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Ratajczak-Pawłowska AE, Szymczak-Tomczak A, Hryhorowicz S, Zawada A, Skoracka K, Rychter AM, Skrzypczak-Zielińska M, Słomski R, Dobrowolska A, Krela-Kaźmierczak I. Relationship of visfatin with obesity and osteoporosis in patients with inflammatory bowel disease: a narrative review. Front Immunol 2025; 16:1533955. [PMID: 40170859 PMCID: PMC11959099 DOI: 10.3389/fimmu.2025.1533955] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2024] [Accepted: 02/21/2025] [Indexed: 04/03/2025] Open
Abstract
Background Inflammatory bowel disease (IBD) is an increasingly prevalent condition in developed countries. Alongside the growing number of patients, there is a rising incidence of disease-related complications, including osteoporosis. While well-established risk factors for low bone mineral density in IBD-such as low body mass or steroid therapy-are widely recognized, other contributing factors warrant further investigation. One such factor is visfatin, a proinflammatory adipokine encoded by the NAMPT gene. Objectives This review aimed to explore the association between visfatin level, bone health, and obesity among patients with inflammatory bowel disease. Key findings Although visfatin is primarily associated with metabolic syndrome, it may also influence bone mineral density by affecting osteoblast and osteoclast differentiation and function. Additionally, some studies have identified a correlation between visfatin levels and bone mineral density. A deeper understanding of visfatin's role in osteoporosis development may contribute to the identification of novel therapeutic strategies. Therefore, lower bone mineral density in inflammatory bowel disease may be associated with obesity and visfatin levels. However, visfatin concentrations depend on many factors, including genetics, immunology, and nutritional factors, which may affect visfatin levels. Implications Current research highlights visfatin as both a potential biomarker and a therapeutic target for osteoporosis treatment. Nevertheless, limited studies have specifically examined the relationship between visfatin and bone mineral density in IBD. Further research is required to clarify this association and to explore how variations in visfatin levels impact bone density in IBD patients.
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Affiliation(s)
- Alicja Ewa Ratajczak-Pawłowska
- Department of Gastroenterology, Dietetics and Internal Diseases, Poznan University of Medical Sciences, Poznan, Poland
- Laboratory of Nutrigenetics, Department of Gastroenterology, Dietetics and Internal Diseases, Poznan University of Medical Sciences, Poznan, Poland
| | - Aleksandra Szymczak-Tomczak
- Department of Gastroenterology, Dietetics and Internal Diseases, Poznan University of Medical Sciences, Poznan, Poland
| | - Szymon Hryhorowicz
- Institute of Human Genetics, Polish Academy of Sciences Poznan, Poznan, Poland
| | - Agnieszka Zawada
- Department of Gastroenterology, Dietetics and Internal Diseases, Poznan University of Medical Sciences, Poznan, Poland
| | - Kinga Skoracka
- Department of Gastroenterology, Dietetics and Internal Diseases, Poznan University of Medical Sciences, Poznan, Poland
- Doctoral School, Poznan University of Medical Sciences, Poznan, Poland
| | - Anna Maria Rychter
- Department of Gastroenterology, Dietetics and Internal Diseases, Poznan University of Medical Sciences, Poznan, Poland
- Laboratory of Nutrigenetics, Department of Gastroenterology, Dietetics and Internal Diseases, Poznan University of Medical Sciences, Poznan, Poland
| | | | - Ryszard Słomski
- Institute of Medical Sciences, College of Social and Media Culture in Torun, Torun, Poland
- Laboratory of Molecular Genetics, Poznan, Poland
| | - Agnieszka Dobrowolska
- Department of Gastroenterology, Dietetics and Internal Diseases, Poznan University of Medical Sciences, Poznan, Poland
| | - Iwona Krela-Kaźmierczak
- Department of Gastroenterology, Dietetics and Internal Diseases, Poznan University of Medical Sciences, Poznan, Poland
- Laboratory of Nutrigenetics, Department of Gastroenterology, Dietetics and Internal Diseases, Poznan University of Medical Sciences, Poznan, Poland
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Duan F, Wu J, Chang J, Peng H, Liu Z, Liu P, Han X, Sun T, Shang D, Yang Y, Li Z, Li P, Liu Y, Zhu Y, Lv Y, Guo X, Zhao Y, An Y. Deciphering endocrine function of adipose tissue and its significant influences in obesity-related diseases caused by its dysfunction. Differentiation 2025; 141:100832. [PMID: 39709882 DOI: 10.1016/j.diff.2024.100832] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2024] [Revised: 12/15/2024] [Accepted: 12/16/2024] [Indexed: 12/24/2024]
Abstract
Current research has found that adipose tissue is not only involved in energy metabolism, but also a highly active endocrine organ that secretes various adipokines, including adiponectin, leptin, resistin and apelin, which are involved in the regulation of physiology and pathology of tissues and organs throughout the body. With the yearly increasing incidence, obesity has become a risk factor for a variety of pathological changes, including inflammation and metabolic syndrome in various system (endocrine, circulatory, locomotor and central nervous system). Thus these symptoms lead to multi-organ dysfunctions, including the heart, liver, kidneys, brain and joints. An in-depth summary of the roles of adipokines in the regulation of other tissues and organs can help to provide more effective therapeutic strategies for obesity-related diseases and explore potential therapeutic targets. Therefore, this review has retrospected the endocrine function of adipose tissue under obesity and the role of dysregulated adipokine secretion in related diseases and the underlying mechanisms, in order to provide a theoretical basis for targeting adipokine-mediated systemic dysregulation.
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Affiliation(s)
- Feiyi Duan
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Henan University, Kaifeng, 475004, China; Henan Provincial Engineering Center for Tumor Molecular Medicine, Kaifeng Key Laboratory of Cell Signal Transduction, Henan University, Kaifeng, 475004, China
| | - Jiaoyan Wu
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Henan University, Kaifeng, 475004, China; Henan Provincial Engineering Center for Tumor Molecular Medicine, Kaifeng Key Laboratory of Cell Signal Transduction, Henan University, Kaifeng, 475004, China
| | - Jiayi Chang
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Henan University, Kaifeng, 475004, China; Henan Provincial Engineering Center for Tumor Molecular Medicine, Kaifeng Key Laboratory of Cell Signal Transduction, Henan University, Kaifeng, 475004, China
| | - Haoyuan Peng
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Henan University, Kaifeng, 475004, China; Henan Provincial Engineering Center for Tumor Molecular Medicine, Kaifeng Key Laboratory of Cell Signal Transduction, Henan University, Kaifeng, 475004, China
| | - Zitao Liu
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Henan University, Kaifeng, 475004, China; Henan Provincial Engineering Center for Tumor Molecular Medicine, Kaifeng Key Laboratory of Cell Signal Transduction, Henan University, Kaifeng, 475004, China
| | - Pengfei Liu
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Henan University, Kaifeng, 475004, China; Henan Provincial Engineering Center for Tumor Molecular Medicine, Kaifeng Key Laboratory of Cell Signal Transduction, Henan University, Kaifeng, 475004, China
| | - Xu Han
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Henan University, Kaifeng, 475004, China; School of Stomatology, Henan University, Kaifeng, 475004, China
| | - Tiantian Sun
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Henan University, Kaifeng, 475004, China; School of Stomatology, Henan University, Kaifeng, 475004, China
| | - Dandan Shang
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Henan University, Kaifeng, 475004, China; Henan Provincial Engineering Center for Tumor Molecular Medicine, Kaifeng Key Laboratory of Cell Signal Transduction, Henan University, Kaifeng, 475004, China
| | - Yutian Yang
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Henan University, Kaifeng, 475004, China; Henan Provincial Engineering Center for Tumor Molecular Medicine, Kaifeng Key Laboratory of Cell Signal Transduction, Henan University, Kaifeng, 475004, China
| | - Zhihao Li
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Henan University, Kaifeng, 475004, China; Henan Provincial Engineering Center for Tumor Molecular Medicine, Kaifeng Key Laboratory of Cell Signal Transduction, Henan University, Kaifeng, 475004, China
| | - Pengkun Li
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Henan University, Kaifeng, 475004, China; Henan Provincial Engineering Center for Tumor Molecular Medicine, Kaifeng Key Laboratory of Cell Signal Transduction, Henan University, Kaifeng, 475004, China
| | - Yixuan Liu
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Henan University, Kaifeng, 475004, China; Henan Provincial Engineering Center for Tumor Molecular Medicine, Kaifeng Key Laboratory of Cell Signal Transduction, Henan University, Kaifeng, 475004, China
| | - Yonghao Zhu
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Henan University, Kaifeng, 475004, China; School of Stomatology, Henan University, Kaifeng, 475004, China
| | - Yunzhi Lv
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Henan University, Kaifeng, 475004, China; School of Stomatology, Henan University, Kaifeng, 475004, China
| | - Xiumei Guo
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Henan University, Kaifeng, 475004, China; Henan Provincial Engineering Center for Tumor Molecular Medicine, Kaifeng Key Laboratory of Cell Signal Transduction, Henan University, Kaifeng, 475004, China
| | - Ying Zhao
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Henan University, Kaifeng, 475004, China; Henan Provincial Engineering Center for Tumor Molecular Medicine, Kaifeng Key Laboratory of Cell Signal Transduction, Henan University, Kaifeng, 475004, China
| | - Yang An
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Henan University, Kaifeng, 475004, China; Henan Provincial Engineering Center for Tumor Molecular Medicine, Kaifeng Key Laboratory of Cell Signal Transduction, Henan University, Kaifeng, 475004, China.
