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Jung GH, Zahedi B, Bouxsein ML, Yu EW. Load-to-strength ratio as an estimate of wrist facture after gastric bypass vs gastric banding. JBMR Plus 2025; 9:ziae175. [PMID: 39906259 PMCID: PMC11791783 DOI: 10.1093/jbmrpl/ziae175] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/05/2024] [Revised: 12/20/2024] [Accepted: 12/27/2024] [Indexed: 02/06/2025] Open
Abstract
Bariatric surgeries such as Roux-en-Y gastric bypass (RYGB) and adjustable gastric banding (AGB) lead to long-term deficits in bone density but are also accompanied by decreased weight, which may lower the impact force with falls. The aim of this study was to compare the long-term skeletal impact of RYGB and AGB using a biomechanical evaluation of load-to-strength ratio at the distal radius as a surrogate for wrist fracture risk. We conducted a cross-sectional study evaluating bone microarchitectural parameters and bone turnover in adults who received either RYGB or AGB surgery ≥10 yr ago (RYGB: n = 22; AGB: n = 23). Bone strength at the distal radius was estimated by microfinite element analysis from HR-pQCT. We used a single-spring biomechanical model to estimate impact force and then calculated load-to-strength ratio as a ratio of impact force to bone strength, with higher load-to-strength ratios representing a higher susceptibility to fracture. In multivariable analyses, the RYGB group had higher bone resorption marker C-telopeptide (CTX) levels, lower volumetric bone density, and worse cortical and trabecular microarchitectural parameters than the AGB group. Furthermore, estimated bone strength at the radius was lower in the RYGB group (3725 ± 139 N vs 4141 ± 157 N, p = .030), and the load-to-strength ratio was higher in RYGB group as compared with AGB (0.84 ± 0.04 vs 0.72 ± 0.05, p = .035), suggestive of higher propensity for wrist fracture. Taken together, these results indicate the long-term deleterious skeletal effects are more concerning with RYGB than AGB.
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Affiliation(s)
- Grace H Jung
- Endocrine Unit, Department of Medicine, Massachusetts General Hospital, Boston, MA 02114, United States
| | - Bita Zahedi
- Endocrine Unit, Department of Medicine, Massachusetts General Hospital, Boston, MA 02114, United States
- Harvard Medical School, Boston, MA 02115, United States
| | - Mary L Bouxsein
- Endocrine Unit, Department of Medicine, Massachusetts General Hospital, Boston, MA 02114, United States
- Harvard Medical School, Boston, MA 02115, United States
- Department of Orthopedic Surgery, Beth Israel Deaconess Medical Center, Boston, MA 02115, United States
| | - Elaine W Yu
- Endocrine Unit, Department of Medicine, Massachusetts General Hospital, Boston, MA 02114, United States
- Harvard Medical School, Boston, MA 02115, United States
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Ardizzone A, Siracusa R, Capra AP, Di Paola R, Esposito E, Cuzzocrea S, D'Amico R, Impellizzeri D. Evaluating osteopontin as a biomarker of obesity related complications before and after metabolic and bariatric surgery: A systematic review and meta-analysis. Obes Res Clin Pract 2025; 19:19-27. [PMID: 39884900 DOI: 10.1016/j.orcp.2025.01.010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/31/2024] [Revised: 01/24/2025] [Accepted: 01/28/2025] [Indexed: 02/01/2025]
Abstract
BACKGROUND/OBJECTIVES Obesity is a major public health concern, significantly elevating the risk of developing comorbid conditions such as type 2 diabetes mellitus and cardio-vascular diseases, while also shortening life expectancy. Currently, metabolic and bariatric surgery (MBS) is one of the most effective long-term interventions for achieving substantial weight loss, alongside notable improvements in overall quality of life. However, evidence suggests that these procedures may negatively affect bone health, leading to an increased risk of fractures. This systematic review and meta-analysis aim to assess the role of Osteopontin (OPN) as a potential biomarker for predicting both persistent inflammation and bone deterioration following MBS. METHODS A comprehensive search of scientific databases including PubMed (MEDLINE), Embase (OVID), and Web of Science, covering literature up to January 31, 2024, identified 6 studies that met the inclusion criteria for the systematic review. For the meta-analysis, data from 5 studies measuring circulating OPN levels pre- and post-surgery were pooled. RESULTS The combined analysis revealed a significant increase in OPN levels after MBS compared to baseline (OR: 24.56; 95 % CI: 13.30-35.81; p < 0.0001). CONCLUSIONS These findings suggest that OPN may serve as a valuable biomarker for monitoring inflammation and assessing the risk of bone-related complications in patients following MBS.
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Affiliation(s)
- Alessio Ardizzone
- Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Viale Ferdinando Stagno D'Alcontres, 31, Messina 98166, Italy.
| | - Rosalba Siracusa
- Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Viale Ferdinando Stagno D'Alcontres, 31, Messina 98166, Italy.
| | - Anna Paola Capra
- Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Viale Ferdinando Stagno D'Alcontres, 31, Messina 98166, Italy.
| | - Rosanna Di Paola
- Department of Veterinary Science, University of Messina, Messina 98168, Italy.
| | - Emanuela Esposito
- Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Viale Ferdinando Stagno D'Alcontres, 31, Messina 98166, Italy.
| | - Salvatore Cuzzocrea
- Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Viale Ferdinando Stagno D'Alcontres, 31, Messina 98166, Italy; Link Campus University, Via del Casale di San Pio V 44, Roma, Italy.
| | - Ramona D'Amico
- Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Viale Ferdinando Stagno D'Alcontres, 31, Messina 98166, Italy.
| | - Daniela Impellizzeri
- Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Viale Ferdinando Stagno D'Alcontres, 31, Messina 98166, Italy.
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Vachliotis ID, Anastasilakis AD, Rafailidis V, Polyzos SA. Osteokines in Nonalcoholic Fatty Liver Disease. Curr Obes Rep 2024; 13:703-723. [PMID: 39225951 DOI: 10.1007/s13679-024-00586-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 08/21/2024] [Indexed: 09/04/2024]
Abstract
PURPOSE OF REVIEW To critically summarize evidence on the potential role of osteokines in the pathogenesis and progression of nonalcoholic fatty liver disease (NAFLD). RECENT FINDINGS There are emerging data supporting that certain osteokines, which are specific bone-derived proteins, may beneficially or adversely affect hepatic metabolism, and their alterations in the setting of osteoporosis or other bone metabolic diseases may possibly contribute to the development and progression of NAFLD. There is evidence showing a potential bidirectional association between NAFLD and bone metabolism, which may imply the existence of a liver-bone axis. In this regard, osteocalcin, osteoprotegerin, bone morphogenic protein 4 (BMP4) and BMP6 appear to have a positive impact on the liver, thus possibly alleviating NAFLD, whereas osteopontin, receptor activator of nuclear factor kappa Β ligand (RANKL), sclerostin, periostin, BMP8B, and fibroblast growth factor 23 (FGF23) appear to have a negative impact on the liver, thus possibly exacerbating NAFLD. The potential implication of osteokines in NAFLD warrants further animal and clinical research in the field that may possibly result in novel therapeutic targets for NAFLD in the future.
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Affiliation(s)
- Ilias D Vachliotis
- First Laboratory of Pharmacology, School of Medicine, Aristotle University of Thessaloniki, 54124, Thessaloniki, Greece.
| | | | - Vasileios Rafailidis
- Department of Clinical Radiology, AHEPA University Hospital of Thessaloniki, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Stergios A Polyzos
- First Laboratory of Pharmacology, School of Medicine, Aristotle University of Thessaloniki, 54124, Thessaloniki, Greece.
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Moriero M, Verzola D, Bertolotto M, Minetti S, Contini P, Ramoni D, Liberale L, Pontremoli R, Viazzi F, Pende A, Pisciotta L, Montecucco F, Carbone F. Baseline urinary osteopontin levels are associated with the improvement of metabolic syndrome. Nutr Metab Cardiovasc Dis 2024; 34:1874-1878. [PMID: 38664124 DOI: 10.1016/j.numecd.2024.03.028] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/05/2024] [Revised: 03/19/2024] [Accepted: 03/26/2024] [Indexed: 07/13/2024]
Abstract
BACKGROUND AND AIMS While serum osteopontin (OPN)'s established role in cardiometabolic risk is recognized, its potential as a predictor of metabolic syndrome (MetS) improvement through a urine assay has not yet been demonstrated. In this study, we propose its potential predictive role over a 12-month period of standard care, with the ability to complement anthropometric measures. METHODS AND RESULTS Hierarchical clustering revealed a notable association of urinary OPN (uOPN) with MetS criteria and overcame anthropometric measures in predicting the improvement at 12 months (OR of 2.74 [95% CI 1.32 to 6.29]). uOPN significantly contributed to the homogeneity of the nodes in the random forest and ultimately enhanced the performance of anthropometric measures when assessed for accuracy and area under the curve (AUC). CONCLUSION Our findings offer insights into potential applications in cardiometabolic medicine for uOPN, which is easily detectable in non-invasive biological samples through an affordable assay.
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Affiliation(s)
- Margherita Moriero
- First Clinic of Internal Medicine, Department of Internal Medicine, University of Genoa, Genoa, Italy
| | - Daniela Verzola
- First Clinic of Internal Medicine, Department of Internal Medicine, University of Genoa, Genoa, Italy
| | - Maria Bertolotto
- First Clinic of Internal Medicine, Department of Internal Medicine, University of Genoa, Genoa, Italy
| | - Silvia Minetti
- First Clinic of Internal Medicine, Department of Internal Medicine, University of Genoa, Genoa, Italy
| | - Paola Contini
- First Clinic of Internal Medicine, Department of Internal Medicine, University of Genoa, Genoa, Italy
| | - Davide Ramoni
- First Clinic of Internal Medicine, Department of Internal Medicine, University of Genoa, Genoa, Italy
| | - Luca Liberale
- First Clinic of Internal Medicine, Department of Internal Medicine, University of Genoa, Genoa, Italy; IRCCS Ospedale Policlinico San Martino, Genoa - Italian Cardiovascular Network, Genoa, Italy
| | - Roberto Pontremoli
- First Clinic of Internal Medicine, Department of Internal Medicine, University of Genoa, Genoa, Italy; IRCCS Ospedale Policlinico San Martino, Genoa, Genoa, Italy
| | - Francesca Viazzi
- First Clinic of Internal Medicine, Department of Internal Medicine, University of Genoa, Genoa, Italy; IRCCS Ospedale Policlinico San Martino, Genoa, Genoa, Italy
| | - Aldo Pende
- First Clinic of Internal Medicine, Department of Internal Medicine, University of Genoa, Genoa, Italy; IRCCS Ospedale Policlinico San Martino, Genoa, Genoa, Italy
| | - Livia Pisciotta
- First Clinic of Internal Medicine, Department of Internal Medicine, University of Genoa, Genoa, Italy; IRCCS Ospedale Policlinico San Martino, Genoa, Genoa, Italy
| | - Fabrizio Montecucco
- First Clinic of Internal Medicine, Department of Internal Medicine, University of Genoa, Genoa, Italy; IRCCS Ospedale Policlinico San Martino, Genoa - Italian Cardiovascular Network, Genoa, Italy
| | - Federico Carbone
- First Clinic of Internal Medicine, Department of Internal Medicine, University of Genoa, Genoa, Italy; IRCCS Ospedale Policlinico San Martino, Genoa - Italian Cardiovascular Network, Genoa, Italy.
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Gala K, Ghusn W, Abu Dayyeh BK. Gut motility and hormone changes after bariatric procedures. Curr Opin Endocrinol Diabetes Obes 2024; 31:131-137. [PMID: 38533785 DOI: 10.1097/med.0000000000000860] [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] [Indexed: 03/28/2024]
Abstract
PURPOSE OF REVIEW Metabolic and bariatric surgery (MBS) and endoscopic bariatric therapies (EBT) are being increasingly utilized for the management of obesity. They work through multiple mechanisms, including restriction, malabsorption, and changes in the gastrointestinal hormonal and motility. RECENT FINDINGS Roux-en-Y gastric bypass (RYGB) and laparoscopic sleeve gastrectomy (LSG) cause decrease in leptin, increase in GLP-1 and PYY, and variable changes in ghrelin (generally thought to decrease). RYGB and LSG lead to rapid gastric emptying, increase in small bowel motility, and possible decrease in colonic motility. Endoscopic sleeve gastroplasty (ESG) causes decrease in leptin and increase in GLP-1, ghrelin, and PYY; and delayed gastric motility. SUMMARY Understanding mechanisms of action for MBS and EBT is critical for optimal care of patients and will help in further refinement of these interventions.
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Affiliation(s)
- Khushboo Gala
- Department of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
| | - Wissam Ghusn
- Department of Internal Medicine, Boston University Medical Center, Boston, Massachusetts, USA
| | - Barham K Abu Dayyeh
- Department of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
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Öztürk D, Koca AO, Keskin M, Öztürk B, Oğuz EF, Turhan T, Buluş H. Patients who received sleeve gastrectomy have lower plasma osteopontin levels than those who did not. Clinics (Sao Paulo) 2024; 79:100352. [PMID: 38574573 PMCID: PMC10999792 DOI: 10.1016/j.clinsp.2024.100352] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/14/2023] [Accepted: 03/03/2024] [Indexed: 04/06/2024] Open
Abstract
BACKGROUND The aim of this study was to compare metabolic parameters, plasma Osteopontin (OPN) and Hepatocyte Growth Factor (HGF) levels between Sleeve Gastrectomy (SG) patients in their 6th post-operation month and healthy control patients. METHODS Height, weight, Body Mass Index (BMI) and laboratory parameters of 58 SG patients aged 18‒65 years (Group 1) and 46 healthy control patients (Group 2) were compared. In addition, preoperative and postoperative sixth-month BMI and laboratory parameters of the patients in Group 1 were compared. RESULTS The mean age and gender distributions of the groups were similar (p > 0.05). Mean BMI was 28.9 kg/m2 in Group 1 and 27 kg/m2 in Group 2 (p < 0.01). While plasma HGF levels were similar between both groups, plasma OPN levels were higher in Group 2 (p < 0.001). Fasting plasma glucose, total cholesterol, triglyceride, fasting plasma insulin and insulin resistance values were higher in Group 1, while alanine aminotransferase and aspartate aminotransferase levels were higher in Group 2 (p < 0.05). There was a strong correlation between plasma HGF and OPN levels in Group 1, but not in Group 2 (Rho = 0.805, p < 0.001). CONCLUSION OPN and HGF are promising biomarkers that can be used to better understand and detect problems related to obesity. The fact that patients in the early post-SG period had lower plasma OPN and similar plasma HGF compared to non-surgical patients of similar age and gender with higher BMI may be another favorable and previously unknown metabolic effect of SG.
