medicine, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | - Anneke C Muller Kobold
- Department of Laboratory Medicine, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | - Bruce H R Wolffenbuttel
- Department of Endocrinology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | - André P van Beek
- Centre for Obesity Netherlands (CON), Medical Center Leeuwarden, Leeuwarden, The Netherlands; Department of Endocrinology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
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Abstract
Obesity prevalence continues to increase worldwide, as do the numerous chronic diseases associated with obesity, including diabetes, non-alcoholic fatty liver disease, dyslipidemia, and hypertension. The prevalence of bariatric surgery also continues to increase and remains the most effective and sustainable treatment for obesity. Over the last several years, numerous prospective and longitudinal studies have demonstrated the benefits of bariatric surgery on weight loss, mortality, and other chronic diseases. Even though the mechanisms underlying many of these beneficial effects remain poorly understood, surgical management of obesity continues to increase given its unmatched efficacy. In this commentary, we discuss recent clinical advancements as well as several areas needed for future research, including indications for bariatric and metabolic surgery, determination of responders and non-responders, metabolic surgery in non-obese individuals, and the evolving role of bariatric surgery in adolescents.
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Affiliation(s)
- Vance L Albaugh
- Department of Surgery, MCN CC-2308, Section of Surgical Sciences, Vanderbilt University Medical Center, Nashville, Tennessee, USA
| | - Naji N Abumrad
- Department of Surgery, MCN CC-2308, Section of Surgical Sciences, Vanderbilt University Medical Center, Nashville, Tennessee, USA
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47
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Affiliation(s)
- Kamal K Mahawar
- Bariatric Unit, Sunderland Royal Hospital, Sunderland, SR4 7TP, UK.
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48
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Holst JJ, Madsbad S, Bojsen-Møller KN, Svane MS, Jørgensen NB, Dirksen C, Martinussen C. Mechanisms in bariatric surgery: Gut hormones, diabetes resolution, and weight loss. Surg Obes Relat Dis 2018; 14:708-714. [PMID: 29776493 PMCID: PMC5974695 DOI: 10.1016/j.soard.2018.03.003] [Citation(s) in RCA: 141] [Impact Index Per Article: 20.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2018] [Accepted: 03/04/2018] [Indexed: 12/11/2022]
Abstract
Gastric bypass surgery leads to profound changes in the secretion of gut hormones with effects on metabolism, appetite, and food intake. Here, we discuss their contributions to the improvement in glucose tolerance and the weight loss that results from the operations. We find that the improved glucose tolerance is due the following events: a negative energy balance and resulting weight loss, which improve first hepatic and later peripheral insulin sensitivity, in combination with increased postprandial insulin secretion elicited particularly by exaggerated glucagon-like peptide-1 responses. The weight loss is due to loss of appetite resulting in reduced energy intake, and we find it probable that this process is driven by exaggerated secretion of appetite-regulating gut hormones including, but probably not limited to, glucagon-like peptide-1 and peptide-YY. The increased secretion is due to an accelerated exposure to and absorption of nutrients in the small intestine. This places the weight loss and the gut hormones in key positions with respect to the metabolic improvements after bypass surgery.
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Affiliation(s)
- Jens Juul Holst
- NNF Center for Basic Metabolic Research and Dept. Biomedical Sciences, the Panum Institute, University of Copenhagen, Copenhagen, Denmark.