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Wu Y, Shen J. Unraveling the intricacies of neutrophil extracellular traps in inflammatory bowel disease: Pathways, biomarkers, and promising therapies. Cytokine Growth Factor Rev 2024; 80:156-167. [PMID: 39438227 DOI: 10.1016/j.cytogfr.2024.10.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2024] [Accepted: 10/06/2024] [Indexed: 10/25/2024]
Abstract
The development of inflammatory bowel disease (IBD), including ulcerative colitis and Crohn's disease, involves various factors and is characterized by persistent inflammation of the mucosal lining. However, the role of neutrophils in this process remains controversial. Neutrophil extracellular traps (NETs), which consist of chromatin, antimicrobial proteins, and oxidative enzymes, are released by neutrophils to trap pathogens. They are also involved in various immune-mediated and vascular diseases. NETs act as a vital defense mechanisms at the gut-mucosal interface and are frequently exposed to bacterial, viral, and fungal threats. However, they can also contribute to inflammation and worsen imbalances in the gut bacteria. Recent studies have suggested that NETs have a significant impact on IBD development. Previous studies have shown increased levels of NETs in tissue and blood samples from patients with IBD, as well as in experimental colitis mouse models. Therefore, this review discusses how NETs are formed and their role in the pathophysiology of IBD. It discusses how NETs may lead to tissue damage and contribute to IBD-associated complications. Moreover, non-invasive biomarkers are needed to replace invasive procedures such as endoscopy to better evaluate the disease status. Given the crucial role of NETs in IBD progression, this review focuses on potential NET biomarkers that can help predict the evolution of IBD. Furthermore, this review identifies potential therapeutic targets for regulating NET production, which could expand the range of available treatment options for IBD.
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Affiliation(s)
- Yilin Wu
- Division of Gastroenterology and Hepatology, Baoshan Branch, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China; Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Inflammatory Bowel Disease Research Center, Shanghai 200127, China; Renji Hospital, School of Medicine, Shanghai Jiao Tong University, China; Shanghai Institute of Digestive Disease, No.160 PuJian Road, China
| | - Jun Shen
- Division of Gastroenterology and Hepatology, Baoshan Branch, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China; Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Inflammatory Bowel Disease Research Center, Shanghai 200127, China; Renji Hospital, School of Medicine, Shanghai Jiao Tong University, China; Shanghai Institute of Digestive Disease, No.160 PuJian Road, China.
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Geryk M, Kucerova V, Velganova-Veghova M, Foltenova H, Bouchalova K, Karasek D, Radvansky M, Karaskova E. Association of selected adipokines with vitamin D deficiency in children with inflammatory bowel disease. BMC Pediatr 2024; 24:426. [PMID: 38961351 PMCID: PMC11223338 DOI: 10.1186/s12887-024-04890-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/20/2023] [Accepted: 06/19/2024] [Indexed: 07/05/2024] Open
Abstract
BACKGROUND Adipose tissue is significantly involved in inflammatory bowel disease (IBD). Vitamin D can affect both adipogenesis and inflammation. The aim of this study was to compare the production of selected adipokines, potentially involved in the pathogenesis of IBD - adiponectin, resistin, retinol binding protein 4 (RBP-4), adipocyte fatty acid binding protein and nesfatin-1 in children with IBD according to the presence of 25-hydroxyvitamin D (25(OH)D) deficiency. METHODS The study was conducted as a case-control study in pediatric patients with IBD and healthy children of the same sex and age. In addition to adipokines and 25(OH)D, anthropometric parameters, markers of inflammation and disease activity were assessed in all participants. RESULTS Children with IBD had significantly higher resistin levels regardless of 25(OH)D levels. IBD patients with 25(OH)D deficiency only had significantly lower RBP-4 compared to healthy controls and also compared to IBD patients without 25(OH)D deficiency. No other significant differences in adipokines were found in children with IBD with or without 25(OH)D deficiency. 25(OH)D levels in IBD patients corelated with RBP-4 only, and did not correlate with other adipokines. CONCLUSIONS Whether the lower RBP-4 levels in the 25(OH)D-deficient group of IBD patients directly reflect vitamin D deficiency remains uncertain. The production of other adipokines does not appear to be directly related to vitamin D deficiency.
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Affiliation(s)
- Milos Geryk
- Department of Pediatrics, University Hospital Olomouc, Faculty of Medicine and Dentistry Palacky University Olomouc, Olomouc, Czech Republic
| | - Veronika Kucerova
- Department of Clinical Biochemistry, University Hospital Olomouc, Olomouc, Czech Republic
| | - Maria Velganova-Veghova
- Department of Pediatrics, University Hospital Olomouc, Faculty of Medicine and Dentistry Palacky University Olomouc, Olomouc, Czech Republic
| | - Hana Foltenova
- Department of Pediatrics, University Hospital Olomouc, Faculty of Medicine and Dentistry Palacky University Olomouc, Olomouc, Czech Republic
| | - Katerina Bouchalova
- Department of Pediatrics, University Hospital Olomouc, Faculty of Medicine and Dentistry Palacky University Olomouc, Olomouc, Czech Republic
| | - David Karasek
- 3rd Department of Internal Medicine - Nephrology, Rheumatology and Endocrinology, University Hospital Olomouc, Faculty of Medicine and Dentistry, Palacky University Olomouc, Olomouc, Czech Republic
| | - Martin Radvansky
- Department of Computer Science, Faculty of Electrical Engineering and Computer Science, VSB-Technical University of Ostrava, Ostrava - Poruba, Czech Republic
| | - Eva Karaskova
- Department of Pediatrics, University Hospital Olomouc, Faculty of Medicine and Dentistry Palacky University Olomouc, Olomouc, Czech Republic.
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Behnoush AH, Maroufi SP, Reshadmanesh T, Mohtasham Kia Y, Norouzi M, Mohammadi SM, Klisic A, Khalaji A. Circulatory resistin levels in inflammatory bowel disease: a systematic review and meta-analysis. BMC Gastroenterol 2024; 24:107. [PMID: 38486190 PMCID: PMC10941394 DOI: 10.1186/s12876-024-03199-7] [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: 11/14/2023] [Accepted: 03/11/2024] [Indexed: 03/17/2024] Open
Abstract
BACKGROUND Inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn's disease (CD), is a chronic relapsing-remitting systemic disease of the gastrointestinal tract with rising incidence. Studies have shown that adipocytes play a crucial role in patients with IBD by actively participating in systemic immune responses. The present study was designed to investigate the correlation between the circulatory levels of resistin, as an adipokine, and active and remission phases of IBD in comparison with healthy controls. METHODS Relevant articles were retrieved from PubMed, Embase, the Web of Science, and Scopus from inception until June 2023. Estimation of the standardized mean difference (SMD) and 95% confidence interval (CI) for comparison of plasma/serum resistin levels between IBD patients, patients in remission, and healthy controls were conducted through random-effect meta-analysis. RESULTS A total of 19 studies were included, assessing 1836 cases. Meta-analysis indicated that generally, serum/plasma resistin levels were higher in IBD patients in comparison with healthy controls (SMD 1.33, 95% CI 0.58 to 2.08, p-value < 0.01). This was true for each of the UC and CD separate analyses, as well. Moreover, it was shown that higher serum/plasma resistin levels were detected in the active phase of IBD than in the remission phase (SMD 1.04, 95% CI 0.65 to 1.42, p-value = 0.01). Finally, higher serum/plasma resistin levels were found in the remission phase compared to healthy controls (SMD 0.60, 95% CI 0.15 to 1.06, p-value < 0.01). CONCLUSION The results of this systematic review and meta-analysis support the conclusion that circulating resistin levels are increased in IBD (both UC and CD). Also, higher resistin levels were recorded in the remission phase of IBD in comparison with healthy controls. This indicates that further studies may provide valuable insights into the role of resistin in the pathogenesis of IBD.
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Affiliation(s)
- Amir Hossein Behnoush
- School of Medicine, Tehran University of Medical Sciences, Poursina St., Keshavarz Blvd, 1417613151, Tehran, Iran.
- Non-Communicable Diseases Research Center, Endocrinology and Metabolism Population Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran.
| | - Seyede Parmis Maroufi
- Neurosurgical Research Network, Universal Scientific Education and Research Network, Tehran University of Medical Sciences, Tehran, Iran
| | - Tara Reshadmanesh
- Student Research Center, School of Medicine, Zanjan University of Medical Science, Zanjan, Iran
| | | | - Mitra Norouzi
- Faculty of Life Sciences and Biotechnology, Shahid Beheshti University, Tehran, Iran
| | | | - Aleksandra Klisic
- Faculty of Medicine, University of Montenegro, Podgorica, Montenegro
- Center for Laboratory Diagnostics, Primary Health Care Center, Podgorica, Montenegro
| | - Amirmohammad Khalaji
- School of Medicine, Tehran University of Medical Sciences, Poursina St., Keshavarz Blvd, 1417613151, Tehran, Iran
- Non-Communicable Diseases Research Center, Endocrinology and Metabolism Population Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
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Fryk E, Wilsson Å, Tompa A, Jansson PA, Faresjö M. Galectin-1 correlates with inflammatory markers and T regulatory cells in children with type 1 diabetes and/or celiac disease. Clin Exp Immunol 2024; 215:240-250. [PMID: 38088456 PMCID: PMC10876110 DOI: 10.1093/cei/uxad131] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2023] [Revised: 11/01/2023] [Accepted: 12/05/2023] [Indexed: 02/20/2024] Open
Abstract
Type 1 diabetes (T1D) and celiac disease (CeD) are common autoimmune diseases in children where the pathophysiology is not fully characterized. The autoimmune process involves a complex scenario of both inflammatory and regulatory features. Galectin-1 (GAL-1) has a wide range of biological activities e.g. interaction with immune cells. We examined the relationship between GAL-1 and soluble immune markers and T-cell subsets in a cohort of children with T1D and/or CeD relative to healthy children. GAL-1, together with several soluble immune markers [e.g. interleukins (IL)], tumor necrosis factor (TNF), acute phase proteins, and matrix metalloproteinases (MMP) were measured in sera from children with T1D and/or CeD by fluorochrome (Luminex) technique using children without these diseases as a reference. Subgroups of T cells, including T-regulatory (Treg) cells, were analysed by flow cytometry. Association between GAL-1, pro-inflammatory markers, and Treg cells differed depending on which illness combination was present. In children with both T1D and CeD, GAL-1 correlated positively with pro-inflammatory markers (IL-1β, IL-6, and TNF-α). Composite scores increased the strength of correlation between GAL-1 and pro-inflammatory markers, Th1-associated interferon (IFN)-γ, and T1D-associated visfatin. Contrary, in children diagnosed with exclusively T1D, GAL-1 was positively correlated to CD25hi and CD25hiCD101+ Treg cells. For children with only CeD, no association between GAL-1 and other immune markers was observed. In conclusion, the association observed between GAL-1, soluble immune markers, and Treg cells may indicate a role for GAL-1 in the pathophysiology of T1D and, to some extent, also in CeD.