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Affiliation(s)
- Doğan Öztürk
- University of Health Sciences, Ankara Atatürk Sanatoryum Education and Research Hospital, Department of General Surgery, Ankara, Turkey.
| | - Arzu Or Koca
- University of Health Sciences, Dr. Abdurrahman Yurtaslan Ankara Onkoloji Education and Research Hospital, Department of Endocrinology and Metabolism, Ankara, Turkey
| | - Müge Keskin
- University of Health Sciences, Ankara City Hospital, Department of Endocrinology and Metabolism, Ankara, Turkey
| | - Bülent Öztürk
- University of Health Sciences, Ankara Atatürk Sanatoryum Education and Research Hospital, Department of General Surgery, Ankara, Turkey
| | - Esra Fırat Oğuz
- University of Health Sciences, Ankara City Hospital, Department of Medical Biochemistry, Ankara, Turkey
| | - Turan Turhan
- University of Health Sciences, Ankara City Hospital, Department of Medical Biochemistry, Ankara, Turkey
| | - Hakan Buluş
- University of Health Sciences, Ankara Atatürk Sanatoryum Education and Research Hospital, Department of General Surgery, Ankara, Turkey
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Yin M, Wang Y, Han M, Liang R, Li S, Wang G, Gang X. Mechanisms of bariatric surgery for weight loss and diabetes remission. J Diabetes 2023; 15:736-752. [PMID: 37442561 PMCID: PMC10509523 DOI: 10.1111/1753-0407.13443] [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: 02/22/2023] [Revised: 06/12/2023] [Accepted: 06/26/2023] [Indexed: 07/15/2023] Open
Abstract
Obesity and type 2 diabetes(T2D) lead to defects in intestinal hormones secretion, abnormalities in the composition of bile acids (BAs), increased systemic and adipose tissue inflammation, defects of branched-chain amino acids (BCAAs) catabolism, and dysbiosis of gut microbiota. Bariatric surgery (BS) has been shown to be highly effective in the treatment of obesity and T2D, which allows us to view BS not simply as weight-loss surgery but as a means of alleviating obesity and its comorbidities, especially T2D. In recent years, accumulating studies have focused on the mechanisms of BS to find out which metabolic parameters are affected by BS through which pathways, such as which hormones and inflammatory processes are altered. The literatures are saturated with the role of intestinal hormones and the gut-brain axis formed by their interaction with neural networks in the remission of obesity and T2D following BS. In addition, BAs, gut microbiota and other factors are also involved in these benefits after BS. The interaction of these factors makes the mechanisms of metabolic improvement induced by BS more complicated. To date, we do not fully understand the exact mechanisms of the metabolic alterations induced by BS and its impact on the disease process of T2D itself. This review summarizes the changes of intestinal hormones, BAs, BCAAs, gut microbiota, signaling proteins, growth differentiation factor 15, exosomes, adipose tissue, brain function, and food preferences after BS, so as to fully understand the actual working mechanisms of BS and provide nonsurgical therapeutic strategies for obesity and T2D.
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Affiliation(s)
- Mengsha Yin
- Department of Endocrinology and MetabolismThe First Hospital of Jilin UniversityChangchunChina
| | - Yao Wang
- Department of OrthopedicsThe Second Hospital Jilin UniversityChangchunChina
| | - Mingyue Han
- Department of Endocrinology and MetabolismThe First Hospital of Jilin UniversityChangchunChina
| | - Ruishuang Liang
- Department of Endocrinology and MetabolismThe First Hospital of Jilin UniversityChangchunChina
| | - Shanshan Li
- Department of Endocrinology and MetabolismThe First Hospital of Jilin UniversityChangchunChina
| | - Guixia Wang
- Department of Endocrinology and MetabolismThe First Hospital of Jilin UniversityChangchunChina
| | - Xiaokun Gang
- Department of Endocrinology and MetabolismThe First Hospital of Jilin UniversityChangchunChina
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Cicekli I, Saglam D, Takar N. A New Perspective on Metabolic Syndrome with Osteopontin: A Comprehensive Review. Life (Basel) 2023; 13:1608. [PMID: 37511983 PMCID: PMC10381599 DOI: 10.3390/life13071608] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2023] [Revised: 06/12/2023] [Accepted: 07/18/2023] [Indexed: 07/30/2023] Open
Abstract
Metabolic syndrome (MetS) imposes a substantial burden on the healthcare systems and economies of countries and is a major public health concern worldwide. MetS is mainly caused by an imbalance between calorie intake and energy expenditure; however, it is recognized that additional variables, such as chronic inflammation, may have the same predictive potential as insulin resistance or MetS components in the genesis of type 2 diabetes and cardiovascular events. More importantly, the early diagnosis or treatment of MetS may significantly reduce the burden on the health systems of the disease with any prevention or biomarker and should not be underestimated. Osteopontin (OPN), also called secreted phosphoprotein 1, is a soluble protein found mostly in body fluids. Studies suggest that serum OPN levels may be an early and new biomarker to predict metabolic and cardiovascular complications significantly associated with some diseases. This review aims to provide specific insight into the new biomarker OPN in MetS. With this purpose, it is examined the link between the MetS cornerstones and OPN. In addition, the interaction between the microbiota and MetS is predicted to be bidirectional, and the microbiota may act as a bridge in this interaction process. Increased OPN levels may have unfavourable consequences for cardiovascular diseases, diabetes, and obesity, all of which are components of MetS. Further studies are required to evaluate the use of OPN levels as a clinical biomarker risk of MetS.
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Affiliation(s)
- Ipek Cicekli
- Department of Nutrition and Dietetics, Faculty of Health Sciences, Acibadem Mehmet Ali Aydinlar University, Istanbul 34752, Turkey
| | - Duygu Saglam
- Department of Nutrition and Dietetics, Faculty of Health Sciences, Acibadem Mehmet Ali Aydinlar University, Istanbul 34752, Turkey
| | - Nadir Takar
- Department of Family Medicine, Kartal Dr. Lutfi Kirdar City Hospital, Istanbul Provincial Directorate of Health, Istanbul 34865, Turkey
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Huang J, Chen Y, Wang X, Wang C, Yang J, Guan B. Change in Adipokines and Gastrointestinal Hormones After Bariatric Surgery: a Meta-analysis. Obes Surg 2023; 33:789-806. [PMID: 36607567 DOI: 10.1007/s11695-022-06444-8] [Citation(s) in RCA: 18] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2022] [Revised: 12/21/2022] [Accepted: 12/27/2022] [Indexed: 01/07/2023]
Abstract
PURPOSE The study aimed to perform a meta-analysis about the change in adipokines and gastrointestinal hormones after bariatric surgery in patients with obesity. MATERIALS AND METHODS We searched the Cochrane Central Register of Controlled Trials, EMBASE, and PubMed for related articles and used Review Manager 5.4 for data aggregation. Sensitivity and subgroup analysis were also conducted when feasible. RESULTS As a result, 95 articles involving 6232 patients were included in the meta-analysis. After bariatric surgery, the levels of leptin, ghrelin, C-reactive protein (CRP), interleukin-6 (IL-6), high-sensitivity C-reactive protein (Hs-CRP), tumor necrosis, factor-α (TNF-α), and interleukin-1β (IL-1β) reduced, while adiponectin, glucagon-like peptide-1 (GLP-1), and peptide YY (PYY) levels increased significantly. Subgroup analysis indicated that there was a more significant reduction in leptin level with a longer follow-up time. OAGB had a greater effect on increasing adiponectin level compared with other procedures. SG procedure would bring about reduced ghrelin, while BPD resulted in increased ghrelin. Meta-regression analysis found that publication year, study design, number of patients, preoperative age, preoperative BMI, and quality assessment score were not significantly related to change in leptin, adiponectin, and ghrelin levels. CONCLUSION Bariatric surgery was associated with a significant decrease in leptin, ghrelin, CRP, IL-6, Hs-CRP, TNF-α, and IL-1β, as well as increase in adiponectin, GLP-1, and PYY levels.
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Affiliation(s)
- Jiayun Huang
- School of Nursing, Jinan University, Guangzhou, 510632, China
| | - Yanya Chen
- School of Nursing, Jinan University, Guangzhou, 510632, China
- Department of Infectious Diseases and Public Health, Jockey Club College of Veterinary Medicine and Life Sciences, City University of Hong Kong, Hong Kong, 999077, China
| | - Xuan Wang
- School of Nursing, Jinan University, Guangzhou, 510632, China
| | - Cunchuan Wang
- Department of Gastrointestinal Surgery, First Affiliated Hospital of Jinan University, Guangzhou, 510632, China
| | - Jingge Yang
- Department of Gastrointestinal Surgery, First Affiliated Hospital of Jinan University, Guangzhou, 510632, China.
| | - Bingsheng Guan
- Department of Gastrointestinal Surgery, First Affiliated Hospital of Jinan University, Guangzhou, 510632, China.
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10
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Felipe LA, Bachi ALL, Oliveira MC, Moreira SMBP, Afonso JPR, Lino MEM, Paixão V, Silva CHM, Vieira RP, Vencio S, Jirjos EI, Malheiros CA, Insalaco G, Júnior WRF, Oliveira LVF. Effects of Roux-en-Y gastric bypass on the metabolic profile and systemic inflammatory status of women with metabolic syndrome: randomized controlled clinical trial. Diabetol Metab Syndr 2023; 15:19. [PMID: 36788619 PMCID: PMC9930348 DOI: 10.1186/s13098-023-00986-2] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/06/2022] [Accepted: 01/25/2023] [Indexed: 02/16/2023] Open
Abstract
BACKGROUND Obesity remains a public health problem worldwide. The high prevalence of this condition in the population raises further concerns, considering that comorbidities are often associated with obesity. Among the comorbidities closely associated with obesity, metabolic syndrome (MS) is particularly important, which potentially increases the risk of manifestation of other disorders, such as the prothrombotic and systemic pro-inflammatory states. METHODS A randomized, controlled clinical trial was performed involving female patients (n = 32) aged between 18 and 65 years, with a clinical diagnosis of MS, with severe obesity undergoing Roux-en-Y gastric bypass (RYGB). The study design followed the Consolidated Standards of Reporting Trials statement (CONSORT). Lipid profile, blood glucose and adipokines (adiponectin, leptin, and resistin) and (cytokines IL-1β, IL-6, IL-17, IL-23, and TNF-α) in blood plasma samples were evaluated before and six months after RYGB. RESULTS Patients undergoing RYGB (BSG) showed a significant improvement from preoperative grade III obesity to postoperative grade I obesity. The results showed that while HDL levels increased, the other parameters showed a significant reduction in their postoperative values when compared not only to the values observed before surgery in the BSG group, but also to the values obtained in the control group (CG). As for systemic inflammatory markers adiponectin, leptin, resistin, IL-1β, IL-6, IL-17, IL-23 and TNF- α it was observed that the levels of resistin and IL-17 in the second evaluation increased significantly when compared to the levels observed in the first evaluation in the CG. In the BSG group, while the levels of adiponectin increased, the levels of the other markers showed significant reductions in the postoperative period, in relation to the respective preoperative levels. The analysis of Spearman's correlation coefficient showed a significant positive correlation between IL-17 and IL-23 in the preoperative period, significant positive correlations between TNF-α and IL-6, TNF-α and IL-17, IL-6 and IL-17, and IL-17 and IL-23 were observed postoperatively. CONCLUSIONS According to our results, the reduction of anthropometric measurements induced by RYGB, significantly improves not only the plasma biochemical parameters (lipid profile and glycemia), but also the systemic inflammatory status of severely obese patients with MS. Trials registration NCT02409160.
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Affiliation(s)
- Lucenda A Felipe
- Post-Graduation Program in Health Sciences, Santa Casa of Sao Paulo Medical School, Sao Paulo, SP, 01221-010, Brazil
| | - André L L Bachi
- Post-Graduation Program in Health Sciences, Santo Amaro University (UNISA), São Paulo, SP, Brazil
| | - Miriã C Oliveira
- Human Movement and Rehabilitation Post Graduation Program, Evangelical University of Goiás (UniEVANGELICA), Anápolis, GO, Brazil
| | - Sandra M B P Moreira
- Post-Graduation Program in Health Sciences, Santa Casa of Sao Paulo Medical School, Sao Paulo, SP, 01221-010, Brazil
| | - João Pedro R Afonso
- Human Movement and Rehabilitation Post Graduation Program, Evangelical University of Goiás (UniEVANGELICA), Anápolis, GO, Brazil
| | - Maria E M Lino
- Scientific Initiation Program, Evangelical University of Goiás, (UniEVANGELICA), Anápolis, GO, Brazil
| | - Vitória Paixão
- Department of Otorhinolaryngology, ENT Lab, Federal University of São Paulo (UNIFESP), São Paulo, SP, 04021-001, Brazil
| | - Carlos H M Silva
- Human Movement and Rehabilitation Post Graduation Program, Evangelical University of Goiás (UniEVANGELICA), Anápolis, GO, Brazil
| | - Rodolfo P Vieira
- Human Movement and Rehabilitation Post Graduation Program, Evangelical University of Goiás (UniEVANGELICA), Anápolis, GO, Brazil
| | - Sergio Vencio
- Institute of Pharmaceutical Sciences, Goiania, (GO), Brazil
| | - Elias I Jirjos
- Post-Graduation Program in Health Sciences, Santa Casa of Sao Paulo Medical School, Sao Paulo, SP, 01221-010, Brazil
| | - Carlos A Malheiros
- Post-Graduation Program in Health Sciences, Santa Casa of Sao Paulo Medical School, Sao Paulo, SP, 01221-010, Brazil
| | - Giuseppe Insalaco
- Institute for Biomedical Research and Innovation, National Research Council of Italy (CNR), 90146, Palermo, Italy
| | - Wilson R Freitas Júnior
- Post-Graduation Program in Health Sciences, Santa Casa of Sao Paulo Medical School, Sao Paulo, SP, 01221-010, Brazil
| | - Luis V F Oliveira
- Human Movement and Rehabilitation Post Graduation Program, Evangelical University of Goiás (UniEVANGELICA), Anápolis, GO, Brazil.
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Snelder SM, Pouw N, Aga Y, Castro Cabezas M, Biter LU, Zijlstra F, Kardys I, van Dalen BM. Cardiovascular Biomarker Profiles in Obesity and Relation to Normalization of Subclinical Cardiac Dysfunction after Bariatric Surgery. Cells 2022; 11:cells11030422. [PMID: 35159232 PMCID: PMC8834585 DOI: 10.3390/cells11030422] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2021] [Revised: 01/18/2022] [Accepted: 01/20/2022] [Indexed: 12/13/2022] Open
Abstract
Aims: We aimed to gain insight into the underlying pathophysiology of cardiac dysfunction in obesity patients and the improvement of cardiac function after weight loss. Methods: This is a longitudinal study in which 92 cardiovascular biomarkers were measured by multiplex immunoassays in obesity patients without known cardiovascular disease, before and one year after bariatric surgery. Results: Out of 100 eligible patients, 72 patients completed the follow-up. A total of 72 (78%) biomarkers changed significantly. The biomarkers with the highest relative changes represented processes linked mainly to insulin resistance and inflammation. In the patients with persistent subclinical cardiac dysfunction, the baseline values of 10 biomarkers were different from values in patients with normalization of cardiac function. Most of these biomarkers were linked to inflammation or atherosclerosis. Finally, a model was developed to investigate the relationship between changes in the biomarkers and persistent subclinical cardiac dysfunction. Seven biomarkers were retained in this model, mainly linked to inflammation, atherosclerosis, and hypercoagulability. Conclusion: The majority (78%) of cardiovascular biomarkers changed, pointing mainly to modulation of insulin resistance and inflammation. The baseline levels of 10 biomarkers, as well as pre- to post-bariatric surgery changes in seven biomarkers, were related to persistent subclinical cardiac dysfunction after bariatric surgery.