| | - Sten Madsbad
- NNF Center for Basic Metabolic Research and Dept. Biomedical Sciences, the Panum Institute, University of Copenhagen, Copenhagen, Denmark; Department of Endocrinology, Hvidovre Hospital, University of Copenhagen, Copenhagen, Denmark
| | - Kirstine N Bojsen-Møller
- NNF Center for Basic Metabolic Research and Dept. Biomedical Sciences, the Panum Institute, University of Copenhagen, Copenhagen, Denmark; Department of Endocrinology, Hvidovre Hospital, University of Copenhagen, Copenhagen, Denmark
| | - Maria Saur Svane
- NNF Center for Basic Metabolic Research and Dept. Biomedical Sciences, the Panum Institute, University of Copenhagen, Copenhagen, Denmark; Department of Endocrinology, Hvidovre Hospital, University of Copenhagen, Copenhagen, Denmark
| | - Nils Bruun Jørgensen
- NNF Center for Basic Metabolic Research and Dept. Biomedical Sciences, the Panum Institute, University of Copenhagen, Copenhagen, Denmark; Department of Endocrinology, Hvidovre Hospital, University of Copenhagen, Copenhagen, Denmark
| | - Carsten Dirksen
- NNF Center for Basic Metabolic Research and Dept. Biomedical Sciences, the Panum Institute, University of Copenhagen, Copenhagen, Denmark; Department of Endocrinology, Hvidovre Hospital, University of Copenhagen, Copenhagen, Denmark
| | - Christoffer Martinussen
- NNF Center for Basic Metabolic Research and Dept. Biomedical Sciences, the Panum Institute, University of Copenhagen, Copenhagen, Denmark; Department of Endocrinology, Hvidovre Hospital, University of Copenhagen, Copenhagen, Denmark
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49
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Christensen BJ, Schmidt JB, Nielsen MS, Tækker L, Holm L, Lunn S, Bredie WLP, Ritz C, Holst JJ, Hansen T, Hilbert A, le Roux CW, Hulme OJ, Siebner H, Morville T, Naver L, Floyd AK, Sjödin A. Patient profiling for success after weight loss surgery (GO Bypass study): An interdisciplinary study protocol. Contemp Clin Trials Commun 2018; 10:121-130. [PMID: 30023446 PMCID: PMC6046467 DOI: 10.1016/j.conctc.2018.02.002] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2017] [Revised: 02/09/2018] [Accepted: 02/13/2018] [Indexed: 12/14/2022] Open
Abstract
Despite substantial research efforts, the mechanisms proposed to explain weight loss after gastric bypass (RYGB) and sleeve gastrectomy (SL) do not explain the large individual variation seen after these treatments. A complex set of factors are involved in the onset and development of obesity and these may also be relevant for the understanding of why success with treatments vary considerably between individuals. This calls for explanatory models that take into account not only biological determinants but also behavioral, affective and contextual factors. In this prospective study, we recruited 47 women and 8 men, aged 25–56 years old, with a BMI of 45.8 ± 7.1 kg/m2 from the waiting list for RYGB and SL at Køge hospital, Denmark. Pre-surgery and 1.5, 6 and 18 months after surgery we assessed various endpoints spanning multiple domains. Endpoints were selected on basis of previous studies and include: physiological measures: anthropometrics, vital signs, biochemical measures and appetite hormones, genetics, gut microbiota, appetite sensation, food and taste preferences, neural sensitivity, sensory perception and movement behaviors; psychological measures: general psychiatric symptom-load, depression, eating disorders, ADHD, personality disorder, impulsivity, emotion regulation, attachment pattern, general self-efficacy, alexithymia, internalization of weight bias, addiction, quality of life and trauma; and sociological and anthropological measures: sociodemographic measures, eating behavior, weight control practices and psycho-social factors. Joining these many endpoints and methodologies from different scientific disciplines and creating a multi-dimensional predictive model has not previously been attempted. Data on the primary endpoint are expected to be published in 2018. Trial registration Clinicaltrials. gov ID NCT02070081.