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Affiliation(s)
- Emanuel Fryk
- Wallenberg Laboratory, Department of Molecular and Clinical Medicine, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden
| | - Åsa Wilsson
- Department of Natural Science and Biomedicine, School of Health and Welfare, Jönköping University, Jönköping, Sweden
| | - Andrea Tompa
- Department of Natural Science and Biomedicine, School of Health and Welfare, Jönköping University, Jönköping, Sweden
- Division of Medical Diagnostics, Department of Laboratory Medicine, Region Jönköping County, Sweden
| | - Per-Anders Jansson
- Wallenberg Laboratory, Department of Molecular and Clinical Medicine, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden
| | - Maria Faresjö
- Department of Life Sciences, Division of Systems and Synthetic Biology, Chalmers University of Technology, Gothenburg, Sweden
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Zheng Y, Lin J, Zhou S, Liao S, Fu Y, Zhang Y, Chen X, Li J, Sha W, Dai S, Ma W. Circulating leptin levels in the assessment of Crohn's disease activity and its relation to nutritional status. NUTR HOSP 2024; 41:130-137. [PMID: 37534522 DOI: 10.20960/nh.04572] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/04/2023] Open
Abstract
Introduction Objective: to evaluate leptin levels and its relation to nutritional status in Crohn's disease (CD). Methods: the study included 154 CD patients and healthy controls. Leptin level was determined before treatment. Nutrition levels were assessed using the Nutrition Risk Screening 2002 (NRS-2002) and Patient-Generated Subjective Global Assessment (PG-SGA). Indicators included body mass index (BMI), mid-arm circumference, the circumference of the upper-arm muscle, triceps skinfold thickness, and circumference of legs. Results: leptin levels differed between CD patients (1,025 ± 874 ng/ml) and controls (18,481,222 ng/ml). Significant differences were seen in NRS-2002, PG-SGA scores, BMI and other nutritional indicators. Negative correlations were observed between leptin and NRS-2002, PG-SGA scores, while positive correlations were observed with other nutritional indicators. The receiver operating characteristic (ROC) curve showed association between leptin and the diagnosis of CD, suggesting leptin concentration below 803.02 ng/ml as a threshold for CD. Conclusion: dysfunctional leptin regulation may relate to poor nutritional status associated with CD. The leptin level is thus an additional tool for evaluating CD patients, predicting disease activity and clinical response. Leptin may be a potential target for intervention in CD to improve nutritional status.
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Affiliation(s)
- Ying Zheng
- Department of Nutrition. Guangdong Provincial People's Hospital - Guangdong Academy of Medical Sciences. Southern Medical University
| | - Junlong Lin
- The Second School of Clinical Medicine. Southern Medical University
| | - Siqi Zhou
- The Second School of Clinical Medicine. Southern Medical University
| | - Shanying Liao
- Department of Gastroenterology. Guangdong Provincial People's Hospital - Guangdong Academy of Medical Sciences. Southern Medical University
| | - Yiming Fu
- The First School of Clinical Medicine and Nanfang Hospital. Southern Medical University
| | - Yanjun Zhang
- Department of Nutrition. Guangdong Provincial People's Hospital - Guangdong Academy of Medical Sciences. Southern Medical University
| | - Xinbin Chen
- The Second School of Clinical Medicine. Southern Medical University
| | - Jinghong Li
- The Second School of Clinical Medicine. Southern Medical University
| | - Weihong Sha
- Guangdong Provincial People's Hospital - Guangdong Academy of Medical Sciences. Southern Medical University
| | - Shixue Dai
- Department of Gastroenterology. Guangdong Provincial Geriatrics Institute. National Key Clinical Specialty. Guangdong Provincial People's Hospital - Guangdong Academy of Medical Sciences. Southern Medical University
| | - Wenjun Ma
- Department of Nutrition. Guangdong Provincial People's Hospital - Guangdong Academy of Medical Sciences. Southern Medical University
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Tsounis EP, Aggeletopoulou I, Mouzaki A, Triantos C. Creeping Fat in the Pathogenesis of Crohn's Disease: An Orchestrator or a Silent Bystander? Inflamm Bowel Dis 2023; 29:1826-1836. [PMID: 37260352 DOI: 10.1093/ibd/izad095] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/21/2022] [Indexed: 06/02/2023]
Abstract
Although the phenomenon of hypertrophied adipose tissue surrounding inflamed bowel segments in Crohn's disease has been described since 1932, the mechanisms mediating the creeping fat formation and its role in the pathogenesis of the disease have not been fully unraveled. Recent advances demonstrating the multiple actions of adipose tissue beyond energy storage have brought creeping fat to the forefront of scientific research. In Crohn's disease, dysbiosis and transmural injury compromise the integrity of the intestinal barrier, resulting in an excessive influx of intraluminal microbiota and xenobiotics. The gut and peri-intestinal fat are in close anatomic relationship, implying a direct reciprocal immunologic relationship, whereas adipocytes are equipped with an arsenal of innate immunity sensors that respond to invading stimuli. As a result, adipocytes and their progenitor cells undergo profound immunophenotypic changes, leading to adipose tissue remodeling and eventual formation of creeping fat. Indeed, creeping fat is an immunologically active organ that synthesizes various pro- and anti-inflammatory cytokines, profibrotic mediators, and adipokines that serve as paracrine/autocrine signals and regulate immune responses. Therefore, creeping fat appears to be involved in inflammatory signaling, which explains why it has been associated with a higher severity or complicated phenotype of Crohn's disease. Interestingly, there is growing evidence for an alternative immunomodulatory function of creeping fat as a second barrier that prevents an abnormal systemic inflammatory response at the expense of an increasingly proliferating profibrotic environment. Further studies are needed to clarify how this modified adipose tissue exerts its antithetic effect during the course of Crohn's disease.
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Affiliation(s)
- Efthymios P Tsounis
- Division of Gastroenterology, Department of Internal Medicine, University Hospital of Patras, Patras 26504, Greece
| | - Ioanna Aggeletopoulou
- Division of Gastroenterology, Department of Internal Medicine, University Hospital of Patras, Patras 26504, Greece
- Division of Hematology, Department of Internal Medicine, Medical School, University of Patras, Patras, Greece
| | - Athanasia Mouzaki
- Division of Hematology, Department of Internal Medicine, Medical School, University of Patras, Patras, Greece
| | - Christos Triantos
- Division of Gastroenterology, Department of Internal Medicine, University Hospital of Patras, Patras 26504, Greece
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Semerena E, Nencioni A, Masternak K. Extracellular nicotinamide phosphoribosyltransferase: role in disease pathophysiology and as a biomarker. Front Immunol 2023; 14:1268756. [PMID: 37915565 PMCID: PMC10616597 DOI: 10.3389/fimmu.2023.1268756] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2023] [Accepted: 10/03/2023] [Indexed: 11/03/2023] Open
Abstract
Nicotinamide phosphoribosyltransferase (NAMPT) plays a central role in mammalian cell metabolism by contributing to nicotinamide adenine dinucleotide biosynthesis. However, NAMPT activity is not limited to the intracellular compartment, as once secreted, the protein accomplishes diverse functions in the extracellular space. Extracellular NAMPT (eNAMPT, also called visfatin or pre-B-cell colony enhancing factor) has been shown to possess adipocytokine, pro-inflammatory, and pro-angiogenic activities. Numerous studies have reported the association between elevated levels of circulating eNAMPT and various inflammatory and metabolic disorders such as obesity, diabetes, atherosclerosis, arthritis, inflammatory bowel disease, lung injury and cancer. In this review, we summarize the current state of knowledge on eNAMPT biology, proposed roles in disease pathogenesis, and its potential as a disease biomarker. We also briefly discuss the emerging therapeutic approaches for eNAMPT inhibition.