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Affiliation(s)
- Sanne M. Snelder
- Department of Cardiology, Franciscus Gasthuis & Vlietland, 3045 PM Rotterdam, The Netherlands; (S.M.S.); (Y.A.)
| | - Nadine Pouw
- Department of Clinical Chemistry, Franciscus Gasthuis & Vlietland, 3045 PM Rotterdam, The Netherlands;
| | - Yaar Aga
- Department of Cardiology, Franciscus Gasthuis & Vlietland, 3045 PM Rotterdam, The Netherlands; (S.M.S.); (Y.A.)
| | - Manuel Castro Cabezas
- Department of Internal Medicine, Franciscus Gasthuis & Vlietland, 3045 PM Rotterdam, The Netherlands;
| | - L. Ulas Biter
- Department of Surgery, Franciscus Gasthuis & Vlietland, 3045 PM Rotterdam, The Netherlands;
| | - Felix Zijlstra
- Department of Cardiology, Thoraxcenter, Erasmus University Medical Center Rotterdam, Erasmus MC, 3015 GD Rotterdam, The Netherlands; (F.Z.); (I.K.)
| | - Isabella Kardys
- Department of Cardiology, Thoraxcenter, Erasmus University Medical Center Rotterdam, Erasmus MC, 3015 GD Rotterdam, The Netherlands; (F.Z.); (I.K.)
| | - Bas M. van Dalen
- Department of Cardiology, Franciscus Gasthuis & Vlietland, 3045 PM Rotterdam, The Netherlands; (S.M.S.); (Y.A.)
- Department of Cardiology, Thoraxcenter, Erasmus University Medical Center Rotterdam, Erasmus MC, 3015 GD Rotterdam, The Netherlands; (F.Z.); (I.K.)
- Correspondence: ; Tel.: +31-10-4616139
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12
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Al-Rawaf HA, Alghadir AH, Gabr SA. Expression of Circulating MicroRNAs and Myokines and Interactions with Serum Osteopontin in Type 2 Diabetic Patients with Moderate and Poor Glycemic Control: A Biochemical and Molecular Study. BIOMED RESEARCH INTERNATIONAL 2021; 2021:7453000. [PMID: 34917685 PMCID: PMC8670937 DOI: 10.1155/2021/7453000] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/16/2021] [Accepted: 11/15/2021] [Indexed: 11/18/2022]
Abstract
BACKGROUND Cellular miRNAs are expressed in tissue fluids with sufficient amounts and were identified as potential molecular targets for studying the physiological mechanisms and correlations with many human diseases particularly diabetes. However, molecular-based changes among older adults with diabetes mellitus (DM) are rarely fully elucidated. AIM This study is aimed at identifying circulating miRNAs, which hold the potential to serve as biomarkers for the immune-inflammatory changes in older T2D patients with moderate and poor glycemic control status. In addition, the association of both myokines and osteopontin (OPN) levels with circulating miRNAs was identified. METHODS A total of 80 subjects aged 20-80 years were invited during the period of October 2017-May 2018 to participate in this descriptive cross-sectional study. All subjects were diagnosed with T2D for more than 5 years. Subjects were grouped based on glycemic control (HbA1c values) into two groups: moderate glycemic control (>7-8% HbA1c, no = 30) and poor glycemic control (>8% HbA1c, no = 50), respectively. Diabetic control parameters, fasting blood sugar (FS), HbA1c, fasting insulin (IF), insulin resistance (IR), HOMA-IR, inflammatory cytokines (IL-6, IL-8, IL-18, IL-23, TNF-α, and CRP), osteopontin, and myokines (adropin and irisin) were estimated by colorimetric and immune ELISA assays, respectively. In addition, real-time RT-PCR analysis was performed to evaluate the expression of circulating miRNAs, miR-146a and miR-144, in the serum of all diabetic subjects. RESULTS In this study, T2D patients with poor glycemic control showed a significant increase in the serum levels of IL-6, IL-8, IL-18, IL-23, TNF-α, CRP, and OPN and a reduction in the levels of myokines, adropin and irisin, compared to patients with moderate glycemic control. The results obtained are significantly correlated with the severity of diabetes measured by HbA1c, FS, IF, and HOMA-IR. In addition, baseline expression of miR-146a is significantly reduced and miR-144 is significantly increased in T2D patients with poor glycemic control compared to those with moderate glycemic control. In all diabetic groups, the expression of miR-146a and miR-144 is significantly correlated with diabetic controls, inflammatory cytokines, myokines, and serum levels of OPN. Respective of gender, women with T2D showed more significant change in the expressed miRNAs, inflammatory cytokines, OPN, and serum myokine markers compared to men. ROC analysis identified AUC cutoff values of miR-146a, miR-144, adropin, irisin, and OPN expression levels with considerable specificity and sensitivity which recommends the potential use of adropin, irisin, and OPN as diagnostic biomarkers for diabetes with varying glycemic control status. CONCLUSION In this study, molecular expression of certain microRNA species, such as miR-146a and miR-144, was identified and significantly associated with parameters of disease severity, HbA1c, inflammatory cytokines, myokines, and serum osteopontin in T2D patients with moderate and poor glycemic control. The AUC cutoff values of circulating miRNAs, miR-146a and miR-144; myokines, adropin and irisin; and serum OPN were significantly identified by ROC analysis which additionally recommends the potential use of these biomarkers, miR-146a, miR-144, adropin, irisin, and OPN, as diagnostic biomarkers with considerable specificity and sensitivity for diabetes in patients with varying glycemic control status.
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Affiliation(s)
- Hadeel A. Al-Rawaf
- Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Saud University, P.O. Box 10219, Riyadh 11433, Saudi Arabia
| | - Ahmad H. Alghadir
- Department of Rehabilitation Sciences, College of Applied Medical Sciences, King Saud University, P.O. Box 10219, Riyadh 11433, Saudi Arabia
| | - Sami A. Gabr
- Department of Rehabilitation Sciences, College of Applied Medical Sciences, King Saud University, P.O. Box 10219, Riyadh 11433, Saudi Arabia
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Caserza L, Casula M, Elia E, Bonaventura A, Liberale L, Bertolotto M, Artom N, Minetti S, Contini P, Verzola D, Pontremoli R, Viazzi F, Viviani GL, Bertolini S, Pende A, Pisciotta L, Montecucco F, Carbone F. Serum osteopontin predicts glycaemic profile improvement in metabolic syndrome: A pilot study. Eur J Clin Invest 2021; 51:e13403. [PMID: 32918277 DOI: 10.1111/eci.13403] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/03/2020] [Revised: 08/06/2020] [Accepted: 08/15/2020] [Indexed: 12/27/2022]
Abstract
Prediabetes is often observed in patients with Metabolic Syndrome (MetS) and might be associated with metabolic and inflammatory alterations. Here, we investigated whether the inflammatory molecule osteopontin (OPN) might have a prognostic impact in a cohort of MetS patients (n = 85) with baseline normal glycaemia or impaired fasting glucose (IFG) over one year of recommended pharmacological treatments and Mediterranean diet. Patients were then followed up for 12 months with intermediate evaluation after 6 months. At all time points, anthropometric and clinical data were recorded, alongside with haematological and biochemical profiles, including serum concentrations of OPN. As expected, Mediterranean diet improves glycaemic profile in patients with IFG. Baseline serum OPN failed to be associated with baseline anthropometric or biochemical variables. At baseline, higher levels of OPN were shown in patients with IFG as compared to normal glycaemia. Two distinct subgroups of patients in whom OPN decreased or remained stable/increased at follow-up were identified. When higher serum OPN levels were observed at baseline, greater reduction was observed at 1-year follow-up. Reduction in circulating OPN levels was associated with metabolic improvement in terms of blood pressure, LDL-c, HDL-c, and glycaemia. At both univariate and adjusted logistic regression analyses, serum OPN emerged as an independent predictor of glycaemic profile improvement at 1-year follow-up (adjOR 1.05 [1.00-1.10]; P = .041). In conclusion, pharmacological and dietetic interventions improved glycaemic profile in patients with MetS. In particular, glycaemic improvement was demonstrated in patients who also reduce circulating OPN levels. Higher OPN levels at baseline predict normalization of glycaemic profile.
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Affiliation(s)
- Lara Caserza
- First Clinic of Internal Medicine, Department of Internal Medicine, University of Genoa, Genoa, Italy
| | - Matteo Casula
- Division of Cardiology, Department of Internal Medicine, Turin, Italy
| | - Edorado Elia
- Division of Cardiology, Department of Internal Medicine, Turin, Italy
| | - Aldo Bonaventura
- First Clinic of Internal Medicine, Department of Internal Medicine, University of Genoa, Genoa, Italy
- Department of Internal Medicine, Division of Cardiology, Pauley Heart Center, Virginia Commonwealth University, Richmond, VA, USA
| | - Luca Liberale
- First Clinic of Internal Medicine, Department of Internal Medicine, University of Genoa, Genoa, Italy
- Center for Molecular Cardiology, University of Zürich, Switzerland
| | - Maria Bertolotto
- First Clinic of Internal Medicine, Department of Internal Medicine, University of Genoa, Genoa, Italy
| | - Nathan Artom
- Department of Internal Medicine, Ospedale S. Paolo di Savona, Savona, Italy
| | - Silvia Minetti
- First Clinic of Internal Medicine, Department of Internal Medicine, University of Genoa, Genoa, Italy
| | - Paola Contini
- Department of Internal Medicine, University of Genoa, Genoa, Italy
- IRCCS Ospedale Policlinico San Martino Genoa, Genoa, Italy
| | - Daniela Verzola
- Department of Internal Medicine, University of Genoa, Genoa, Italy
| | - Roberto Pontremoli
- Department of Internal Medicine, University of Genoa, Genoa, Italy
- IRCCS Ospedale Policlinico San Martino Genoa, Genoa, Italy
| | - Franesca Viazzi
- Department of Internal Medicine, University of Genoa, Genoa, Italy
- IRCCS Ospedale Policlinico San Martino Genoa, Genoa, Italy
| | | | | | - Aldo Pende
- Department of Internal Medicine, University of Genoa, Genoa, Italy
- IRCCS Ospedale Policlinico San Martino Genoa, Genoa, Italy
| | - Livia Pisciotta
- Department of Internal Medicine, University of Genoa, Genoa, Italy
- IRCCS Ospedale Policlinico San Martino Genoa, Genoa, Italy
| | - Fabrizio Montecucco
- IRCCS Ospedale Policlinico San Martino Genoa - Italian Cardiovascular Network, Italy
- Department of Internal Medicine and Centre of Excellence for Biomedical Research (CEBR), First Clinic of Internal Medicine, University of Genoa, Genoa, Italy
| | - Federico Carbone
- First Clinic of Internal Medicine, Department of Internal Medicine, University of Genoa, Genoa, Italy
- IRCCS Ospedale Policlinico San Martino Genoa - Italian Cardiovascular Network, Italy
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14
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Wu KC, Yu EW, Schafer AL. Skeletal health after bariatric surgery. MARCUS AND FELDMAN'S OSTEOPOROSIS 2021:1261-1280. [DOI: 10.1016/b978-0-12-813073-5.00051-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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Khalid SI, Omotosho PA, Spagnoli A, Torquati A. Association of Bariatric Surgery With Risk of Fracture in Patients With Severe Obesity. JAMA Netw Open 2020; 3:e207419. [PMID: 32520360 PMCID: PMC7287567 DOI: 10.1001/jamanetworkopen.2020.7419] [Citation(s) in RCA: 33] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
IMPORTANCE Given the complex relationship between body mass index, body composition, and bone density and the correlative nature of the studies that have established the prevailing notion that higher body mass indices may be protective against osteopenia and osteoporosis and, therefore, fracture, the absolute risk of fracture in patients with severe obesity who undergo either Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy (SG) compared with those who do not undergo bariatric surgery is unknown. OBJECTIVE To assess the rates of fractures associated with obesity and compare rates between those who do not undergo bariatric surgery, those who undergo RYGB, and those who undergo SG. DESIGN, SETTING, AND PARTICIPANTS In this retrospective multicenter cohort study of Medicare Standard Analytic Files derived from Medicare parts A and B records from January 2004 to December 2014, patients classified as eligible for bariatric surgery using the US Centers of Medicare & Medicaid criteria who either did not undergo bariatric surgery or underwent RYGB or SG were exactly matched in a 1:1 fashion based on their age, sex, Elixhauser Comorbidity Index, hypertension, smoking status, nonalcoholic fatty liver disease, hyperlipidemia, type 2 diabetes, osteoporosis, osteoarthritis, and obstructive sleep apnea status. Data were analyzed from November to December 2019. EXPOSURES RYGB or SG. MAIN OUTCOMES AND MEASURES The primary outcome measured in this study was the odds of fracture overall based on exposure to bariatric surgery. Secondary outcomes included the odds of type of fracture (humerus, radius or ulna, pelvis, hip, vertebrae, and total fractures) based on exposure to bariatric surgery. RESULTS A total of 49 113 patients were included and were equally made up of 16 371 bariatric surgery-eligible patients who did not undergo weight loss surgery, 16 371 patients who had undergone RYGB, and 16 371 patients who had undergone SG. Each group consisted of an equal number of 4109 men (25.1%) and 12 262 women (74.9%) and had an equal distribution of ages, with 11 780 patients (72.0%) 64 years or younger, 4230 (25.8%) aged 65 to 69 years, 346 (2.1%) aged 70 to 74 years, and 15 (0.1%) aged 75 to 79 years. Patients undergoing RYGB were found to have no significant difference in odds of fractures compared with bariatric surgery-eligible patients who did not undergo surgery. Patients undergoing undergone SG were found to have decreased odds of fractures of the humerus (odds ratio [OR], 0.57; 95% CI, 0.45-0.73), radius or ulna (OR, 0.38; 95% CI, 0.25-0.58), hip (OR, 0.49; 95% CI, 0.33-0.74), pelvis (OR, 0.34; 95% CI, 0.18-0.64), vertebrae (OR, 0.60; 95% CI, 0.48-0.74), or fractures in general (OR, 0.53; 95% CI, 0.46-0.62). Compared with patients undergoing SG, patients undergoing RYGB had a significantly greater risk of total fractures (OR, 1.79; 95% CI, 1.55-2.06) and humeral fractures (OR, 1.60; 95% CI, 1.24-2.07). CONCLUSIONS AND RELEVANCE In this cohort study, bariatric surgery was associated with a reduced risk of fracture in bariatric surgery-eligible patients. Sleeve gastrectomy might be the best option for weight loss in patients in which fractures could be a concern, as RYGB may be associated with an increased fracture risk compared with SG.