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Affiliation(s)
- Bodil Just Christensen
- Department of Food and Resource Economics, Faculty of Science, University of Copenhagen, Denmark
| | - Julie Berg Schmidt
- Department of Nutrition, Exercise and Sports, Faculty of Science, University of Copenhagen, Denmark
| | - Mette Søndergaard Nielsen
- Department of Nutrition, Exercise and Sports, Faculty of Science, University of Copenhagen, Denmark.,The Danish Diabetes Academy, Denmark
| | - Louise Tækker
- Department of Psychology, Faculty of Social Science, University of Copenhagen, Denmark
| | - Lotte Holm
- Department of Food and Resource Economics, Faculty of Science, University of Copenhagen, Denmark
| | - Susanne Lunn
- Department of Psychology, Faculty of Social Science, University of Copenhagen, Denmark
| | - Wender L P Bredie
- Department of Food Science, Faculty of Science, University of Copenhagen, Denmark
| | - Christian Ritz
- Department of Nutrition, Exercise and Sports, Faculty of Science, University of Copenhagen, Denmark
| | - Jens Juul Holst
- NNF Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark.,Department of Biomedical Sciences, University of Copenhagen, Denmark
| | - Torben Hansen
- NNF Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark
| | - Anja Hilbert
- Universitätsmedizin Leipzig, Integrated Research and Treatment Center Adiposity Diseases, Department of Medical Psychology and Medical Sociology, Germany
| | - Carel W le Roux
- Diabetes Complications Research Centre, Conway Institute, University College Dublin, Ireland
| | - Oliver J Hulme
- Danish Research Centre for Magnetic Resonance, Copenhagen University Hospital Hvidovre, Denmark
| | - Hartwig Siebner
- Danish Research Centre for Magnetic Resonance, Copenhagen University Hospital Hvidovre, Denmark.,Department of Neurology, Copenhagen University Hospital Bispebjerg, Copenhagen, Denmark
| | - Tobias Morville
- Danish Research Centre for Magnetic Resonance, Copenhagen University Hospital Hvidovre, Denmark
| | - Lars Naver
- Bariatric Clinic, Køge Hospital, Denmark
| | | | - Anders Sjödin
- Department of Nutrition, Exercise and Sports, Faculty of Science, University of Copenhagen, Denmark
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50
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Skogar M, Holmbäck U, Hedberg J, Risérus U, Sundbom M. Preserved Fat-Free Mass after Gastric Bypass and Duodenal Switch. Obes Surg 2018; 27:1735-1740. [PMID: 27885535 PMCID: PMC5489570 DOI: 10.1007/s11695-016-2476-6] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/11/2023]
Abstract
Background Concerns for the possibility of an excessive loss of fat-free mass (FFM) and resting metabolic rate (RMR) after bariatric surgery, such as Roux-en-Y gastric bypass (RYGB) and duodenal switch (BPD/DS), have been raised. Objectives This study aims to examine body composition and RMR in patients after RYGB and BPD/DS and in non-operated controls. Methods Body composition and RMR were studied with Bod Pod and indirect calorimetry in weight-stable RYGB (n = 15) and BPD/DS patients (n = 12) and compared with non-operated controls (n = 17). All patients were 30–55 years old and weight stable with BMI 28–35 kg/m2. Results FFM% was 58% (RYGB), 61% (BPD/DS), and 58% (controls). Body composition did not differ after RYGB and BPD/DS compared to controls, despite 27 and 40% total body weight loss, respectively. No difference in RMR or RMR/FFM was observed (1539, 1617, and 1490 kcal/24 h; and 28.9, 28.4, and 28.8 kcal/24 h/kg). Conclusion Weight-stable patients with BMI 28–35 kg/m2 after RYGB and BPD/DS have a body composition and RMR similar to that of non-operated individuals within the same BMI interval.
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Affiliation(s)
- Martin Skogar
- Department of Surgical Sciences, Uppsala University, SE-751 85, Uppsala, Sweden.
| | - Ulf Holmbäck
- Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism, Uppsala University, SE-751 85, Uppsala, Sweden
| | - Jakob Hedberg
- Department of Surgical Sciences, Uppsala University, SE-751 85, Uppsala, Sweden
| | - Ulf Risérus
- Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism, Uppsala University, SE-751 85, Uppsala, Sweden
| | - Magnus Sundbom
- Department of Surgical Sciences, Uppsala University, SE-751 85, Uppsala, Sweden
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