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Affiliation(s)
- Elise Semerena
- Light Chain Bioscience - Novimmune SA, Plan-les-Ouates, Switzerland
| | - Alessio Nencioni
- Department of Internal Medicine and Medical Specialties, University of Genoa, Genoa, Italy
- Ospedale Policlinico San Martino IRCCS, Genoa, Italy
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10
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Novak EA, Crawford EC, Mentrup HL, Griffith BD, Fletcher DM, Flanagan MR, Schneider C, Firek B, Rogers MB, Morowitz MJ, Piganelli JD, Wang Q, Mollen KP. Epithelial NAD + depletion drives mitochondrial dysfunction and contributes to intestinal inflammation. Front Immunol 2023; 14:1231700. [PMID: 37744380 PMCID: PMC10512956 DOI: 10.3389/fimmu.2023.1231700] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2023] [Accepted: 08/17/2023] [Indexed: 09/26/2023] Open
Abstract
Introduction We have previously demonstrated that a pathologic downregulation of peroxisome proliferator-activated receptor-gamma coactivator 1-alpha (PGC1α) within the intestinal epithelium contributes to the pathogenesis of inflammatory bowel disease (IBD). However, the mechanism underlying downregulation of PGC1α expression and activity during IBD is not yet clear. Methods Mice (male; C57Bl/6, Villincre/+;Pgc1afl/fl mice, and Pgc1afl/fl) were subjected to experimental colitis and treated with nicotinamide riboside. Western blot, high-resolution respirometry, nicotinamide adenine dinucleotide (NAD+) quantification, and immunoprecipitation were used to in this study. Results We demonstrate a significant depletion in the NAD+ levels within the intestinal epithelium of mice undergoing experimental colitis, as well as humans with ulcerative colitis. While we found no decrease in the levels of NAD+-synthesizing enzymes within the intestinal epithelium of mice undergoing experimental colitis, we did find an increase in the mRNA level, as well as the enzymatic activity, of the NAD+-consuming enzyme poly(ADP-ribose) polymerase-1 (PARP1). Treatment of mice undergoing experimental colitis with an NAD+ precursor reduced the severity of colitis, restored mitochondrial function, and increased active PGC1α levels; however, NAD+ repletion did not benefit transgenic mice that lack PGC1α within the intestinal epithelium, suggesting that the therapeutic effects require an intact PGC1α axis. Discussion Our results emphasize the importance of PGC1α expression to both mitochondrial health and homeostasis within the intestinal epithelium and suggest a novel therapeutic approach for disease management. These findings also provide a mechanistic basis for clinical trials of nicotinamide riboside in IBD patients.
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Affiliation(s)
- Elizabeth A. Novak
- Department of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, United States
- Division of Pediatric General and Thoracic Surgery, UPMC Children’s Hospital of Pittsburgh, University of Pittsburgh Medical Center, Pittsburgh, PA, United States
| | - Erin C. Crawford
- Division of Gastroenterology, UPMC Children’s Hospital of Pittsburgh, University of Pittsburgh Medical Center, Pittsburgh, PA, United States
| | - Heather L. Mentrup
- Department of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, United States
- Division of Pediatric General and Thoracic Surgery, UPMC Children’s Hospital of Pittsburgh, University of Pittsburgh Medical Center, Pittsburgh, PA, United States
| | - Brian D. Griffith
- Department of Surgery, University of Michigan School of Medicine, Ann Arbor, MI, United States
| | - David M. Fletcher
- Division of Pediatric General and Thoracic Surgery, UPMC Children’s Hospital of Pittsburgh, University of Pittsburgh Medical Center, Pittsburgh, PA, United States
| | | | - Corinne Schneider
- Department of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, United States
- Division of Pediatric General and Thoracic Surgery, UPMC Children’s Hospital of Pittsburgh, University of Pittsburgh Medical Center, Pittsburgh, PA, United States
| | - Brian Firek
- Department of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, United States
- Division of Pediatric General and Thoracic Surgery, UPMC Children’s Hospital of Pittsburgh, University of Pittsburgh Medical Center, Pittsburgh, PA, United States
| | - Matthew B. Rogers
- Department of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, United States
- Division of Pediatric General and Thoracic Surgery, UPMC Children’s Hospital of Pittsburgh, University of Pittsburgh Medical Center, Pittsburgh, PA, United States
| | - Michael J. Morowitz
- Department of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, United States
- Division of Pediatric General and Thoracic Surgery, UPMC Children’s Hospital of Pittsburgh, University of Pittsburgh Medical Center, Pittsburgh, PA, United States
| | - Jon D. Piganelli
- Department of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, United States
- Division of Pediatric General and Thoracic Surgery, UPMC Children’s Hospital of Pittsburgh, University of Pittsburgh Medical Center, Pittsburgh, PA, United States
| | - Qian Wang
- Department of Pathology, UPMC Children’s Hospital of Pittsburgh, University of Pittsburgh Medical Center, Pittsburgh, PA, United States
| | - Kevin P. Mollen
- Department of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, United States
- Division of Pediatric General and Thoracic Surgery, UPMC Children’s Hospital of Pittsburgh, University of Pittsburgh Medical Center, Pittsburgh, PA, United States
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Surdea-Blaga T, Ismaiel A, Jaaouani A, Leucuta DC, Elsayed A, Ismaiel M, Ben Ameur I, Al Srouji N, Popa SL, Grad S, Ensar D, Dumitrascu DL. Adiponectin Levels in Inflammatory Bowel Disease: A Systematic Review and Meta-Analysis. Dig Dis 2023; 41:860-871. [PMID: 37385235 DOI: 10.1159/000531614] [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: 01/23/2023] [Accepted: 06/12/2023] [Indexed: 07/01/2023]
Abstract
INTRODUCTION Adipose tissue plays an important role in the pathogenesis of inflammatory conditions. The role of adipokines in inflammatory bowel disease (IBD) has been evaluated in the current literature with conflicting results. The aim of this study was to evaluate adiponectin levels in IBD patients, including Crohn's disease (CD) and ulcerative colitis (UC), compared to controls, as well as further subgroup analyses. Hence, assessing the potential role of adiponectin as a surrogate marker. METHODS We performed a systematic electronic search on PubMed, Embase, Scopus, and Cochrane Library, including observational or interventional studies evaluating serum or plasma adiponectin levels in IBD patients in humans. The primary summary outcome was the mean difference (MD) in serum or plasma adiponectin levels between IBD patients versus controls. Subgroup analyses were conducted involving adiponectin levels in CD and UC compared to controls, as well as CD compared to UC. RESULTS A total of 20 studies were included in our qualitative synthesis and 14 studies in our quantitative synthesis, with a total population sample of 2,085 subjects. No significant MD in serum adiponectin levels was observed between IBD patients versus controls {-1.331 (95% confidence interval [CI]: -3.135-0.472)}, UC patients versus controls (-0.213 [95% CI: -1.898-1.472]), and CD patients versus controls (-0.851 [95% CI: -2.263-0.561]). Nevertheless, a significant MD was found between UC patients versus CD patients (0.859 [95% CI: 0.097-1.622]). CONCLUSIONS Serum adiponectin levels were not able to differentiate between IBD, UC, and CD patients compared to controls. However, significantly higher serum adiponectin levels were observed in UC compared to CD patients.
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Affiliation(s)
- Teodora Surdea-Blaga
- 2nd Department of Internal Medicine, "Iuliu Hatieganu" University of Medicine and Pharmacy, Cluj-Napoca, Romania
| | - Abdulrahman Ismaiel
- 2nd Department of Internal Medicine, "Iuliu Hatieganu" University of Medicine and Pharmacy, Cluj-Napoca, Romania
| | - Ayman Jaaouani
- Faculty of Medicine, "Iuliu Hatieganu" University of Medicine and Pharmacy, Cluj-Napoca, Romania
| | - Daniel-Corneliu Leucuta
- Department of Medical Informatics and Biostatistics, "Iuliu Hatieganu" University of Medicine and Pharmacy, Cluj-Napoca, Romania
| | - Abdalla Elsayed
- Department of Internal Medicine, County Emergency Hospital Ilfov, Bucharest, Romania
| | - Mohamed Ismaiel
- Department of General Surgery, Connolly Hospital Blanchardstown, Dublin, Ireland
| | - Inès Ben Ameur
- Faculty of Medicine, "Iuliu Hatieganu" University of Medicine and Pharmacy, Cluj-Napoca, Romania
| | - Nahlah Al Srouji
- 2nd Department of Internal Medicine, "Iuliu Hatieganu" University of Medicine and Pharmacy, Cluj-Napoca, Romania
| | - Stefan-Lucian Popa
- 2nd Department of Internal Medicine, "Iuliu Hatieganu" University of Medicine and Pharmacy, Cluj-Napoca, Romania
| | - Simona Grad
- 2nd Department of Internal Medicine, "Iuliu Hatieganu" University of Medicine and Pharmacy, Cluj-Napoca, Romania
| | - Dilara Ensar
- Department of Medicine, Tallaght University Hospital, Dublin, Ireland
| | - Dan L Dumitrascu
- 2nd Department of Internal Medicine, "Iuliu Hatieganu" University of Medicine and Pharmacy, Cluj-Napoca, Romania
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12
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Magalhaes D, Peyrin-Biroulet L, Estevinho MM, Danese S, Magro F. Pursuing neutrophils: systematic scoping review on blood-based biomarkers as predictors of treatment outcomes in inflammatory bowel disease. Therap Adv Gastroenterol 2023; 16:17562848231155987. [PMID: 36923488 PMCID: PMC10009059 DOI: 10.1177/17562848231155987] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/27/2022] [Accepted: 01/23/2023] [Indexed: 03/14/2023] Open
Abstract
Background Long-term management of inflammatory bowel diseases (IBD) is challenging and the identification of reliable predictors for treatment outcomes is an unmet need. Neutrophil-related biomarkers have been mainly studied in the feces, but blood analyses have inherent advantages. Objective To review the recent learnings on the ability of blood-based neutrophil-expressed biomarkers to predict treatment outcomes in IBD. Design Systematic scoping review. Data sources and methods We performed a literature search in Pubmed, EMBASE, SCOPUS, Web of Science, ScienceDirect, and Cochrane Central Register of Controlled Trials from inception until May 2022 according to Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines. All human studies associating blood-based neutrophil-related compounds with the prediction of disease progression, complication onset, or treatment outcomes were included. Results From 1032 retrieved entries, 34 studies were selected, 32 published in 2013 or later. In all, 17 biomarkers from granules, cytoplasm, plasmatic membrane, and plasma were explored. In total, 1850 Crohn's disease (CD) and 1122 ulcerative colitis non-duplicated patients were included. The most mentioned biomarkers were nCD64, serum calprotectin (SC), oncostatin M (OSM), neutrophil elastase-generated calprotectin fragment (CPa9-HNE), and triggering receptor expressed on myeloid cells 1 (TREM1). Six biomarkers showed promising results: OSM, SC, eNAMPT, nCD64, TREM1, and CPa9-HNE. Variable positive signals were found for human neutrophil peptide 1-3, LL-37, S100A12, and neutrophil gelatinase-associated lipocalin. No predictive ability was found for the remaining markers. Sharing a neutrophil compartment did not indicate similar behavior. Conclusion Advances in the last decade began to unveil the untapped potential of the readily accessible blood neutrophil-expressed biomarkers, especially nCD64, TREM1, and CPa9-HNE. Current evidence suggests that future research should focus on well-defined subpopulations instead of a one-size-fits-all biomarker. Registration https://osf.io/kes9a.