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Affiliation(s)
- Syed I. Khalid
- Department of Surgery, Rush University Medical Center, Chicago, Illinois
| | - Philip A. Omotosho
- Department of Surgery, Rush University Medical Center, Chicago, Illinois
| | - Anna Spagnoli
- Department of Surgery, Rush University Medical Center, Chicago, Illinois
| | - Alfonso Torquati
- Department of Surgery, Rush University Medical Center, Chicago, Illinois
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Abstract
PURPOSE OF REVIEW This review outlines the recent findings regarding the impact of bariatric surgery on bone. It explores potential mechanisms for skeletal changes following bariatric surgery and strategies for management. RECENT FINDINGS Bone loss following bariatric surgery is multifactorial. Probable mechanisms include skeletal unloading, abnormalities in calciotropic hormones, and changes in gut hormones. Skeletal changes that occur after bariatric surgery are specific to procedure type and persist for several years post-operatively. Studies suggest that while bone loss begins early, fracture risk may be increased later in the post-operative course, particularly after Roux-en-Y gastric bypass (RYGB). Further research is needed to assess the extent to which skeletal changes following bariatric surgery result in fragility. Current management should be geared toward prevention of bone loss, correction of nutritional deficiencies, and incorporation of weight bearing exercise. Pharmacologic treatment should be considered for high-risk patients.
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Affiliation(s)
- Alexandra N Krez
- Endocrinology and Metabolic Bone Disease Service, Hospital for Special Surgery New York, New York, USA
| | - Emily M Stein
- Endocrinology and Metabolic Bone Disease Service, Hospital for Special Surgery New York, New York, USA.
- Weill Cornell Medical College, 535 East 70th Street, New York, NY, 10021, USA.
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17
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Lu Y, Xu Y, Yuan W, Wang M, Zhou Y, Chen K, Huang Q. Downregulation of osteopontin inhibits browning of white adipose tissues through PI3K-AKT pathway in C57BL / 6 mice. Eur J Pharmacol 2020; 866:172822. [PMID: 31760068 DOI: 10.1016/j.ejphar.2019.172822] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2019] [Revised: 11/19/2019] [Accepted: 11/20/2019] [Indexed: 10/25/2022]
Abstract
Brown adipose tissue (BAT) plays important roles in regulating energy homeostasis and combating obesity. Accordingly, increasing the abundance and/or activating BAT would be effective and promising approaches to combat obesity and obesity-relative diseases. Our previous data in vitro have shown that osteopontin (OPN) induces the brown adipogenesis in 3T3-L1 cells via a phosphatidylinositol 3 kinase (PI3K)-AKT pathway. However, it is currently unknown whether OPN exerts such an effect on animals in vivo. Therefore, in the study we sought to investigate the pro-browning effects of OPN and to explore its underlying mechanisms by transfecting with Ad-GFP-aP2-OPN-shRNA to specifically down-regulate the OPN of white adipose tissue (WAT) in mice. Our present results show that downregulation of OPN in WAT exacerbates obesity and inhibits WAT-browning. Moreover, immunohistochemical results also exhibit that the downregulation of OPN significantly diminishes the expression and sub-cellular localization of UCP-1, PRDM16 and PGC-1α. Besides, the western blotting results reveal that the expression levels of PI3K, AKT-pS473 and PPARγ markedly reduce. Consequently, we conclude that the downregulation of OPN inhibits the browning of WAT through inhibiting the expression of PPARγ mediated by the PI3K-AKT pathway. The findings suggest that OPN is involved in regulation of WAT-browning and regulating its expression would become a potential strategy to combat obesity and obesity-relative metabolic diseases.
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Affiliation(s)
- Yi Lu
- Provincial Key Laboratory of Basic Pharmacology, Nanchang University, Nanchang, 330006, Jiangxi Province, PR China; Department of Pharmacology, School of Pharmaceutical Science, Nanchang University, Nanchang, 330006, Jiangxi Province, PR China
| | - Yuhong Xu
- The First Clinical Medical School, Nanchang University, Nanchang, 330006, Jiangxi Province, PR China
| | - Wanwan Yuan
- Provincial Key Laboratory of Basic Pharmacology, Nanchang University, Nanchang, 330006, Jiangxi Province, PR China; Department of Pharmacology, School of Pharmaceutical Science, Nanchang University, Nanchang, 330006, Jiangxi Province, PR China
| | - Mengxi Wang
- Provincial Key Laboratory of Basic Pharmacology, Nanchang University, Nanchang, 330006, Jiangxi Province, PR China; Department of Pharmacology, School of Pharmaceutical Science, Nanchang University, Nanchang, 330006, Jiangxi Province, PR China
| | - Yumeng Zhou
- Provincial Key Laboratory of Basic Pharmacology, Nanchang University, Nanchang, 330006, Jiangxi Province, PR China; Department of Pharmacology, School of Pharmaceutical Science, Nanchang University, Nanchang, 330006, Jiangxi Province, PR China
| | - Kai Chen
- Provincial Key Laboratory of Basic Pharmacology, Nanchang University, Nanchang, 330006, Jiangxi Province, PR China; Department of Pharmacology, School of Pharmaceutical Science, Nanchang University, Nanchang, 330006, Jiangxi Province, PR China
| | - Qiren Huang
- Provincial Key Laboratory of Basic Pharmacology, Nanchang University, Nanchang, 330006, Jiangxi Province, PR China; Department of Pharmacology, School of Pharmaceutical Science, Nanchang University, Nanchang, 330006, Jiangxi Province, PR China.
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A Pilot, Randomized Study in Women of Nutrition-Related Clinical Chemistry at 6 Weeks after Roux en Y Gastric Bypass: Comparison of Two Nutrition Support Plans. Obes Surg 2019; 29:2781-2789. [DOI: 10.1007/s11695-019-03895-4] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
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Gagnon C, Schafer AL. Bone Health After Bariatric Surgery. JBMR Plus 2018; 2:121-133. [PMID: 30283897 PMCID: PMC6124196 DOI: 10.1002/jbm4.10048] [Citation(s) in RCA: 128] [Impact Index Per Article: 18.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/24/2017] [Revised: 03/13/2018] [Accepted: 03/26/2018] [Indexed: 02/06/2023] Open
Abstract
Bariatric surgery results in long-term weight loss and improvement or resolution in obesity-related comorbidities. However, mounting evidence indicates that it adversely affects bone health. This review summarizes clinical research findings about the impact of bariatric surgery on skeletal outcomes. The literature is the largest and strongest for the Roux-en-Y gastric bypass (RYGB) procedure, as RYGB was the most commonly performed bariatric procedure worldwide until it was very recently overtaken by the sleeve gastrectomy (SG). Because SG is a newer procedure, its skeletal effects have not yet been well defined. Epidemiologic studies have now demonstrated an increased risk of fracture after RYGB and biliopancreatic diversion with duodenal switch, both of which include a malabsorptive component. As these epidemiologic data have emerged, patient-oriented studies have elucidated the bone tissue-level changes that may account for the heightened skeletal fragility. Bariatric surgery induces early and dramatic increases in biochemical markers of bone turnover. A notable feature of recent patient-oriented clinical studies is the application of advanced skeletal imaging modalities; studies address the limitations of dual-energy X-ray absorptiometry (DXA) by using quantitative computed tomography (QCT)-based modalities to examine volumetric bone mineral density and compartment-specific density and microstructure. RYGB results in pronounced declines in bone mass at the axial skeleton demonstrated by DXA and QCT, as well as at the appendicular skeleton demonstrated by high-resolution peripheral quantitative computed tomography (HR-pQCT). RYGB has detrimental effects on trabecular and cortical microarchitecture and estimated bone strength. Skeletal changes after RYGB appear early and continue even after weight loss plateaus and weight stabilizes. The skeletal effects of bariatric surgery are presumably multifactorial, and mechanisms may involve nutritional factors, mechanical unloading, hormonal factors, and changes in body composition and bone marrow fat. Clinical guidelines address bone health and may mitigate the negative skeletal effects of surgery, although more research is needed to direct and support such guidelines. © 2018 The Authors. JBMR Plus is published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.
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Affiliation(s)
- Claudia Gagnon
- Department of MedicineUniversité LavalQuebec CityCanada
- Endocrinology and Nephrology UnitCHU de Quebec Research CentreQuebec CityCanada
- Institute of Nutrition and Functional FoodsUniversité LavalQuebec CityCanada
- Quebec Heart and Lung Institute Research CentreQuébec CityCanada
| | - Anne L Schafer
- Department of MedicineUniversity of CaliforniaSan FranciscoCAUSA
- Department of Epidemiology and BiostatisticsUniversity of CaliforniaSan FranciscoCAUSA
- Endocrine Research UnitSan Francisco Veterans Affairs Heath Care SystemSan FranciscoCAUSA
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Abo El-Asrar M, Ismail EAR, Thabet RA, Kamel AS, NehmedAllah S. Osteopontin as a marker of vasculopathy in pediatric patients with type 1 diabetes mellitus: Relation to vascular structure. Pediatr Diabetes 2018; 19:1107-1115. [PMID: 29687557 DOI: 10.1111/pedi.12686] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/11/2018] [Revised: 04/16/2018] [Accepted: 04/16/2018] [Indexed: 01/03/2023] Open
Abstract
BACKGROUND Type 1 diabetes mellitus (T1DM) is associated with serious micro-vascular and macro-vascular complications. Osteopontin (OPN) has emerged as a strong predictor of incipient diabetic nephropathy and a first-ever cardiovascular event in adults with T1DM. OPN is linked to coronary atherosclerosis in type 2 diabetes. The aim of the study was to test the hypothesis that OPN could be a potential marker for micro-vascular complications in children and adolescents with T1DM and we assessed its relation to carotid and aortic intima media thickness (CIMT and AIMT) as non-invasive index for subclinical atherosclerosis. METHODS Eighty patients with T1DM ≤18 years were divided into 2 groups according to the presence of micro-vascular complications and compared with 40 age- and sex-matched healthy controls. Fasting blood glucose, high sensitivity C-reactive protein (hs-CRP), HbA1c, urinary albumin creatinine ratio (UACR), OPN, CIMT, and AIMT were assessed. RESULTS Both CIMT and AIMT were significantly higher in patients with and without micro-vascular complications compared with healthy controls (P < .001). OPN concentrations were significantly elevated in all diabetic patients compared with controls (P = .002). OPN was also significantly higher in patients with micro-vascular complications than patients without (P < .001) but levels were comparable among those without complications and controls (P = .322). Receiver operating characteristic curve analysis revealed that OPN cut-off value 90 ng/mL could differentiate patients with and without micro-vascular complications with 81.7% sensitivity and 95.8% specificity. Significant positive correlations were found between OPN and HbA1c, UACR, CIMT, and AIMT. CONCLUSIONS OPN could be considered a marker of vasculopathy and subclinical atherosclerosis in pediatric T1DM.
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Affiliation(s)
| | | | | | - Ashraf Sayed Kamel
- Pediatric Department, Faculty of Medicine, Fayoum University, Faiyum, Egypt
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Özdemir ZC, Düzenli Kar Y, Demiral M, Sırmagül B, Bör Ö, Kırel B. The Frequency of Metabolic Syndrome and Serum Osteopontin Levels in Survivors of Childhood Acute Lymphoblastic Leukemia. J Adolesc Young Adult Oncol 2018; 7:480-487. [PMID: 29641359 DOI: 10.1089/jayao.2017.0129] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Abstract
PURPOSE Metabolic syndrome (MetS) and obesity have increasingly been reported in survivors of childhood cancer. Osteopontin (OPN) is primarily synthesized in adipose tissue and is thought to have a role in obesity and the development of insulin resistance (IR). The aim of this study was to investigate the frequency of MetS in survivors of acute lymphoblastic leukemia (ALL) and to establish the relationship between serum OPN levels and anthropometric measurements and glucose metabolism. METHODS A total 50 survivors of ALL (median age: 10.5 years; post-treatment interval 4.54 ± 2.48 years), and 20 healthy children (median age: 11 years) were included in the study. Anthropometric measurements were taken, and serum glucose, insulin, homeostasis model assessment and IR index (HOMA-IR index), lipoprotein, thyroid hormone levels, and OPN levels were measured. RESULTS Twenty-one (42%) survivors were overweight/obese, 2 (5.1%) survivors had MetS, 7 (14%) survivors had IR, and 19 (38%) survivors had dyslipidemia. Fasting insulin levels and HOMA-IR of the overweight/obese survivors were significantly higher than those of the normal-weight survivors (p < 0.05 and p < 0.01) and control group (p < 0.01 and p < 0.01). The serum OPN level was significantly lower in the overweight/obese survivor than in the normal-weight survivor and control group (37.42 ng/mL [range, 27.32-62.07], 69.02 ng/mL [range, 40.29-88.21], and 85.7 ng/mL [range 67.7-102.3]; p < 0.01, p < 0.001, respectively). Serum OPN levels were inversely correlated with anthropometric measurements and HOMA-IR index in all the subjects. CONCLUSION Our results showed that obesity and IR are associated with decreased serum OPN levels in childhood survivors of ALL.
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Affiliation(s)
- Zeynep Canan Özdemir
- 1 Department of Pediatric Hematology/Oncology, Eskişehir Osmangazi University , Ekişehir, Turkey
| | - Yeter Düzenli Kar
- 1 Department of Pediatric Hematology/Oncology, Eskişehir Osmangazi University , Ekişehir, Turkey
| | - Meliha Demiral
- 2 Department of Pediatric Endocrinology, Eskişehir Osmangazi University , Ekişehir, Turkey
| | - Başar Sırmagül
- 3 Department of Pharmacology, Faculty of Medicine, Eskişehir Osmangazi University , Ekişehir, Turkey
| | - Özcan Bör
- 1 Department of Pediatric Hematology/Oncology, Eskişehir Osmangazi University , Ekişehir, Turkey
| | - Birgül Kırel
- 2 Department of Pediatric Endocrinology, Eskişehir Osmangazi University , Ekişehir, Turkey
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El-Din DSS, Amin AI, Egiza AO. Utility of Tissue Inhibitor Metalloproteinase-1 and Osteopontin as Prospective Biomarkers of Early Cardiovascular Complications in Type 2 Diabetes. Open Access Maced J Med Sci 2018. [PMID: 29531595 PMCID: PMC5839439 DOI: 10.3889/oamjms.2018.081] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/02/2023] Open
Abstract
AIM: This work investigated associations between tissue inhibitor metalloproteinase-1 and diabetic cardiovascular diseases in type 2 diabetic patients; also it investigated the role of osteopontin in the diagnosis of type 2 cardiovascular diabetes complications. SUBJECTS AND METHODS: These were examined on eighty subjects, divided into three groups as follows: twenty volunteer healthy control subjects, thirty type 2 diabetes mellitus (DM) patients, and thirty cardiovascular, diabetic patients. Full clinical measurements were carried out, and the expression level of tissue inhibitor metalloproteinase-1 in blood samples was analysed by real-time PCR, using gene-specific primer pairs. Also osteopontin concentrations had been measured by the enzyme-linked immunosorbent assay. Data were tested statistically by parametric tests. RESULTS: The concentrations of osteopontin and the expression levels of tissue inhibitor metalloproteinase-1 were significantly increased in diabetic and cardiovascular diabetic groups compared to control group also they were significantly increased in the cardiovascular diabetic group compared to the diabetic group. CONCLUSION: Tissue inhibitor metalloproteinase-1 and osteopontin concentrations were significantly increased in diabetic patients with cardiovascular complications than other groups.
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Corbeels K, Verlinden L, Lannoo M, Simoens C, Matthys C, Verstuyf A, Meulemans A, Carmeliet G, Van der Schueren B. Thin bones: Vitamin D and calcium handling after bariatric surgery. Bone Rep 2018; 8:57-63. [PMID: 29955623 PMCID: PMC6019966 DOI: 10.1016/j.bonr.2018.02.002] [Citation(s) in RCA: 37] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/10/2017] [Revised: 01/25/2018] [Accepted: 02/01/2018] [Indexed: 02/06/2023] Open
Abstract
Bariatric surgery has proven to be a valuable treatment option for morbid obesity. However, these procedures can lead to impaired intestinal absorption of calcium and vitamin D, thereby challenging calcium homeostasis and possibly contributing to bone loss leading to an increased fracture risk. Besides calcium and vitamin D malabsorption, hormonal changes occurring after surgery can also be the source of observed bone loss. In this review, first, a case report will be discussed, highlighting the relevance of this topic. Afterwards, changes in bone density and fracture risk, after the two most performed types of bariatric surgery, Sleeve Gastrectomy (SG) and Roux-en-Y Gastric Bypass (RYGB) will be discussed. In addition, we discuss the putative underlying mechanisms leading to bone changes based on both preclinical and clinical observations. Nonetheless, it is clear further research is needed to further elucidate the exact mechanisms of bone loss following bariatric surgery and subsequently identify potential treatment options for bone preservation.
Bariatric surgery induces bone loss and leads to increased fracture risk. Bone resorption increases after both SG and, more strongly, after RYGB. Malabsorption and adipose tissue-related hormones likely contribute to bone loss.
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Affiliation(s)
- Katrien Corbeels
- KU Leuven, Department of Chronic Diseases, Metabolism & Ageing (CHROMETA), Clinical and Experimental Endocrinology, Leuven, Belgium
| | - Lieve Verlinden
- KU Leuven, Department of Chronic Diseases, Metabolism & Ageing (CHROMETA), Clinical and Experimental Endocrinology, Leuven, Belgium
| | - Matthias Lannoo
- KU Leuven, Department of Chronic Diseases, Metabolism & Ageing (CHROMETA), Clinical and Experimental Endocrinology, Leuven, Belgium
| | - Caroline Simoens
- KU Leuven, Department of Chronic Diseases, Metabolism & Ageing (CHROMETA), Clinical and Experimental Endocrinology, Leuven, Belgium.,KU Leuven, Department of Cellular and Molecular Medicine, Laboratory of Ion Channel Research, VIB Center for Brain and Disease Research, Leuven, Belgium
| | - Christophe Matthys
- KU Leuven, Department of Chronic Diseases, Metabolism & Ageing (CHROMETA), Clinical and Experimental Endocrinology, Leuven, Belgium
| | - Annemieke Verstuyf
- KU Leuven, Department of Chronic Diseases, Metabolism & Ageing (CHROMETA), Clinical and Experimental Endocrinology, Leuven, Belgium
| | - Ann Meulemans
- KU Leuven, Department of Chronic Diseases, Metabolism & Ageing (CHROMETA), Clinical and Experimental Endocrinology, Leuven, Belgium
| | - Geert Carmeliet
- KU Leuven, Department of Chronic Diseases, Metabolism & Ageing (CHROMETA), Clinical and Experimental Endocrinology, Leuven, Belgium
| | - Bart Van der Schueren
- KU Leuven, Department of Chronic Diseases, Metabolism & Ageing (CHROMETA), Clinical and Experimental Endocrinology, Leuven, Belgium
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Cassuto J, Folestad A, Göthlin J, Malchau H, Kärrholm J. The key role of proinflammatory cytokines, matrix proteins, RANKL/OPG and Wnt/β-catenin in bone healing of hip arthroplasty patients. Bone 2018; 107:66-77. [PMID: 29129760 DOI: 10.1016/j.bone.2017.11.004] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/28/2017] [Revised: 10/01/2017] [Accepted: 11/08/2017] [Indexed: 01/08/2023]
Abstract
INTRODUCTION We still lack understanding of why some implants fail while most remain stable after decades of use. Proinflammatory cytokines, matrix proteins and bone regulating cytokines of the RANKL/OPG (receptor activator of nuclear factor kappa B ligand/osteoprotegerin) and Wnt/β-catenin pathways are mandatory for normal bone repair but their spatial and temporal role in the healing of primary total hip arthroplasties (THA) has not been previously shown. MATERIALS AND METHODS Twenty-four osteoarthritis patients with one-sided well-fixed primary THA were prospectively monitored during 18years (18Y) with repeated blood samples, clinical variables and radiographs. Eighty-one healthy donors divided in three age- and gender-matched groups and twenty osteoarthritis patients awaiting THA and serving as control of the validity of stored plasma in THA patients, were included. Plasma was analyzed for C-reactive protein (CRP), interleukin (IL)-6, IL-8, IL-1β, tumor necrosis factor (TNF)-α, osteopontin (OPN), secreted protein acidic and rich in cysteine (SPARC/osteonectin), osteocalcin (OC), bone specific alkaline phosphatase (BALP), N-terminal propeptide of collagen type I (P1NP), RANKL, OPG, the Wnt agonistic ligands (Wnt)-1 and Wnt-3a, and the Wnt antagonists sclerostin, Dickkopf (Dkk)-1, Dkk-3, Dkk-4, secreted frizzled related protein (sFRP)-1, sFRP-3 and Wnt inhibitory factor-1 (Wif-1). RESULTS Inflammatory mediators in arthroplasty patients (CRP, IL-6, OPN) increased significantly on day one after surgery vs preoperative value (PR) and healthy subjects and returned to baseline at 6W. TNF-α did not change relative preoperative level or healthy subjects. SPARC and OC increased in a biphasic fashion with the primary phase beginning shortly after surgery and lasting 3M (SPARC) and 2Y (OC) while the secondary phase peaked at 1Y (SPARC) and 13Y (OC), with both returning to basal level at 15Y. BALP peaked at 3M after surgery with a return to basal level at 2Y followed by a continuous increase from 5Y until 18Y. P1NP increased immediately after surgery and returned to basal level at 6W followed by a new peak at 10Y returning to basal at 13Y. IL-8 and IL-1β peaked at 5Y post-THA and returned to basal level at 10Y. RANKL/OPG and Wnt/β-catenin remained at preoperative levels until 5Y post-THA when a sustained increase in OPG level, paralleled by a sustained decrease in sclerostin, started and lasted until 18Y. Despite a strong increase by RANKL at 13Y, the OPG/RANKL-ratio remained high between 5Y and 18Y. Dkk-1 and sFRP-1 remained at basal level until 5Y followed by a peak at 7Y and a return to basal level at 15Y. Similarly, RANKL increased after 5Y, peaked at 13Y and returned to basal levels at 18Y, thus coinciding with Wnt-1. In contrast, Wnt3a, Dkk-3, Dkk-4, sFRP-3 and Wif-1 did not differ from preoperative levels or healthy subjects during the course of the follow-up. CONCLUSION The primary peak of proinflammatory cytokines involved in the initiation of bone healing after trauma is in line with previous results. The primary phase of increased matrix proteins, P1NP and BALP paralleled by RANKL, OPG and Wnt/β-catenin remaining at preoperative level until 5Y, support a strong formation of mineralized matrix and to a lesser degree bone during this phase. The secondary proinflammatory peak at 5Y is likely a trigger of coupled bone remodeling and neosynthesis as it is followed by increased levels of the bone anabolic turnover marker, BALP, and mediators of the RANKL/OPG and Wnt/β-catenin pathways. A continuous increase by OPG level and the bone turnover marker, BALP, lasting from 5Y until 18Y and paralleled by a similar decrease in sclerostin level support their being key regulators of bone anabolism, whereas the transient and opposed activities of RANKL, Wnt-1, Dkk-1 and sFRP-1 serve as fine tuning tools during the coupled remodeling phase.
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Affiliation(s)
- Jean Cassuto
- Orthopedic Research Unit, Department of Orthopedic Surgery, Sahlgrenska University Hospital, Mölndal, Sweden; Institution of Clinical Sciences, Göteborg University, Göteborg, Sweden.
| | - Agnetha Folestad
- Department of Orthopedics, CapioLundby Hospital, Göteborg, Sweden
| | - Jan Göthlin
- Department of Radiology, Sahlgrenska University Hospital, Mölndal, Sweden; Institution of Clinical Sciences, Göteborg University, Göteborg, Sweden
| | - Henrik Malchau
- Orthopedic Research Unit, Department of Orthopedic Surgery, Sahlgrenska University Hospital, Mölndal, Sweden; Department of Orthopedic Surgery, Harvard Medical School, Boston, USA
| | - Johan Kärrholm
- Orthopedic Research Unit, Department of Orthopedic Surgery, Sahlgrenska University Hospital, Mölndal, Sweden; Institution of Clinical Sciences, Göteborg University, Göteborg, Sweden
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Saklamaz A, Akyıldız M, Kasap E, Cengiz H. Gestasyonel diabetes mellitusta osteopontin seviyeleri artmaz. EGE TIP DERGISI 2017. [DOI: 10.19161/etd.395216] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022] Open
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Yu EW, Wewalka M, Ding SA, Simonson DC, Foster K, Holst JJ, Vernon A, Goldfine AB, Halperin F. Effects of Gastric Bypass and Gastric Banding on Bone Remodeling in Obese Patients With Type 2 Diabetes. J Clin Endocrinol Metab 2016; 101:714-22. [PMID: 26600045 PMCID: PMC4880129 DOI: 10.1210/jc.2015-3437] [Citation(s) in RCA: 60] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
CONTEXT Roux-en-Y gastric bypass (RYGB) leads to high-turnover bone loss, but little is known about skeletal effects of laparoscopic adjustable gastric banding (LAGB) or mechanisms underlying bone loss after bariatric surgery. OBJECTIVE To evaluate effects of RYGB and LAGB on fasting and postprandial indices of bone remodeling. DESIGN AND SETTING Ancillary investigation of a prospective study at 2 academic institutions. PARTICIPANTS Obese adults aged 21-65 years with type 2 diabetes who underwent RYGB (n = 11) or LAGB (n = 8). OUTCOMES Serum C-terminal telopeptide (CTX), procollagen type 1 N-terminal propeptide (P1NP), and PTH were measured during a mixed meal tolerance test at baseline, 10 days and 1 year after surgery. Changes in 25-hydroxyvitamin D, polypeptide YY (PYY), glucagon-like peptide-1, glucose-dependent insulinotropic peptide, and insulin were also assessed. RESULTS Fasting CTX increased 10 days after RYGB but not LAGB (+69 ± 23% vs +12±12%, P < .001), despite comparable weight loss at that time. By 1 year, fasting CTX and P1NP increased more after RYGB than LAGB (CTX +221 ± 60% vs +15 ± 6%, P<0.001; P1NP +93 ± 25% vs -9 ± 10%, P < .001) and weight loss was greater with RYGB. Changes in CTX were independent of PTH and 25-hydroxyvitamin D but were associated with increases in fasting PYY. Postprandial suppression of CTX was more pronounced after RYGB than LAGB at 10 days and 1 year postoperatively. CONCLUSIONS RYGB is accompanied by early increases in fasting indices of bone remodeling, independent of weight loss or changes in PTH or 25-hydroxyvitamin D. LAGB did not affect bone markers. PYY and other enterohormonal signals may play a role in RYGB-specific skeletal changes.
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Affiliation(s)
- Elaine W Yu
- Endocrine Unit (E.W.Y.), Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114; Research Division (M.W., S.-A.D., K.F., A.B.G.), Joslin Diabetes Center, Harvard Medical School, Boston, Massachusetts 02215; Division of Endocrinology (D.C.S., A.B.G., F.H.), Diabetes, and Hypertension, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115; Novo Nordisk Foundation Center for Basic Metabolic Research and Department of Biomedical Sciences (J.J.H.), University of Copenhagen, Denmark; and Center for Metabolic and Bariatric Surgery (A.V.), Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115
| | - Marlene Wewalka
- Endocrine Unit (E.W.Y.), Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114; Research Division (M.W., S.-A.D., K.F., A.B.G.), Joslin Diabetes Center, Harvard Medical School, Boston, Massachusetts 02215; Division of Endocrinology (D.C.S., A.B.G., F.H.), Diabetes, and Hypertension, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115; Novo Nordisk Foundation Center for Basic Metabolic Research and Department of Biomedical Sciences (J.J.H.), University of Copenhagen, Denmark; and Center for Metabolic and Bariatric Surgery (A.V.), Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115
| | - Su-Ann Ding
- Endocrine Unit (E.W.Y.), Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114; Research Division (M.W., S.-A.D., K.F., A.B.G.), Joslin Diabetes Center, Harvard Medical School, Boston, Massachusetts 02215; Division of Endocrinology (D.C.S., A.B.G., F.H.), Diabetes, and Hypertension, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115; Novo Nordisk Foundation Center for Basic Metabolic Research and Department of Biomedical Sciences (J.J.H.), University of Copenhagen, Denmark; and Center for Metabolic and Bariatric Surgery (A.V.), Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115
| | - Donald C Simonson
- Endocrine Unit (E.W.Y.), Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114; Research Division (M.W., S.-A.D., K.F., A.B.G.), Joslin Diabetes Center, Harvard Medical School, Boston, Massachusetts 02215; Division of Endocrinology (D.C.S., A.B.G., F.H.), Diabetes, and Hypertension, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115; Novo Nordisk Foundation Center for Basic Metabolic Research and Department of Biomedical Sciences (J.J.H.), University of Copenhagen, Denmark; and Center for Metabolic and Bariatric Surgery (A.V.), Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115
| | - Kathleen Foster
- Endocrine Unit (E.W.Y.), Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114; Research Division (M.W., S.-A.D., K.F., A.B.G.), Joslin Diabetes Center, Harvard Medical School, Boston, Massachusetts 02215; Division of Endocrinology (D.C.S., A.B.G., F.H.), Diabetes, and Hypertension, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115; Novo Nordisk Foundation Center for Basic Metabolic Research and Department of Biomedical Sciences (J.J.H.), University of Copenhagen, Denmark; and Center for Metabolic and Bariatric Surgery (A.V.), Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115
| | - Jens J Holst
- Endocrine Unit (E.W.Y.), Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114; Research Division (M.W., S.-A.D., K.F., A.B.G.), Joslin Diabetes Center, Harvard Medical School, Boston, Massachusetts 02215; Division of Endocrinology (D.C.S., A.B.G., F.H.), Diabetes, and Hypertension, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115; Novo Nordisk Foundation Center for Basic Metabolic Research and Department of Biomedical Sciences (J.J.H.), University of Copenhagen, Denmark; and Center for Metabolic and Bariatric Surgery (A.V.), Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115
| | - Ashley Vernon
- Endocrine Unit (E.W.Y.), Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114; Research Division (M.W., S.-A.D., K.F., A.B.G.), Joslin Diabetes Center, Harvard Medical School, Boston, Massachusetts 02215; Division of Endocrinology (D.C.S., A.B.G., F.H.), Diabetes, and Hypertension, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115; Novo Nordisk Foundation Center for Basic Metabolic Research and Department of Biomedical Sciences (J.J.H.), University of Copenhagen, Denmark; and Center for Metabolic and Bariatric Surgery (A.V.), Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115
| | - Allison B Goldfine
- Endocrine Unit (E.W.Y.), Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114; Research Division (M.W., S.-A.D., K.F., A.B.G.), Joslin Diabetes Center, Harvard Medical School, Boston, Massachusetts 02215; Division of Endocrinology (D.C.S., A.B.G., F.H.), Diabetes, and Hypertension, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115; Novo Nordisk Foundation Center for Basic Metabolic Research and Department of Biomedical Sciences (J.J.H.), University of Copenhagen, Denmark; and Center for Metabolic and Bariatric Surgery (A.V.), Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115
| | - Florencia Halperin
- Endocrine Unit (E.W.Y.), Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114; Research Division (M.W., S.-A.D., K.F., A.B.G.), Joslin Diabetes Center, Harvard Medical School, Boston, Massachusetts 02215; Division of Endocrinology (D.C.S., A.B.G., F.H.), Diabetes, and Hypertension, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115; Novo Nordisk Foundation Center for Basic Metabolic Research and Department of Biomedical Sciences (J.J.H.), University of Copenhagen, Denmark; and Center for Metabolic and Bariatric Surgery (A.V.), Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115
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Gursoy UK, Liukkonen J, Jula A, Huumonen S, Suominen AL, Puukka P, Könönen E. Associations Between Salivary Bone Metabolism Markers and Periodontal Breakdown. J Periodontol 2015; 87:367-75. [PMID: 26609698 DOI: 10.1902/jop.2015.150399] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Abstract
BACKGROUND A dual relationship between glycemic status and bone remodeling was suggested recently. The present study aimed to 1) analyze salivary levels of receptor activator for nuclear factor κ-B ligand (RANKL), osteoprotegerin, osteocalcin, and osteopontin as potential biomarkers of alveolar bone loss and 2) determine whether the glycemic status affects the relationship between bone remodeling markers and periodontal status. METHODS Salivary levels of RANKL, osteoprotegerin, osteocalcin, osteopontin, and serum glycosylated hemoglobin A1c, insulin, and glucose were analyzed in 220 participants divided into four groups according to their periodontal health status: 1) 79 participants had at least 14 teeth with probing depth (PD) ≥4 mm (generalized periodontitis [GP]); 2) 65 participants had either two or seven teeth with PD ≥4 mm (two groups of localized periodontitis [LP1 and LP2, respectively]); and 3) 76 participants had no teeth with PD ≥4 mm (non-periodontitis control group). RESULTS Salivary concentrations of RANKL, osteocalcin, and osteopontin were higher, and osteoprotegerin was lower in females than in males. Salivary osteoprotegerin concentrations were higher in the GP and LP2 groups than in the control group, whereas RANKL, osteocalcin, and osteopontin were not related with periodontal status. Salivary osteopontin correlated positively with serum and salivary insulin. The association observed between increased osteoprotegerin concentrations and periodontitis was lost after salivary insulin was included into the analyses as a confounding factor. CONCLUSIONS Salivary concentrations of bone markers are either affected by glycemic status or detected at very low levels. These factors hinder their use as salivary biomarkers of periodontitis.