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Affiliation(s)
- Diogo Magalhaes
- Department of Biomedicine, Unit of Pharmacology and Therapeutics, Faculty of Medicine, University of Porto, Porto, Portugal
| | - Laurent Peyrin-Biroulet
- Department of Gastroenterology and Inserm NGERE U1256, University Hospital of Nancy, University of Lorraine, Vandoeuvre-lès-Nancy, France
| | - Maria Manuela Estevinho
- Department of Biomedicine, Unit of Pharmacology and Therapeutics, Faculty of Medicine, University of Porto, Porto, Portugal
- Department of Gastroenterology, Vila Nova de Gaia/Espinho Hospital Center, Vila Nova de Gaia, Portugal
| | - Silvio Danese
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy
- IBD center, Humanitas Research Hospital, IRCCS, Rozzano, Milan, Italy
| | - Fernando Magro
- Department of Biomedicine, Unit of Pharmacology and Therapeutics, Faculty of Medicine, University of Porto, Rua Dr. Plácido Costa, 3, Porto, 4200-450, Portugal
- Department of Gastroenterology, São João Hospital University Centre, Porto, Portugal
- Center for Health Technology and Services Research (CINTESIS), Porto, Portugal
- Unidade de Farmacologia Clínica, São João Hospital University Centre, Porto, Portugal
- Portuguese Inflammatory Bowel Disease group (GEDII)
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Gu P, Dube S, McGovern DPB. Medical and Surgical Implications of Mesenteric Adipose Tissue in Crohn's Disease: A Review of the Literature. Inflamm Bowel Dis 2023; 29:458-469. [PMID: 35731568 DOI: 10.1093/ibd/izac120] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/17/2022] [Indexed: 12/09/2022]
Abstract
Mesenteric adipose tissue (MAT) has gained substantial attention as an active player in Crohn's disease (CD), but its clinical significance is poorly understood and likely reflects, in part, difficulties assessing MAT noninvasively. Recent radiologic studies have identified candidate surrogate markers that may reflect inflammatory alterations of MAT in CD and have found that certain features including visceral adipose tissue may inform risk of complicated disease behavior, risk for surgery, and postoperative outcomes. Additionally, emerging surgical data have suggested MAT may even be a therapeutic target to mitigate postoperative recurrence of CD. However, the current studies have variable results, reduced sample sizes, and methodological limitations that preclude incorporating the radiologic and surgical findings into clinical practice. Nonetheless, the results are promising and potentially have important implications for the medical and surgical management of CD, which merits that additional studies are warranted. Thus, we have reviewed the available literature on the medical and surgical implications of MAT in CD to summarize our current understanding and identify gaps in knowledge to inform future investigations.
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Affiliation(s)
- Phillip Gu
- Karsh Division of Gastroenterology, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA
| | - Shishir Dube
- Karsh Division of Gastroenterology, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA
| | - Dermot P B McGovern
- Karsh Division of Gastroenterology, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA
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Colombo G, Caviglia GP, Ravera A, Tribocco E, Frara S, Rosso C, Travelli C, Genazzani AA, Ribaldone DG. NAMPT and NAPRT serum levels predict response to anti-TNF therapy in inflammatory bowel disease. Front Med (Lausanne) 2023; 10:1116862. [PMID: 36817780 PMCID: PMC9928959 DOI: 10.3389/fmed.2023.1116862] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2022] [Accepted: 01/17/2023] [Indexed: 02/04/2023] Open
Abstract
BACKGROUND Nicotinamide phosphoribosyltransferase (NAMPT) and nicotinic acid phosphoribosyl transferase (NAPRT) are key intracellular enzymes that participate in the biosynthesis on NAD but have also been shown to be released as proinflammatory cytokines. A number of reports have shown that circulating NAMPT is increased in serum of patients with inflammatory disorders, including inflammatory bowel diseases (IBD), while nothing is known regarding circulating NAPRT and the presence of both cytokines in IBD patient stools. In the present study, we evaluated eNAMPT and eNAPRT levels in a large cohort of IBD patients not on biological therapy and in a subset that then was prescribed biologics. METHODS We conducted a retro-perspective study on 180 patients, of which 111 underwent subsequent biological treatment (adalimumab, vedolizumab, and ustekinumab). We analyzed eNAMPT and eNAPRT concentrations in serum and faces of IBD patients, correlating them with response to biologics. RESULTS We now report that eNAMPT and eNAPRT are significantly increased in both serum and stools of IBD patients. NAMPT and NAPRT levels correlate with disease severity, with C reactive protein and with serum IL-6 levels. Importantly, levels of NAMPT in patients starting treatment with adalimumab correlate with response failure at three months: patients with levels above 4 ng/ml were significantly less likely to obtain benefit. Serum NAMPT as a biomarker of response yields a sensitivity of 91% and a specificity of 100%. CONCLUSION The present work strongly suggests that a prospective trial evaluating eNAMPT and eNAPRT levels in relation to response to biologicals in IBD should be initiated.
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Affiliation(s)
- Giorgia Colombo
- Department of Pharmaceutical Sciences, Università del Piemonte Orientale, Novara, Italy
| | - Gian Paolo Caviglia
- Division of Gastroenterology, Department of Medical Sciences, Università di Torino, Turin, Italy
| | - Alberto Ravera
- Division of Gastroenterology, Department of Medical Sciences, Università di Torino, Turin, Italy
| | - Elisa Tribocco
- Division of Gastroenterology, Department of Medical Sciences, Università di Torino, Turin, Italy
| | - Simone Frara
- Division of Gastroenterology, Department of Medical Sciences, Università di Torino, Turin, Italy
| | - Chiara Rosso
- Division of Gastroenterology, Department of Medical Sciences, Università di Torino, Turin, Italy
| | - Cristina Travelli
- Department of Drug Sciences, Università degli Studi di Pavia, Pavia, Italy
| | - Armando A. Genazzani
- Department of Pharmaceutical Sciences, Università del Piemonte Orientale, Novara, Italy
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15
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Roczniak W, Szymlak A, Mazur B, Chobot A, Stojewska M, Oświęcimska J. Nutritional Status and Selected Adipokines in Children with Irritable Bowel Syndrome. Nutrients 2022; 14:nu14245282. [PMID: 36558441 PMCID: PMC9782519 DOI: 10.3390/nu14245282] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2022] [Revised: 11/29/2022] [Accepted: 12/09/2022] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND The aim of this study was to assess the nutritional status and serum concentrations of adipokines in children with irritable bowel syndrome (IBS) and healthy controls. We also sought to evaluate their relation to metabolic parameters. METHODS We studied 33 IBS patients (11 girls, 22 boys) aged 5-17 years and 30 healthy age-matched controls (11 girls, 19 boys). The analysis included anthropometric measurements, body composition parameter measurements using bioimpedance, and biochemical tests and measurements of serum concentrations of leptin, adiponectin, chemerin, and omentin-1. RESULTS The results of the anthropometric measurements were comparable between the patients and the controls. The patients had higher triglycerides, HOMA-IRs, and chemerin concentrations than the healthy subjects. The HDL cholesterol and omentin-1 levels were lower than in the controls. Leptin and adiponectin did not differ significantly between the groups. An analysis of the receiver operator curves (ROCs) showed that serum concentrations of chemerin ≥ 232.8 ng/mL had 30% sensitivity and 87% specificity when they were used to differentiate between children with IBS and healthy subjects. In the case of serum omentin-1 concentrations ≤ 279.4 ng/mL, the sensitivity and specificity were 60% and 80%, respectively. CONCLUSIONS The nutritional status of children with IBS did not differ from that of the healthy controls. We found significant differences in serum chemerin and omentin-1 concentrations between IBS patients and healthy children. These adipokines could be used as IBS biomarkers as they demonstrate good specificity and moderate sensitivity. The serum concentrations of chemerin and omentin-1 in IBS patients were related to nutritional status and insulin resistance.