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Affiliation(s)
- Ulvi K Gursoy
- Institute of Dentistry, University of Turku, Turku, Finland
| | | | - Antti Jula
- Department of Diagnostic Imaging, Turku University Hospital, Turku, Finland
| | - Sisko Huumonen
- Institute of Dentistry, University of Turku, Turku, Finland.,National Institute for Health and Welfare, Turku, Finland
| | - Anna L Suominen
- Unit of Living Conditions, Health, and Wellbeing and Department of Environmental Health in Environmental Epidemiology Unit; National Institute for Health and Welfare; Kuopio, Finland.,Institute of Dentistry, University of Eastern Finland, Kuopio, Finland.,Department of Oral and Maxillofacial Surgery, Kuopio University Hospital, Kuopio, Finland
| | - Pauli Puukka
- Department of Diagnostic Imaging, Turku University Hospital, Turku, Finland
| | - Eija Könönen
- Institute of Dentistry, University of Turku, Turku, Finland.,Oral Health Care, Welfare Division, City of Turku, Turku, Finland
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Osteopontin, CCL5 and CXCL9 are independently associated with psoriasis, regardless of the presence of obesity. Cytokine 2015; 74:287-92. [DOI: 10.1016/j.cyto.2015.04.015] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2014] [Revised: 04/21/2015] [Accepted: 04/22/2015] [Indexed: 12/30/2022]
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Raffaelli M, Iaconelli A, Nanni G, Guidone C, Callari C, Fernandez Real JM, Bellantone R, Mingrone G. Effects of biliopancreatic diversion on diurnal leptin, insulin and free fatty acid levels. Br J Surg 2015; 102:682-90. [DOI: 10.1002/bjs.9780] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2014] [Revised: 11/03/2014] [Accepted: 01/13/2015] [Indexed: 12/25/2022]
Abstract
Abstract
Background
Free fatty acid (FFA) levels are raised in obesity as a consequence of increased production and reduced clearance. They may link obesity with insulin resistance. Bariatric surgery can result in considerable weight loss and reduced insulin resistance, but the mechanism of action is not well understood. Although drugs such as metformin that lower insulin resistance can contribute to weight loss, a better understanding of the links between obesity, weight loss and changes in insulin resistance might lead to new approaches to patient management.
Methods
Variations in circulating levels of leptin, insulin and FFAs over 24 h were studied in severely obese (body mass index over 40 kg/m2) women before and 6 months after biliopancreatic diversion (BPD). Body composition was measured by dual-energy X-ray absorptiometry. A euglycaemic–hyperinsulinaemic clamp was used to assess insulin sensitivity. Levels of insulin, leptin and FFAs were measured every 20 min for 24 h. Pulsatile hormone and FFA analyses were performed.
Results
Among eight patients studied, insulin sensitivity more than doubled after BPD, from mean(s.d.) 39·78(7·74) to 96·66(27·01) mmol per kg fat-free mass per min, under plasma insulin concentrations of 102·29(9·60) and 93·61(9·95) µunits/ml respectively. The secretory patterns of leptin were significantly different from random but not statistically different before and after BPD, with the exception of the pulse height which was reduced after surgery. Both plasma insulin and FFA levels were significantly higher throughout the study day before BPD. Based on Granger statistical modelling, lowering of daily FFA levels was linked to decreased circulating leptin concentrations, which in turn were related to the lowering of daily insulin excursions. Multiple regression analysis indicated that FFA level was the only predictor of leptin level.
Conclusion
Lowering of circulating levels of FFAs after BPD may be responsible for the reduction in leptin secretion, which in turn can decrease circulating insulin levels. Surgical relevanceInsulin resistance is a common feature of obesity and type II diabetes. These patients are also relatively insensitive to the biological effects of leptin, a satiety hormone produced mainly in subcutaneous fat.Biliopancreatic diversion, a malabsorptive bariatric operation that drastically reduces circulating lipid levels, improves insulin resistance independently of weight loss. The mechanism of action, however, has still to be elucidated.This study demonstrated that normalization of insulin sensitivity after bariatric surgery was associated with a reduction in 24-h free fatty acid concentrations and changes in the pattern of leptin peaks in plasma. Bariatric surgery improves the metabolic dysfunction of obesity, and this may be through a reduction in circulating free fatty acids and modification of leptin metabolism.
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Affiliation(s)
- M Raffaelli
- Departments of Surgery, Catholic University of Rome, Rome, Italy
| | - A Iaconelli
- Departments of Internal Medicine, Catholic University of Rome, Rome, Italy
| | - G Nanni
- Departments of Surgery, Catholic University of Rome, Rome, Italy
| | - C Guidone
- Departments of Internal Medicine, Catholic University of Rome, Rome, Italy
| | - C Callari
- Departments of Surgery, Catholic University of Rome, Rome, Italy
| | - J M Fernandez Real
- Biomedical Research Institute of Girona (IDIBGI), CIBERobn Obesity Hospital of Girona ‘Dr Josep Trueta’, Girona, Spain
| | - R Bellantone
- Departments of Surgery, Catholic University of Rome, Rome, Italy
| | - G Mingrone
- Departments of Internal Medicine, Catholic University of Rome, Rome, Italy
- Department of Diabetes and Nutritional Sciences, Faculty of Life Sciences and Medicine, King's College, London, UK
- Medizinische Klinik und Poliklinik III, Universitätsklinikum Carl Gustav Carus an der Technischen Universität Dresden, Dresden, Germany
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Scibora LM. Skeletal effects of bariatric surgery: examining bone loss, potential mechanisms and clinical relevance. Diabetes Obes Metab 2014; 16:1204-13. [PMID: 25132010 DOI: 10.1111/dom.12363] [Citation(s) in RCA: 35] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/28/2014] [Revised: 07/27/2014] [Accepted: 07/29/2014] [Indexed: 02/06/2023]
Abstract
Bariatric surgery is the most effective therapeutic approach to morbid obesity, resulting in substantial weight loss and improved cardiometabolic profiles; however, a growing body of evidence suggests that bariatric procedures increase both skeletal fragility and the risk of related future fracture secondary to excessive bone loss. Prospective evidence shows that areal bone mineral density (BMD) assessed by dual energy X-ray absorptiometry (DXA) declines by as much as 14% in the proximal femoral regions, including the femoral neck and total hip, 12 months postoperatively. Lumbar spine areal BMD outcomes show greater 12-month postoperative variability across surgical procedures (-8 to +6%) and contrast with no change in volumetric BMD outcomes measured by quantitative computed tomography. Diminished mechanical loading, micronutrient deficiency and malabsorption, along with neurohormonal alterations, offer plausible underlying mechanisms to explain these observed post-bariatric bone changes, but most remain largely unsubstantiated in this population. Importantly, DXA-based skeletal imaging may have limited utility in accurately detecting bone change in people undergoing bariatric surgery; partly because excessive tissue overlying bone increases the variability of areal BMD outcomes. Moreover, a paucity of fracture and osteoporosis incidence data raises questions about whether marked post-bariatric surgery bone loss is clinically relevant or a functional adaptation to skeletal unloading. Future studies that use technology which is able to accurately capture the site-specific volumetric BMD and bone architectural changes that underpin bone strength in people undergoing bariatric surgery, that consider mechanical load, and that better quantify long-term fracture and osteoporosis incidence are necessary to understand the actual skeletal effects of bariatric surgery.
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Affiliation(s)
- L M Scibora
- Health and Human Performance Department, University of St. Thomas, St. Paul, MN, USA
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Finelli C, Padula MC, Martelli G, Tarantino G. Could the improvement of obesity-related co-morbidities depend on modified gut hormones secretion? World J Gastroenterol 2014; 20:16649-16664. [PMID: 25469034 PMCID: PMC4248209 DOI: 10.3748/wjg.v20.i44.16649] [Citation(s) in RCA: 39] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/23/2014] [Revised: 05/27/2014] [Accepted: 06/25/2014] [Indexed: 02/06/2023] Open
Abstract
Obesity and its associated diseases are a worldwide epidemic disease. Usual weight loss cures - as diets, physical activity, behavior therapy and pharmacotherapy - have been continuously implemented but still have relatively poor long-term success and mainly scarce adherence. Bariatric surgery is to date the most effective long term treatment for morbid obesity and it has been proven to reduce obesity-related co-morbidities, among them nonalcoholic fatty liver disease, and mortality. This article summarizes such variations in gut hormones following the current metabolic surgery procedures. The profile of gut hormonal changes after bariatric surgery represents a strategy for the individuation of the most performing surgical procedures to achieve clinical results. About this topic, experts suggest that the individuation of the crosslink among the gut hormones, microbiome, the obesity and the bariatric surgery could lead to new and more specific therapeutic interventions for severe obesity and its co-morbidities, also non surgical.
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Yu EW. Bone metabolism after bariatric surgery. J Bone Miner Res 2014; 29:1507-18. [PMID: 24677277 PMCID: PMC4128478 DOI: 10.1002/jbmr.2226] [Citation(s) in RCA: 162] [Impact Index Per Article: 14.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/14/2014] [Revised: 03/07/2014] [Accepted: 03/12/2014] [Indexed: 12/24/2022]
Abstract
Bariatric surgery is a popular and effective treatment for severe obesity but may have negative effects on the skeleton. This review summarizes changes in bone density and bone metabolism from animal and clinical studies of bariatric surgery, with specific attention to Roux-en-Y gastric bypass (RYGB), adjustable gastric banding (AGB), and sleeve gastrectomy (SG). Skeletal imaging artifacts from obesity and weight loss are also considered. Despite challenges in bone density imaging, the preponderance of evidence suggests that bariatric surgery procedures have negative skeletal effects that persist beyond the first year of surgery, and that these effects vary by surgical type. The long-term clinical implications and current clinical recommendations are presented. Further study is required to determine mechanisms of bone loss after bariatric surgery. Although early studies focused on calcium/vitamin D metabolism and mechanical unloading of the skeleton, it seems likely that surgically induced changes in the hormonal and metabolic profile may be responsible for the skeletal phenotypes observed after bariatric surgery.
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Affiliation(s)
- Elaine W Yu
- Endocrine Unit, Massachusetts General Hospital, Boston, MA, USA
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Lancha A, Moncada R, Valentí V, Rodríguez A, Catalán V, Becerril S, Ramírez B, Méndez-Giménez L, Frühbeck G, Gómez-Ambrosi J. Effect of Sleeve Gastrectomy on Osteopontin Circulating Levels and Expression in Adipose Tissue and Liver in Rats. Obes Surg 2014; 24:1702-8. [DOI: 10.1007/s11695-014-1240-z] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/25/2022]
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Osteopontin: A novel regulator at the cross roads of inflammation, obesity and diabetes. Mol Metab 2014; 3:384-93. [PMID: 24944898 PMCID: PMC4060362 DOI: 10.1016/j.molmet.2014.03.004] [Citation(s) in RCA: 307] [Impact Index Per Article: 27.9] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/22/2014] [Revised: 03/10/2014] [Accepted: 03/13/2014] [Indexed: 02/06/2023] Open
Abstract
Since its first description more than 20 years ago osteopontin has emerged as an active player in many physiological and pathological processes, including biomineralization, tissue remodeling and inflammation. As an extracellular matrix protein and proinflammatory cytokine osteopontin is thought to facilitate the recruitment of monocytes/macrophages and to mediate cytokine secretion in leukocytes. Modulation of immune cell response by osteopontin has been associated with various inflammatory diseases and may play a pivotal role in the development of adipose tissue inflammation and insulin resistance. Here we summarize recent findings on the role of osteopontin in metabolic disorders, particularly focusing on diabetes and obesity.
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Comparative effects of gastric bypass and sleeve gastrectomy on plasma osteopontin concentrations in humans. Surg Endosc 2014; 28:2412-20. [PMID: 24622764 DOI: 10.1007/s00464-014-3490-1] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2013] [Accepted: 02/14/2014] [Indexed: 12/13/2022]
Abstract
BACKGROUND Bariatric surgery (BS) has proven to be an effective treatment for morbid obesity. Osteopontin (OPN) is a proinflammatory cytokine involved in the development of obesity. The aim of our study was to determine the effect of weight loss following BS on circulating levels of OPN in humans. METHODS Body composition and circulating concentrations of OPN and markers of bone metabolism were determined in obese patients who underwent Roux-en-Y gastric bypass (RYGB; n = 40) or sleeve gastrectomy (SG; n = 11). RESULTS Patients who underwent RYGB or SG showed decreased body weight (P < 0.001) and body fat percentage (P < 0.001) as well as lower insulin resistance. However, plasma OPN levels were significantly increased after RYGB (P < 0.001) but remained unchanged following SG (P = 0.152). Patients who underwent RYGB also showed significantly increased C-terminal telopeptide of type-I collagen (ICTP) (P < 0.01) and osteocalcin (P < 0.001) while bone mineral density tended to decrease (P = 0.086). Moreover, OPN concentrations were positively correlated with the bone resorption marker ICTP after surgery. On the other hand, patients who underwent SG showed significantly increased ICTP levels (P < 0.05), and the change in OPN was positively correlated with the change in ICTP and negatively with the change in vitamin D after surgery (P < 0.05). CONCLUSIONS RYGB increased circulating OPN levels, while they remained unaltered after SG. The increase in OPN levels after RYGB could be related to the increased bone resorption in relation to its well-known effects on bone of this malabsorptive procedure in comparison to the merely restrictive SG.
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Rega-Kaun G, Kaun C, Wojta J. More than a simple storage organ: adipose tissue as a source of adipokines involved in cardiovascular disease. Thromb Haemost 2013; 110:641-50. [PMID: 23846791 DOI: 10.1160/th13-03-0212] [Citation(s) in RCA: 35] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2013] [Accepted: 05/19/2013] [Indexed: 01/04/2023]
Abstract
Overweight and obesity in many countries have developed into a serious health problem by themselves and by their impact on other pathologies such as insulin resistance, type 2 diabetes, hypertension, heart disease and cancer. The modulation of these diseases by adipose tissue-derived biomolecules, so-called adipokines, could be the key to differentiate between metabolically healthy and unhealthy obesity. This review will discuss the pathophysiological role of selected adipokines, primarily focusing on cardiovascular diseases. Furthermore, we will highlight possible therapeutic approaches, which target these biomolecules.
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Affiliation(s)
- Gersina Rega-Kaun
- Johann Wojta, Department of Internal Medicine II, Medical University Vienna, Waehringer Guertel 18-20, A-1090 Vienna, Austria, Tel.: +43 1 40400 73500, Fax: +43 1 40400 73586, E-mail:
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You JS, Ji HI, Chang KJ, Yoo MC, Yang HI, Jeong IK, Kim KS. Serum osteopontin concentration is decreased by exercise-induced fat loss but is not correlated with body fat percentage in obese humans. Mol Med Rep 2013; 8:579-84. [PMID: 23764959 DOI: 10.3892/mmr.2013.1522] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2013] [Accepted: 06/11/2013] [Indexed: 11/05/2022] Open
Abstract
To evaluate the extent to which fat mass contributes to serum osteopontin (OPN) concentration, we investigated whether serum OPN levels are decreased by exercise-induced fat mass loss and whether they are associated with body fat percentage in obese humans. Twenty‑three female college students were recruited to participate in an 8‑week body weight control program. Body composition [body weight, soft lean mass, body fat mass, body fat percentage, waist-hip ratio and body mass index (BMI)] were assessed prior to and following the program. Serum lipid profiles and serum adiponectin, leptin and osteopontin levels were measured from serum collected prior to and following the program. To understand the effect of fat mass loss on the serum levels of adipokine, which is mainly produced in adipose tissue, the leptin and adiponectin levels were also measured prior to and following the program. Serum leptin levels (mean ± standard error of the mean) decreased significantly following the program (from 9.82±0.98 to 7.23±0.67 ng/ml) and were closely correlated with body fat percentage. In addition, serum adiponectin levels were negatively correlated with body fat percentage, while serum adiponectin levels were not significantly altered. By contrast, serum OPN levels decreased significantly following the program (from 16.03±2.34 to 10.65±1.22 ng/ml). However, serum OPN levels were not correlated with body fat percentage, suggesting that serum OPN levels are controlled by several other factors in humans. In conclusion, a high expression of OPN in adipose tissues may not be correlated with serum OPN levels in obese humans. Thus, tissues or physiological factors other than fat mass may have a greater contribution to the serum OPN levels.
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Affiliation(s)
- Jeong Soon You
- Department of Food and Nutrition, Inha University, Nam-gu, Incheon 402-751, Republic of Korea
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Falor AE, Zobel M, Kaji A, Neville A, De Virgilio C. Admission variables predictive of gangrenous cholecystitis. Am Surg 2012; 22:1648-57. [PMID: 23025944 DOI: 10.1007/s11695-012-0698-9] [Citation(s) in RCA: 36] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
The objective of the present study was to identify admission clinical factors associated with gangrenous cholecystitis (GC) and factors associated with conversion to open cholecystectomy. We retrospectively evaluated 391 patients over a 17-month period who underwent urgent laparoscopic cholecystectomy for a diagnosis of acute cholecystitis. Eighty-nine patients with pathologically proven GC were compared with 302 patients without GC. On multivariable logistic regression, predictors of GC included male gender, white blood cell count greater than 14,000/mm3, heart rate greater than 90 beats per minute, and sodium 135 mg/dL or less. Conversion rate to open cholecystectomy was 7.9 per cent overall, 4 per cent for non-GC, and 19 per cent for GC (odds ratio, 0.2; 95% confidence interval, 0.1 to 0.4; P<0.00001). Conversion was predicted by increasing number of days to surgery, total bilirubin, and white blood cell count. Complication rate was higher in the GC group (10.1 vs 3.6% in the acute cholecystitis group, P=0.01). The increased rate of conversion observed with surgery delay suggests that early laparoscopic cholecystectomy may be preferable in most patients.
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Affiliation(s)
- Ann E Falor
- Department of Surgery, Harbor-UCLA Medical Center, Torrance, California 90509, USA
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Schindler K, Vila G, Hoppichler F, Lechleitner M, Luger A, Anderwald C, Hoefler J, Tomasec G, Kautzky-Willer A, Ludvik B. The impact of type 2 diabetes on circulating adipokines in patients with metabolic syndrome. Obes Facts 2012; 5:270-6. [PMID: 22647307 DOI: 10.1159/000338729] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/27/2011] [Accepted: 08/26/2011] [Indexed: 01/13/2023] Open
Abstract
AIM The aim of the study was to investigate, whether type 2 diabetes independently influences adipokines and inflammatory markers in patients with metabolic syndrome. METHODS 36 patients with metabolic syndrome without type 2 diabetes and 39 patients with metabolic syndrome with type 2 diabetes, carefully matched for age, sex, and BMI, were investigated. Primary outcome measures were circulating adipokines and inflammatory markers (adiponectin, leptin, visfatin, vaspin, resistin, TNF-α, IL-6, monocyte chemoattractant protein-1 (MCP-1), retinol binding protein 4 (RBP-4), growth differentiation factor-15 (GDF-15)). In addition, we determined parameters of glucose and lipid metabolism. RESULTS Patients with metabolic syndrome and type 2 diabetes had significantly lower levels of plasma total cholesterol, low-density lipoprotein cholesterol and triglycerides (p < 0.05). They displayed higher GDF-15 concentrations (1,113 ± 135 vs. 656 ± 63 pg/ml, p = 0.005) and lower visfatin concentrations (3.7 ± 0.3 vs. 4.8 ± 0.2 ng/ml, p = 0.009). There were no differences in other adipokines and inflammatory markers between both groups. CONCLUSIONS In patients with metabolic syndrome, type 2 diabetes leads to decreased visfatin and increased GDF-15 serum levels when compared to carefully matched non-diabetic subjects. Whether the increase in GDF-15 is an indicator or a causal factor for the increased cardiovascular risk in diabetic subjects remains to be investigated in further studies.
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Affiliation(s)
- Karin Schindler
- Division of Endocrinology and Metabolism, Department of Internal Medicine III, Medical University Vienna, Vienna, Austria
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Metabolic surgery-principles and current concepts. Langenbecks Arch Surg 2011; 396:949-72. [PMID: 21870176 DOI: 10.1007/s00423-011-0834-3] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2011] [Accepted: 08/01/2011] [Indexed: 12/19/2022]
Abstract
INTRODUCTION In the almost six decades of bariatric surgery, a variety of surgical approaches to treating morbid obesity have been developed. HISTORY AND EVOLUTION Rather than prior techniques being continually superseded by new ones, a broad choice of surgical solutions based on restrictive, malabsorptive, humoral effects, or combinations thereof, is now available. In fact, in recent years, the advent of surgically modifying human metabolism promises new approaches to ameliorate traditionally medically treated metabolic entities, i.e., diabetes, even in the non-obese. The understanding of the various metabolic effects have led to a paradigm shift from bariatric surgery as a solely weight-reducing procedure to metabolic surgery affecting whole body metabolism. CONCLUSION The bariatric surgeon now faces the challenge and opportunity of selecting the most suitable technique for each individual case. To assist in such decision-making, this review, Metabolic surgery-principles and current concepts, is presented, tracing the historical development; describing the various surgical techniques; elucidating the mechanisms by which glycemic control can be achieved that involve favorable changes in insulin secretion and insulin sensitivity, gut hormones, adipokines, energy expenditure, appetite, and preference for low glycemic index foods; as well as exploring the fascinating future potential of this new interdisciplinary field.
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Komorowski J, Jankiewicz-Wika J, Kolomecki K, Cywinski J, Piestrzeniewicz K, Swiętoslawski J, Stepien H. Systemic blood osteopontin, endostatin, and E-selectin concentrations after vertical banding surgery in severely obese adults. Cytokine 2011; 55:56-61. [PMID: 21486700 DOI: 10.1016/j.cyto.2011.03.020] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2010] [Revised: 03/11/2011] [Accepted: 03/18/2011] [Indexed: 11/24/2022]
Abstract
BACKGROUND Obesity is associated with endothelial dysfunction and increased inflammation as well as with expansion of the capillary bed in regional adipose deposits, and a balance between these factors is involved in angiogenesis. Osteopontin (OPN) is a proinflammatory cytokine involved in regulating immune processes and mediating chronic inflammation. Its level is usually elevated in the plasma and adipose tissue of obese subjects. E-selectin, an adhesion molecule which is released by dysfunctional endothelial cells, is believed to be a marker of an early atherosclerotic process. Endostatin (END), an angiogenesis inhibitor, is present in the blood of obese subjects. The most effective treatment to achieve weight loss in morbidly obese subjects is bariatric surgery. The aim of the study was to evaluate and compare the circulating concentrations of OPN, E-selectin and END as well as the insulin resistance (HOMA-IR) of severely obese patients with metabolic syndrome before and after vertical banded gastroplasty (VBG). MATERIAL AND METHODS The test cohorts comprised eight males and 20 females (total 28 patients) aged from 20 to 59 years with simple obesity and the presence of metabolic syndrome, both before and 3, 6, 12, 24 months after bariatric surgery (six patients were also checked after 36 and four after 48 months). RESULTS Bariatric surgery significantly reduced (over 24 months) body weight, BMI, waist circumference, HOMA-IR and blood concentrations of CRP. Plasma OPN gradually increased after VBG and E-selectin in systemic blood decreased. We did not observe any differences in END concentrations from 12 to 48 months after surgery. CONCLUSION VBG improves metabolic syndrome parameters, decreases E-selectin and gradually increases OST blood concentrations but it does not have any significant influence on END levels.
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Affiliation(s)
- Jan Komorowski
- Department of Clinical Endocrinology, First Chair of Endocrinology, Medical University of Lodz, 91-425 Lodz, Sterlinga 1/3, Poland.
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Beckman LM, Beckman TR, Sibley SD, Thomas W, Ikramuddin S, Kellogg TA, Ghatei MA, Bloom SR, le Roux CW, Earthman CP. Changes in gastrointestinal hormones and leptin after Roux-en-Y gastric bypass surgery. JPEN J Parenter Enteral Nutr 2011; 35:169-80. [PMID: 21378246 PMCID: PMC4284080 DOI: 10.1177/0148607110381403] [Citation(s) in RCA: 63] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND Roux-en-Y gastric bypass (RYGB) imparts long-term weight loss, the mechanisms for which are not well understood. Changes in leptin and gastrointestinal (GI) hormones, including glucagon-like peptide 1 (GLP-1), peptide YY (PYY), and ghrelin, may contribute to the relative success of RYGB compared with conventional weight loss methods. This study evaluated changes in GI hormones and leptin post-RYGB. The study also evaluated whether GI hormones differed after a short-term dose of protein or fat. METHODS GLP-1, PYY, ghrelin, and leptin were assessed in 16 women before RYGB and up to 1 year after RYGB. Plasma was collected before and at several times after a short-term equicaloric dose of protein or fat. RESULTS GLP-1 area under the curve (AUC) increased at week 6 and 1 year in the fat beverage (FAT-BEV) group compared with baseline. PYY AUC remained elevated at 1 year in the FAT-BEV group. Ghrelin AUC decreased at week 2, week 6, and 1 year in the protein beverage (PRO-BEV) group compared with baseline. Ghrelin AUC was lower in the PRO-BEV group compared with the FAT-BEV group at week 6. Fasted leptin decreased at all visits in both groups and was lower in the FAT-BEV group compared with the PRO-BEV group at 1 year. CONCLUSIONS Changes from baseline were evident for all GI hormones and leptin; some differences were evident soon after surgery (ghrelin, leptin), whereas others were maintained long term (GLP-1, PYY, ghrelin, leptin). In response to a short-term stimulus, protein suppressed ghrelin and fat potently stimulated GLP-1 and PYY. Future work in this area is warranted.
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Affiliation(s)
- Lauren M. Beckman
- Department of Food Science and Nutrition, University of Minnesota, Minneapolis, Minnesota
| | | | | | - William Thomas
- School of Public Health, University of Minnesota, Minneapolis, Minnesota
| | - Sayeed Ikramuddin
- Department of Surgery, University of Minnesota, Minneapolis, Minnesota
| | - Todd A. Kellogg
- Department of Surgery, University of Minnesota, Minneapolis, Minnesota
| | - Mohammad A. Ghatei
- Department of Investigative Medicine, Imperial College London, London, United Kingdom
| | - Stephen R. Bloom
- Department of Investigative Medicine, Imperial College London, London, United Kingdom
| | - Carel W. le Roux
- Department of Investigative Medicine, Imperial College London, London, United Kingdom
| | - Carrie P. Earthman
- Department of Food Science and Nutrition, University of Minnesota, Minneapolis, Minnesota
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Granado-Lorencio F, Simal-Antón A, Salazar-Mosteiro J, Herrero-Barbudo C, Donoso-Navarro E, Blanco-Navarro I, Pérez-Sacristán B. Time-course changes in bone turnover markers and fat-soluble vitamins after obesity surgery. Obes Surg 2011; 20:1524-9. [PMID: 20740379 DOI: 10.1007/s11695-010-0257-1] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
BACKGROUND The available evidence indicates a progressive increase in the incidence and severity of the deficiency of certain vitamins and related clinical conditions (i.e., metabolic bone disease). Because of the potential role of fat-soluble vitamins and carotenoids in bone metabolism, our aim was to assess the time-course changes of fat-soluble vitamins and serum markers of bone metabolism in candidates for obesity surgery and following two bariatric procedures. METHODS Sixty-five candidates for bariatric surgery and 150 serum samples after obesity surgery (i.e., Roux-en-Y gastric bypass, n = 85; biliopancreatic diversion, n = 65) were consecutively analyzed over a period of more than 2 years. Retinol, α- and γ-tocopherol, 25-OH-vitamin D3, β-cryptoxanthin, and β-carotene were analyzed by high-performance liquid chromatography. Calcium, phosphorus, alkaline phosphatase, intact parathyroid hormone (iPTH), osteocalcin, beta-crosslaps, and N-terminal peptide of procollagen I (P1NP) were determined using commercial kits. RESULTS Retinol, β-cryptoxanthin, β-carotene, and α- and γ-tocopherol levels were significantly lower in post-surgery samples while osteocalcin, b-crosslaps, and P1NP were significantly increased. Along the time and regardless of the surgical procedure, P1NP, b-crosslaps, and osteocalcin increased during the first 12-24 months but declined afterward. 25-OH-vitamin D increased during the first 12 months and tended to decrease afterward while iPTH remained constant or decreased but increased after 1 year in both groups. Vitamin A remained constant but α- and γ-tocopherol, β-cryptoxanthin, and β-carotene decreased in both groups. CONCLUSIONS In addition to the nutritional assessment, regular monitoring of bone markers seems necessary in these patients and the early introduction of preventive strategies (i.e., the use of antiresorptive agents) should be evaluated.