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Affiliation(s)
- Wojciech Roczniak
- Institute of Medicine, Jan Grodek State University in Sanok, ul. Mickiewicza 21, 38-500 Sanok, Poland
- Correspondence:
| | - Agnieszka Szymlak
- Department of General Paediatrics, University Hospital No 1 in Zabrze, Medical University of Silesia in Katowice, ul. 3 Maja 13-15, 41-800 Zabrze, Poland
| | - Bogdan Mazur
- Department of Microbiology and Immunology, Faculty of Medical Sciences in Zabrze, Medical University of Silesia in Katowice, ul. Jordana 19, 41-808 Zabrze, Poland
| | - Agata Chobot
- Department of Pediatrics, Institute of Medical Sciences, University of Opole, al. W.Witosa 26, 45-401 Opole, Poland
| | - Małgorzata Stojewska
- Department of Pediatrics, Faculty of Medical Sciences in Zabrze, Medical University of Silesia in Katowice, ul. 3-Maja 13-15, 41-800 Zabrze, Poland
| | - Joanna Oświęcimska
- Institute of Medicine, Jan Grodek State University in Sanok, ul. Mickiewicza 21, 38-500 Sanok, Poland
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Michalak A, Kasztelan-Szczerbińska B, Cichoż-Lach H. Impact of Obesity on the Course of Management of Inflammatory Bowel Disease-A Review. Nutrients 2022; 14:3983. [PMID: 36235636 PMCID: PMC9573343 DOI: 10.3390/nu14193983] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2022] [Revised: 09/16/2022] [Accepted: 09/19/2022] [Indexed: 11/16/2022] Open
Abstract
It is already well-known that visceral adipose tissue is inseparably related to the pathogenesis, activity, and general outcome of inflammatory bowel disease (IBD). We are getting closer and closer to the molecular background of this loop, finding certain relationships between activated mesenteric tissue and inflammation within the lumen of the gastrointestinal tract. Recently, relatively new data have been uncovered, indicating a direct impact of body fat on the pattern of pharmacological treatment in the course of IBD. On the other hand, ileal and colonic types of Crohn's disease and ulcerative colitis appear to be more diversified than it was thought in the past. However, the question arises whether at this stage we are able to translate this knowledge into the practical management of IBD patients or we are still exploring the scientific background of this pathology, having no specific tools to be used directly in patients. Our review explores IBD in the context of obesity and associated disorders, focusing on adipokines, creeping fat, and possible relationships between these disorders and the treatment of IBD patients.
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Affiliation(s)
| | | | - Halina Cichoż-Lach
- Department of Gastroenterology, Medical University of Lublin, Jaczewski St 8, 20-954 Lublin, Poland
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Lee YH, Kim H, Nam S, Chu JR, Kim JH, Lim JS, Kim SE, Sung MK. Protective Effects of High-Fat Diet against Murine Colitis in Association with Leptin Signaling and Gut Microbiome. Life (Basel) 2022; 12:life12070972. [PMID: 35888062 PMCID: PMC9323536 DOI: 10.3390/life12070972] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2022] [Revised: 06/19/2022] [Accepted: 06/24/2022] [Indexed: 04/26/2023] Open
Abstract
Inflammatory bowel disease (IBD) is characterized by chronic intestinal-tract inflammation with dysregulated immune responses, which are partly attributable to dysbiosis. Given that diet plays a critical role in IBD pathogenesis and progression, we elucidated the effects of a high-fat diet (HFD) feeding on IBD development in relation to immune dysfunction and the gut microbiota. Five-week-old male C57BL/6J mice were fed either a normal diet (ND) or HFD for 14 weeks. The animals were further divided into ND, ND+ dextran sulfate sodium (DSS), HFD, and HFD+DSS treatment groups. The HFD+DSS mice exhibited lower body weight loss, lower disease activity index, longer colon length, and increased tight-junction protein expression and goblet-cell proportions compared with the ND+DSS mice. The T helper (h)1 and Th17 cell populations and pro-inflammatory cytokines involved in colitis pathogenesis were significantly more reduced in the HFD+DSS mice than in the ND+DSS mice. The HFD+DSS mice showed significantly increased serum leptin concentrations, colonic leptin receptor expression, enhanced anti-apoptotic AKT expression, and reduced pro-apoptotic MAPK and Bax expression compared with the ND+DSS mice, suggesting the involvement of the leptin-mediated pathway in intestinal epithelial cell apoptosis. The alterations in the gut-microbiota composition in the HFD+DSS group were the opposite of those in the ND+DSS group and rather similar to those of the ND group, indicating that the protective effects of HFD feeding against DSS-induced colitis are associated with changes in gut-microbiota composition. Overall, HFD feeding ameliorates DSS-induced colitis and colonic mucosal damage by reinforcing colonic barrier function and regulating immune responses in association with changes in gut-microbiota composition.
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Affiliation(s)
- Yun-Ha Lee
- Department of Food and Nutrition, Sookmyung Women’s University, Yongsan-gu, Seoul 04310, Korea; (Y.-H.L.); (H.K.); (J.-R.C.)
| | - Hyeyoon Kim
- Department of Food and Nutrition, Sookmyung Women’s University, Yongsan-gu, Seoul 04310, Korea; (Y.-H.L.); (H.K.); (J.-R.C.)
| | - Sorim Nam
- Division of Biological Sciences and Cellular Heterogeneity Research Center, Sookmyung Women’s University, Yongsan-gu, Seoul 04310, Korea; (S.N.); (J.-S.L.)
| | - Jae-Ryang Chu
- Department of Food and Nutrition, Sookmyung Women’s University, Yongsan-gu, Seoul 04310, Korea; (Y.-H.L.); (H.K.); (J.-R.C.)
| | - Jung-Hwan Kim
- Department of Pharmacology, School of Medicine, Institute of Health Sciences, Gyeongsang National University, Jinju 52727, Korea;
| | - Jong-Seok Lim
- Division of Biological Sciences and Cellular Heterogeneity Research Center, Sookmyung Women’s University, Yongsan-gu, Seoul 04310, Korea; (S.N.); (J.-S.L.)
| | - Sung-Eun Kim
- Department of Food and Nutrition, Sookmyung Women’s University, Yongsan-gu, Seoul 04310, Korea; (Y.-H.L.); (H.K.); (J.-R.C.)
- Correspondence: (S.-E.K.); (M.-K.S.); Tel.: +82-2-2077-7722 (S.-E.K.); +82-2-710-9395 (M.-K.S.)
| | - Mi-Kyung Sung
- Department of Food and Nutrition, Sookmyung Women’s University, Yongsan-gu, Seoul 04310, Korea; (Y.-H.L.); (H.K.); (J.-R.C.)
- Correspondence: (S.-E.K.); (M.-K.S.); Tel.: +82-2-2077-7722 (S.-E.K.); +82-2-710-9395 (M.-K.S.)
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Karaskova E, Kubickova V, Velganova-Veghova M, Geryk M, Foltenova H, Karasek D. Circulating Levels of WISP-1 (Wnt1-Inducible Signaling Pathway Protein 1) and Other Selected Adipokines in Children With Inflammatory Bowel Disease. Physiol Res 2022; 71:275-284. [DOI: 10.33549/physiolres.934854] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
Abstract
Wnt1 inducible protein-1 signaling pathway (WISP-1) is a relatively new adipokine involved in many cellular processes, including epithelial mucosa healing. The aim of the study was to compare circulating levels of WISP-1 and other selected adipokines [adiponectin, resistin and retinol-binding protein 4 (RBP-4)] in children with inflammatory bowel disease (IBD) with healthy controls and to investigate possible differences between Crohn's disease patients. (CD) or ulcerative colitis (UC). The study was performed as a case-control study. In addition to adipokines, anthropometric, lipid parameters, markers of inflammation or disease activity were evaluated in all participants. Compared to healthy controls (n=20), significantly lower levels of adiponectin and higher levels of resistin and WISP-1 were found in patients with IBD (n=58). Elevation of WISP-1 was detected only in the CD group (n=31). There were no differences in RBP-4 levels between the groups. Adiponectin, WISP-1 and RBP-4 were independently associated with body mass index only, resistin levels were associated with C-reactive protein levels and leukocyte counts. Adverse adipokines production reflects presence of dysfunctional fat tissue in IBD patients. Higher levels of WISP-1 in CD compared to patients with UC may indicate a specific role for mesenteric adipose tissue in WISP-1 production.
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19
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Suau R, Pardina E, Domènech E, Lorén V, Manyé J. The Complex Relationship Between Microbiota, Immune Response and Creeping Fat in Crohn's Disease. J Crohns Colitis 2022; 16:472-489. [PMID: 34528668 DOI: 10.1093/ecco-jcc/jjab159] [Citation(s) in RCA: 31] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
In the last decade, there has been growing interest in the pathological involvement of hypertrophic mesenteric fat attached to the serosa of the inflamed intestinal segments involved in Crohn's disease [CD], known as creeping fat. In spite of its protective nature, creeping fat harbours an aberrant inflammatory activity which, in an already inflamed intestine, may explain why creeping fat is associated with a greater severity of CD. The transmural inflammation of CD facilitates the interaction of mesenteric fat with translocated intestinal microorganisms, contributing to activation of the immune response. This may be not the only way in which microorganisms alter the homeostasis of this fatty tissue: intestinal dysbiosis may also impair xenobiotic metabolism. All these CD-related alterations have a functional impact on nuclear receptors such as the farnesoid X receptor or the peroxisome proliferator-activated receptor γ, which are implicated in regulation of the immune response, adipogenesis and the maintenance of barrier function, as well as on creeping fat production of inflammatory-associated cells such as adipokines. The dysfunction of creeping fat worsens the inflammatory course of CD and may favour intestinal fibrosis and fistulizing complications. However, our current knowledge of the pathophysiology and pathogenic role of creeping fat is controversial and a better understanding might provide new therapeutic targets for CD. Here we aim to review and update the key cellular and molecular alterations involved in this inflammatory process that link the pathological components of CD with the development of creeping fat.
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Affiliation(s)
- Roger Suau
- IBD Research Group, 'Germans Trias i Pujol' Research Institute (IGTP), Badalona (Catalonia), Spain.,Centro de Investigación Biomédica en Red (CIBER), Madrid, Spain
| | - Eva Pardina
- Biochemistry and Molecular Biomedicine Department, University of Barcelona, Barcelona (Catalonia), Spain
| | - Eugeni Domènech
- IBD Research Group, 'Germans Trias i Pujol' Research Institute (IGTP), Badalona (Catalonia), Spain.,Centro de Investigación Biomédica en Red (CIBER), Madrid, Spain.,Gastroenterology Department, 'Germans Trias i Pujol' University Hospital, Badalona (Catalonia), Spain
| | - Violeta Lorén
- IBD Research Group, 'Germans Trias i Pujol' Research Institute (IGTP), Badalona (Catalonia), Spain.,Centro de Investigación Biomédica en Red (CIBER), Madrid, Spain
| | - Josep Manyé
- IBD Research Group, 'Germans Trias i Pujol' Research Institute (IGTP), Badalona (Catalonia), Spain.,Centro de Investigación Biomédica en Red (CIBER), Madrid, Spain
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20
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Weissman S, Patel K, Kolli S, Lipcsey M, Qureshi N, Elias S, Walfish A, Swaminath A, Feuerstein JD. Obesity in Inflammatory Bowel Disease Is Associated with Early Readmissions Characterised by an Increased Systems and Patient-level Burden. J Crohns Colitis 2021; 15:1807-1815. [PMID: 33999137 DOI: 10.1093/ecco-jcc/jjab088] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
BACKGROUND AND AIMS Rates of obesity are rising in patients with inflammatory bowel disease [IBD]. We conducted a US population-based study to determine the effects of obesity on outcomes in hospitalised patients with IBD. METHODS We searched the Nationwide Readmissions Database 2016-2017 to identify all adult patients hospitalised for IBD, using ICD-10 codes. We compared obese (body mass index [BMI] ≥ 30) vs non-obese [BMI < 30] patients with IBD to evaluate the independent effects of obesity on readmission, mortality, and other hospital outcomes. Multivariate regression and propensity matching were performed. RESULTS We identified 143 190 patients with IBD, of whom 9.1% were obese. Obesity was independently associated with higher all-cause readmission at 30 days {18% vs 13% (adjusted odds ratio [aOR] 1.16, p = 0.005)} and 90 days (29% vs 21% [aOR 1.27, p < 0.0001]), as compared with non-obese patients, with similar findings upon a propensity-matched sensitivity analysis. Obese and non-obese patients had similar risks of mortality on index admission [0.24% vs 0.31%, p = 0.18] and readmission [1.5% vs 1.8% p = 0.3]. Obese patients had longer [5.3 vs 4.9 days] and more expensive [USD12,195 vs USD11,154] hospitalisations on index admission. Obesity did not affect the risk of intestinal surgery or bowel obstruction. Compared with index admissions, readmissions were characterised by increased mortality [6-fold], health care use, and bowel obstruction [3-fold] [all p < 0.0001]. CONCLUSIONS Obesity in IBD appears to be associated with increased early readmission, characterised by a higher burden, despite the introduction of weight-based therapeutics. Prevention of obesity should be a focus in the treatment of IBD to decrease readmission and health care burden.
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Affiliation(s)
- Simcha Weissman
- Department of Medicine, Hackensack Meridian Health Palisades Medical Center, North Bergen, NJ, USA
| | - Kirtenkumar Patel
- Department of Medicine, North Shore University Hospital, Conway, SC, USA
| | - Sindhura Kolli
- Department of Medicine, NYU Grossman School of Medicine, New York, NY, USA
| | - Megan Lipcsey
- Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
| | - Nabeel Qureshi
- Department of Medicine, Hackensack Meridian Health Palisades Medical Center, North Bergen, NJ, USA
| | - Sameh Elias
- Department of Medicine, Hackensack Meridian Health Palisades Medical Center, North Bergen, NJ, USA
| | - Aaron Walfish
- Department of Gastroenterology and Hepatology, Icahn School of Medicine at Mount Sinai, Elmhurst Hospital Center, Elmhurst, NY, USA
| | - Arun Swaminath
- Division of Gastroenterology, Inflammatory Bowel Disease Program, Lenox Hill Hospital, New York, NY, USA
| | - Joseph D Feuerstein
- Division of Gastroenterology, Hepatology, and Nutrition, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
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21
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Serum Levels of Chemerin in Patients with Inflammatory Bowel Disease as an Indicator of Anti-TNF Treatment Efficacy. J Clin Med 2021; 10:jcm10194615. [PMID: 34640632 PMCID: PMC8509701 DOI: 10.3390/jcm10194615] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2021] [Revised: 10/03/2021] [Accepted: 10/05/2021] [Indexed: 12/20/2022] Open
Abstract
Chemerin belongs to the adipokines—proteins secreted by white adipose tissue. It plays an important role in angiogenesis and metabolism and its levels correlate with inflammation severity in many clinical states. Circulating chemerin levels in IBD are only rarely evaluated, with inconsistent results. The possible impact of anti-TNF therapy treatment in IBD on chemerin levels has not been addressed. The study aim was to evaluate the serum levels of chemerin in patients with inflammatory bowel disease (IBD), depending on disease severity as well as anti-TNF treatment. Serum chemerin was measured with ELISA in 77 patients with IBD as well as in 42 healthy controls (HCs). Twenty-six participants who underwent anti-TNF therapy were re-examined after 14 weeks. Overall, IBD patients had significantly higher serum chemerin levels than HCs. In patients with IBD exacerbation, chemerin levels were significantly higher compared to the remission group. Serum chemerin levels were significantly higher in UC patients compared to CD. Chemerin correlated with the severity of CD, but not with UC. Serum levels of chemerin decreased significantly after 14 weeks of anti-TNF treatment. Chemerin correlated with the clinical severity of IBD, and its levels decreased after anti-TNF treatment, which suggests its relationship with disease activity. It may be assumed that chemerin levels may possibly be useful for anti-TNF clinical course and treatment monitoring.
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22
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Hyun CK. Molecular and Pathophysiological Links between Metabolic Disorders and Inflammatory Bowel Diseases. Int J Mol Sci 2021; 22:ijms22179139. [PMID: 34502047 PMCID: PMC8430512 DOI: 10.3390/ijms22179139] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2021] [Revised: 08/21/2021] [Accepted: 08/22/2021] [Indexed: 02/07/2023] Open
Abstract
Despite considerable epidemiological evidence indicating comorbidity between metabolic disorders, such as obesity, type 2 diabetes, and non-alcoholic fatty liver disease, and inflammatory bowel diseases (IBD), such as Crohn’s disease and ulcerative colitis, as well as common pathophysiological features shared by these two categories of diseases, the relationship between their pathogenesis at molecular levels are not well described. Intestinal barrier dysfunction is a characteristic pathological feature of IBD, which also plays causal roles in the pathogenesis of chronic inflammatory metabolic disorders. Increased intestinal permeability is associated with a pro-inflammatory response of the intestinal immune system, possibly leading to the development of both diseases. In addition, dysregulated interactions between the gut microbiota and the host immunity have been found to contribute to immune-mediated disorders including the two diseases. In connection with disrupted gut microbial composition, alterations in gut microbiota-derived metabolites have also been shown to be closely related to the pathogeneses of both diseases. Focusing on these prominent pathophysiological features observed in both metabolic disorders and IBD, this review highlights and summarizes the molecular risk factors that may link between the pathogeneses of the two diseases, which is aimed at providing a comprehensive understanding of molecular mechanisms underlying their comorbidity.
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Affiliation(s)
- Chang-Kee Hyun
- School of Life Science, Handong Global University, Pohang 37554, Gyungbuk, Korea
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23
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Akazawa Y, Morisaki T, Fukuda H, Norimatsu K, Shiota J, Hashiguchi K, Tabuchi M, Kitayama M, Matsushima K, Yamaguchi N, Kondo H, Fujita F, Takeshita H, Nakao K, Takeshima F. Significance of serum palmitoleic acid levels in inflammatory bowel disease. Sci Rep 2021; 11:16260. [PMID: 34376800 PMCID: PMC8355139 DOI: 10.1038/s41598-021-95923-6] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2021] [Accepted: 06/28/2021] [Indexed: 01/22/2023] Open
Abstract
Inflammatory bowel diseases (IBDs), including ulcerative colitis (UC) and Crohn’s disease (CD), are chronic intestinal diseases of unknown etiology that present with variable disease extents and outcomes. The use of biomarkers for the diagnosis and management of IBDs is considered beneficial. Palmitoleic acid (PO) is an adipose tissue-derived mono-unsaturated free fatty acid that potentially serves as a lipokine in metabolic and inflammatory diseases. The aim of this study was to investigate the significance of PO levels in the serum of patients with UC and CD. The study included patients with UC (n = 22), patients with CD (n = 35), and controls (n = 22). The levels of serum PO were analyzed using gas chromatography. The association of serum PO levels with the clinical features and disease outcomes in IBD was examined. Serum PO levels were significantly higher in patients with CD than in controls, whereas no difference in these levels was observed between patients with UC and controls. Serum PO levels were significantly associated with the CD activity index. Additionally, high serum PO levels were associated with an increased risk of surgical intervention requirement during follow-up. In a pilot study with a few patients, high PO levels were observed in the mesenteric tissue in the active disease site of patients with CD (n = 7) compared with those with colon cancer (n = 6). Elevated serum PO levels might serve as a marker for local inflammation and prognosis in patients with CD.