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Vila G, Riedl M, Anderwald C, Resl M, Handisurya A, Clodi M, Prager G, Ludvik B, Krebs M, Luger A. The relationship between insulin resistance and the cardiovascular biomarker growth differentiation factor-15 in obese patients. Clin Chem 2010; 57:309-16. [PMID: 21164037 DOI: 10.1373/clinchem.2010.153726] [Citation(s) in RCA: 141] [Impact Index Per Article: 9.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
BACKGROUND Growth differentiation factor-15 (GDF-15) is a stress-responsive cytokine linked to obesity comorbidities such as cardiovascular disease, inflammation, and cancer. GDF-15 also has adipokine properties and recently emerged as a prognostic biomarker for cardiovascular events. METHODS We evaluated the relationship of plasma GDF-15 concentrations with parameters of obesity, inflammation, and glucose and lipid metabolism in a cohort of 118 morbidly obese patients [mean (SD) age 37.2 (12) years, 89 females, 29 males] and 30 age- and sex-matched healthy lean individuals. All study participants underwent a 75-g oral glucose tolerance test; 28 patients were studied before and 1 year after Roux-en-Y gastric bypass surgery. RESULTS Obese individuals displayed increased plasma GDF-15 concentrations (P < 0.001), with highest concentrations observed in patients with type 2 diabetes. GDF-15 was positively correlated with age, waist-to-height ratio, mean arterial blood pressure, triglycerides, creatinine, glucose, insulin, C-peptide, hemoglobin A(1c), and homeostatic model assessment insulin resistance index and negatively correlated with oral glucose insulin sensitivity. Age, homeostatic model assessment index, oral glucose insulin sensitivity, and creatinine were independent predictors of GDF-15 concentrations. Roux-en-Y gastric bypass led to a significant reduction in weight, leptin, insulin, and insulin resistance, but further increased GDF-15 concentrations (P < 0.001). CONCLUSIONS The associations between circulating GDF-15 concentrations and age, insulin resistance, and creatinine might account for the additional cardiovascular predictive information of GDF-15 compared to traditional risk factors. Nevertheless, GDF-15 changes following bariatric surgery suggest an indirect relationship between GDF-15 and insulin resistance. The clinical utility of GDF-15 as a biomarker might be limited until the pathways directly controlling GDF-15 concentrations are better understood.
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Affiliation(s)
- Greisa Vila
- Division of Endocrinology and Metabolism, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
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Harvey EJ, Arroyo K, Korner J, Inabnet WB. Hormone Changes Affecting Energy Homeostasis after Metabolic Surgery. ACTA ACUST UNITED AC 2010; 77:446-65. [DOI: 10.1002/msj.20203] [Citation(s) in RCA: 48] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
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[Abnormalities of bone metabolism in bariatric surgery]. Med Clin (Barc) 2010; 136:215-21. [PMID: 20417940 DOI: 10.1016/j.medcli.2009.12.020] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2009] [Revised: 12/09/2009] [Accepted: 12/15/2009] [Indexed: 02/06/2023]
Abstract
Obesity is an ever-increasing disease in our environment, and a major risk factor for the development of other chronic diseases that increase morbidity and mortality. Bariatric surgery is an effective treatment for obesity, since it not only allows a significant and sustained loss of weight, but also an important reduction of its co-morbidities. However, this treatment is not free of complications, since along with weight loss, frequent nutritional and metabolic deficiencies have been described. These complications are particularly frequent when mixed surgical procedures with a restrictive and malabsortive component such as Roux-en-Y gastric bypass and biliopancreatic diversion are performed. The nutritional deficiencies observed include, to a greater or lesser extent, malabsorption of fat and liposoluble vitamins, as well as other micronutrients such as calcium. As a result, disorders of bone mineral metabolism with skeletal manifestations that include bone mass reduction, increased bone turnover and defective bone mineralization may develop.
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Beckman LM, Beckman TR, Earthman CP. Changes in gastrointestinal hormones and leptin after Roux-en-Y gastric bypass procedure: a review. ACTA ACUST UNITED AC 2010; 110:571-84. [PMID: 20338283 DOI: 10.1016/j.jada.2009.12.023] [Citation(s) in RCA: 136] [Impact Index Per Article: 9.1] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2009] [Accepted: 06/08/2009] [Indexed: 12/25/2022]
Abstract
Roux-en-Y gastric bypass is a well-accepted tool for the treatment of obesity and, compared to conventional weight loss methods (eg, diet and exercise) and other weight loss surgeries (eg, gastric banding), it results in considerable weight loss that is maintained long term. Although successful, the mechanisms for weight loss are not completely understood and it is thought that gastrointestinal hormones play a role. Several gastrointestinal hormones have been identified for their effects on appetite, including glucagon-like peptide-1 (GLP-1), peptide tyrosine-tyrosine (PYY), leptin, and ghrelin. This review encompasses a literature search that included 45 primary articles and shows that there are alterations in GLP-1, PYY, leptin, and ghrelin postoperatively. GLP-1 and PYY concentrations were usually found to be higher, whereas ghrelin levels were typically lower post- Roux-en-Y gastric bypass than in individuals with obesity, those who were overweight or of normal weight, and in those who underwent procedures other than Roux-en-Y gastric bypass or who achieved weight loss by lifestyle modification. An understanding of how gastrointestinal hormones change after Roux-en-Y gastric bypass may help dietetics practitioners optimize nutrition care for this patient population. A review of the literature also highlighted some research gaps that should be taken into consideration when designing future studies.
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Affiliation(s)
- Lauren M Beckman
- Department of Food Science and Nutrition, University of Minnesota, 225 Food Science and Nutrition, University of Minnesota, 1334 Eckles Ave, St Paul, MN 55108-6099, USA
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Georgiadou P, Iliodromitis EK, Kolokathis F, Varounis C, Gizas V, Mavroidis M, Capetanaki Y, Boudoulas H, Kremastinos DT. Osteopontin as a novel prognostic marker in stable ischaemic heart disease: a 3-year follow-up study. Eur J Clin Invest 2010; 40:288-93. [PMID: 20192976 DOI: 10.1111/j.1365-2362.2010.02257.x] [Citation(s) in RCA: 37] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
Abstract
OBJECTIVES Osteopontin (OPN) is a glycoprotein, which may play a major role in the regulation of biological phenomena. Increased levels of OPN have been linked to the presence and to the severity of atherosclerosis. This study was undertaken to assess the prognostic significance of plasma OPN levels in patients with stable ischaemic heart disease (IHD). METHODS In 101 patients with stable IHD and angiographically documented significant coronary artery stenosis, plasma OPN levels were measured at baseline (time of coronary arteriography). Patients were prospectively followed for a median time of 3 years (minimum 2.25, maximum 3.9 years). The primary study endpoint was the composite of cardiovascular death, non-fatal myocardial infarction, need for revascularization and hospitalization for cardiovascular reasons. RESULTS Baseline lnOPN levels were directly related to age (r = 0.27, P < 0.001) and inversely to left ventricular ejection fraction (r = -0.32, P < 0.01). Left ventricular ejection fraction was an independent predictor of plasma OPN levels after adjustment for age and gender (beta = -0.013, P = 0.02). Median OPN value was 55 ng mL(-1). In the univariate Cox-regression analysis, OPN levels > 55 ng mL(-1) (n = 50) were significantly related to adverse cardiac outcome (HR = 2.40, 95% CI: 1.11-5.23, P = 0.027). In multivariate model, OPN levels > 55 ng mL(-1) remained statistically significant independent predictor of adverse outcome after adjustment for age, gender, left ventricular ejection fraction and the number of diseased coronary arteries (HR = 2.88, 95% CI: 1.09-7.58, P = 0.032). CONCLUSION OPN may provide significant prognostic information independent of other traditional prognostic markers in patients with stable IHD.
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Kiefer FW, Zeyda M, Gollinger K, Pfau B, Neuhofer A, Weichhart T, Säemann MD, Geyeregger R, Schlederer M, Kenner L, Stulnig TM. Neutralization of osteopontin inhibits obesity-induced inflammation and insulin resistance. Diabetes 2010; 59:935-46. [PMID: 20107108 PMCID: PMC2844841 DOI: 10.2337/db09-0404] [Citation(s) in RCA: 156] [Impact Index Per Article: 10.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
OBJECTIVE Obesity is associated with a state of chronic low-grade inflammation mediated by immune cells that are primarily located to adipose tissue and liver. The chronic inflammatory response appears to underlie obesity-induced metabolic deterioration including insulin resistance and type 2 diabetes. Osteopontin (OPN) is an inflammatory cytokine, the expression of which is strongly upregulated in adipose tissue and liver upon obesity. Here, we studied OPN effects in obesity-induced inflammation and insulin resistance by targeting OPN action in vivo. RESEARCH DESIGN AND METHODS C57BL/6J mice were fed a high-fat diet to induce obesity and were then intravenously treated with an OPN-neutralizing or control antibody. Insulin sensitivity and inflammatory alterations in adipose tissue and liver were assessed. RESULTS Interference with OPN action by a neutralizing antibody for 5 days significantly improved insulin sensitivity in diet-induced obese mice. Anti-OPN treatment attenuated liver and adipose tissue macrophage infiltration and inflammatory gene expression by increasing macrophage apoptosis and significantly reducing c-Jun NH(2)-terminal kinase activation. Moreover, we report OPN as a novel negative regulator for the activation of hepatic signal transducer and activator of transcription 3 (STAT3), which is essential for glucose homeostasis and insulin sensitivity. Consequently, OPN neutralization decreased expression of hepatic gluconeogenic markers, which are targets of STAT3-mediated downregulation. CONCLUSIONS These findings demonstrate that antibody-mediated neutralization of OPN action significantly reduces insulin resistance in obesity. OPN neutralization partially decreases obesity-associated inflammation in adipose tissue and liver and reverses signal transduction related to insulin resistance and glucose homeostasis. Hence, targeting OPN could provide a novel approach for the treatment of obesity-related metabolic disorders.
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Affiliation(s)
- Florian W. Kiefer
- Clinical Division of Endocrinology and Metabolism, Department of Medicine III, Medical University of Vienna, Vienna, Austria
| | - Maximilian Zeyda
- Clinical Division of Endocrinology and Metabolism, Department of Medicine III, Medical University of Vienna, Vienna, Austria
| | - Karina Gollinger
- Clinical Division of Endocrinology and Metabolism, Department of Medicine III, Medical University of Vienna, Vienna, Austria
| | - Birgit Pfau
- Clinical Division of Endocrinology and Metabolism, Department of Medicine III, Medical University of Vienna, Vienna, Austria
| | - Angelika Neuhofer
- Clinical Division of Endocrinology and Metabolism, Department of Medicine III, Medical University of Vienna, Vienna, Austria
| | - Thomas Weichhart
- Clinical Division of Nephrology and Dialysis, Department of Medicine III, Medical University of Vienna, Vienna, Austria
| | - Marcus D. Säemann
- Clinical Division of Nephrology and Dialysis, Department of Medicine III, Medical University of Vienna, Vienna, Austria
| | - René Geyeregger
- Clinical Division of Endocrinology and Metabolism, Department of Medicine III, Medical University of Vienna, Vienna, Austria
| | - Michaela Schlederer
- Ludwig Boltzmann Institute for Cancer Research, Medical University of Vienna, Vienna, Austria
| | - Lukas Kenner
- Ludwig Boltzmann Institute for Cancer Research, Medical University of Vienna, Vienna, Austria
- Department of Pathology, Medical University of Vienna, Vienna, Austria
| | - Thomas M. Stulnig
- Clinical Division of Endocrinology and Metabolism, Department of Medicine III, Medical University of Vienna, Vienna, Austria
- Corresponding author: Thomas M. Stulnig,
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Winhofer Y, Handisurya A, Tura A, Bittighofer C, Klein K, Schneider B, Bieglmayer C, Wagner OF, Pacini G, Luger A, Kautzky-Willer A. Osteocalcin is related to enhanced insulin secretion in gestational diabetes mellitus. Diabetes Care 2010; 33:139-43. [PMID: 19808925 PMCID: PMC2797959 DOI: 10.2337/dc09-1237] [Citation(s) in RCA: 55] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
Abstract
OBJECTIVE There is growing evidence that osteocalcin, an osteoblast-derived protein locally acting on bone formation, can increase insulin secretion as well as insulin sensitivity and thus prevent the development of obesity and diabetes in experimental animals. In humans, osteocalcin has been reported to be decreased in patients with type 2 diabetes. Because gestational diabetes mellitus (GDM) can serve as a model of pre-type 2 diabetes, the aim of this study was to investigate osteocalcin in GDM. RESEARCH DESIGN AND METHODS Osteocalcin measurement and an oral glucose tolerance test were performed in 78 pregnant women (26 women had GDM and 52 women had normal glucose tolerance [NGT] during pregnancy; women were matched for age and BMI) and in 34 women postpartum. RESULTS During pregnancy osteocalcin was significantly higher in the women with GDM than in the women with NGT (15.6 +/- 6.4 vs. 12.6 +/- 4.0 ng/ml; P < 0.015), whereas no difference was observed between the two groups at 12 weeks postpartum (36.2 +/- 10.2 vs. 36.2 +/- 13.0 ng/ml), when osteocalcin was found to be increased compared with the level in the pregnant state in all women (+145 +/- 102% in GDM vs. +187 +/- 119% in NGT; P < 0.0001). Moreover, osteocalcin showed a significant correlation with basal and total insulin secretion in the whole study group (R = 0.3, P < 0.01). CONCLUSIONS In GDM osteocalcin was higher and thus less restrained than in women with NGT during pregnancy and furthermore correlated with insulin secretion parameters. Therefore, it could be hypothesized that osteocalcin can enhance insulin secretion in insulin-resistant states; alternatively an effect of hyperinsulinemia on osteocalcin secretion cannot be excluded.
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Affiliation(s)
- Yvonne Winhofer
- Department of Internal Medicine III, Division of Endocrinology and Metabolism, Medical University of Vienna, Vienna, Austria
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