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Affiliation(s)
- Yuko Akazawa
- Tissue and Histopathology Section, Atomic Bomb Disease Institute, Nagasaki University, Nagasaki, Japan.
| | | | | | - Kiyuu Norimatsu
- Department of Gastroenterology and Hepatology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
| | - Junya Shiota
- Department of Gastroenterology and Hepatology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
| | - Keiichi Hashiguchi
- Department of Gastroenterology and Hepatology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
| | - Maiko Tabuchi
- Department of Gastroenterology and Hepatology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
| | - Moto Kitayama
- Department of Gastroenterology and Hepatology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
| | - Kayoko Matsushima
- Department of Gastroenterology and Hepatology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
| | - Naoyuki Yamaguchi
- Department of Gastroenterology and Hepatology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
| | - Hisayoshi Kondo
- Biostatistics Section, Division of Scientific Data Registry, Atomic Bomb Disease Institute, Nagasaki University Graduate School of Medicine, Nagasaki, Japan
| | | | | | - Kazuhiko Nakao
- Department of Gastroenterology and Hepatology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
| | - Fuminao Takeshima
- Department of Gastroenterology and Hepatology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.,Nagasaki Goto Chuoh Hospital, Goto, Japan
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24
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Karaskova E, Velganova-Veghova M, Geryk M, Foltenova H, Kucerova V, Karasek D. Role of Adipose Tissue in Inflammatory Bowel Disease. Int J Mol Sci 2021; 22:4226. [PMID: 33921758 PMCID: PMC8073530 DOI: 10.3390/ijms22084226] [Citation(s) in RCA: 43] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2021] [Revised: 04/05/2021] [Accepted: 04/16/2021] [Indexed: 12/12/2022] Open
Abstract
Inflammatory bowel diseases (IBDs), chronic inflammatory disorders affecting the gastrointestinal tract, include Crohn's disease and ulcerative colitis. There are increasing clinical and experimental data showing that obesity, especially visceral adiposity, plays a substantial role in the pathogenesis of IBD. Obesity seems to be an important risk factor also for IBD disease severity and clinical outcomes. Visceral adipose tissue is an active multifunctional metabolic organ involved in lipid storage and immunological and endocrine activity. Bowel inflammation penetrates the surrounding adipose tissue along the mesentery. Mesenteric fat serves as a barrier to inflammation and controls immune responses to the translocation of gut bacteria. At the same time, mesenteric adipose tissue may be the principal source of cytokines and adipokines responsible for inflammatory processes associated with IBD. This review is particularly focusing on the potential role of adipokines in IBD pathogenesis and their possible use as promising therapeutic targets.
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Affiliation(s)
- Eva Karaskova
- Department of Pediatrics, Faculty of Medicine and Dentistry, Palacky University and University Hospital Olomouc, 77900 Olomouc, Czech Republic; (M.V.-V.); (M.G.); (H.F.)
| | - Maria Velganova-Veghova
- Department of Pediatrics, Faculty of Medicine and Dentistry, Palacky University and University Hospital Olomouc, 77900 Olomouc, Czech Republic; (M.V.-V.); (M.G.); (H.F.)
| | - Milos Geryk
- Department of Pediatrics, Faculty of Medicine and Dentistry, Palacky University and University Hospital Olomouc, 77900 Olomouc, Czech Republic; (M.V.-V.); (M.G.); (H.F.)
| | - Hana Foltenova
- Department of Pediatrics, Faculty of Medicine and Dentistry, Palacky University and University Hospital Olomouc, 77900 Olomouc, Czech Republic; (M.V.-V.); (M.G.); (H.F.)
| | - Veronika Kucerova
- Department of Clinical Biochemistry, University Hospital Olomouc, 77900 Olomouc, Czech Republic;
| | - David Karasek
- Third Department of Internal Medicine—Nephrology, Rheumatology and Endocrinology, Faculty of Medicine and Dentistry, Palacky University and University Hospital Olomouc, 77900 Olomouc, Czech Republic;
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25
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Visfatin Regulates Inflammatory Mediators in Mouse Intestinal Mucosa Through Toll-Like Receptors Signaling Under Lipopolysaccharide Stress. Arch Immunol Ther Exp (Warsz) 2021; 69:11. [PMID: 33856572 DOI: 10.1007/s00005-021-00611-y] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2020] [Accepted: 02/12/2021] [Indexed: 01/06/2023]
Abstract
Visfatin is a multifunctional protein involved in inflammatory immune stress. The aim of current study was to explore the role of visfatin in lipopolysaccharide (LPS)-induced intestinal mucosal inflammation and to confirm its cellular effect in inflammatory immune response through silencing of Toll-like receptors (TLRs). We divided Kunming mice into three groups: Saline group, LPS group, and LPS + visfatin group and performed hematoxylin and eosin staining, immunohistochemistry, quantitative polymerase chain reaction, Western blot, enzyme linked immunosorbent assay and RNA-seq analysis. Pretreatment of visfatin improves LPS-stimulated reduction of tight junction protein 1 (ZO-1) and secretory immunoglobulin A, inhibits overexpression of Claudin-1 and vascular endothelial growth factor, and reduces intestinal mucosal damage and inflammation. RNA-seq analysis of cellular transcriptomes indicated that visfatin is involved in down-regulation of mRNA level of TLR4 as well as attenuation of protein levels of TLR8 and nucleotide-binding oligomerization domain-containing protein 2, revealing that visfatin could reduce intestinal mucosal inflammation through TLR signaling pathway in mice ileum. In RAW264.7 cells, the genes silencing of Toll/IL-1R family, such as TLR4, TLR2, and IL-1R1, was accompanied by decreased expressions of inflammatory factors (TNF-α, IL-1β, IL-6 and MCP-1) along with lower cellular visfatin levels. Hence, visfatin maintains the intestinal mucosal barrier structure and attenuates the intestinal mucosal inflammation through the TLR signaling pathway. Likewise, the Toll/IL-1R family regulates the release of visfatin, which can participate in the inflammatory reaction through the regulation of inflammatory factors.
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26
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de Carvalho LGF, Lima WG, Coelho LGV, Cardoso VN, Fernandes SOA. Circulating Leptin Levels as a Potential Biomarker in Inflammatory Bowel Diseases: A Systematic Review and Meta-Analysis. Inflamm Bowel Dis 2021; 27:169-181. [PMID: 32095814 DOI: 10.1093/ibd/izaa037] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/23/2019] [Indexed: 12/20/2022]
Abstract
BACKGROUND The differential diagnosis of inflammatory bowel diseases (IBDs) between Crohn's disease (CD) and ulcerative colitis (UC) is important for designing an effective therapeutic regimen. However, without any adequate gold standard method for differential diagnosis currently, therapeutic design remains a major challenge in clinical practice. In this context, recent studies have showed that circulating leptin stands out as a potential biomarker for the categorization of IBDs. Thus, we aimed to summarize the current understanding of the prognostic and diagnostic value of serum leptin in patients with IBDs. METHODS A systematic search was performed in PubMed/MEDLINE, Scopus, Cochrane Library, and Web of Science databases. Articles that aimed to study the relationship between circulating levels of leptin and IBDs were included. Finally, the meta-analysis was performed with the mean serum leptin levels in patients with IBDs and healthy controls using RevMan 5.3 software, with I2 > 50% as a criterion for substantial heterogeneity. RESULTS Nineteen studies were included. Serum leptin levels among patients with IBDs and healthy controls did not show a significant difference (95% CI, -2.15 to 0.57; I2, 86%, P ≤ 0.00001). Similarly, there was no association of leptin levels with the activity of IBDs (95% CI, -0.24 to 0.06; I2, 50%; P = 0.13). However, serum leptin levels were significantly higher in patients with CD than those in patients with UC (95% CI, -2.09 to -0.37; I2, 7%; P ≤ 0.36). CONCLUSION This review suggested that serum leptin levels might be a promising biomarker to help in the differentiation between CD and UC.
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Affiliation(s)
- Larissa Gabriela Ferreira de Carvalho
- Laboratório de radioisótopos, Departamento de Análises Clínicas e Toxicológicas, Faculdade de Farmácia, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil
| | - William Gustavo Lima
- Laboratório de radioisótopos, Departamento de Análises Clínicas e Toxicológicas, Faculdade de Farmácia, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil
| | - Luiz Gonzaga Vaz Coelho
- Instituto ALFA de Gastrenterologia, Hospital das Clínicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil
| | - Valbert Nascimento Cardoso
- Laboratório de radioisótopos, Departamento de Análises Clínicas e Toxicológicas, Faculdade de Farmácia, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil
| | - Simone Odília Antunes Fernandes
- Laboratório de radioisótopos, Departamento de Análises Clínicas e Toxicológicas, Faculdade de Farmácia, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil
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27
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Bikbavova GR, Livzan MA, Shmurygina EA. Obesity and infl ammatory bowel disease: is there a link? EXPERIMENTAL AND CLINICAL GASTROENTEROLOGY 2020:133-141. [DOI: 10.31146/1682-8658-ecg-182-10-133-141] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 09/17/2024]
Affiliation(s)
- G. R. Bikbavova
- Federal state budgetary educational institution of higher education “Omsk State Medical University” of the Ministry of Healthcare of Russia
| | - M. A. Livzan
- Federal state budgetary educational institution of higher education “Omsk State Medical University” of the Ministry of Healthcare of Russia
| | - E. A. Shmurygina
- Federal state budgetary educational institution of higher education “Omsk State Medical University” of the Ministry of Healthcare of Russia
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28
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Tompa A, Åkesson K, Karlsson S, Faresjö M. Suppressed immune profile in children with combined type 1 diabetes and celiac disease. Clin Exp Immunol 2020; 201:244-257. [PMID: 32415995 PMCID: PMC7419926 DOI: 10.1111/cei.13454] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2020] [Revised: 05/06/2020] [Accepted: 05/06/2020] [Indexed: 12/22/2022] Open
Abstract
Children diagnosed with a combination of type 1 diabetes (T1D) and celiac disease (CD) show a dysregulated T helper type 1 (Th1)/Th17 response. Besides the cellular involvement, several soluble immune markers are involved in the autoimmune process of both T1D and CD. Only few studies have examined the peripheral pattern of different cytokines, chemokines and acute-phase proteins (APP) in children with combined T1D and CD. To our knowledge, no studies have evaluated the serum levels of adipocytokines and matrix metalloproteinases (MMPs) in this context. The purpose of the present study was to acquire more knowledge and to gain deeper understanding regarding the peripheral immunoregulatory milieu in children with both T1D and CD. The study included children diagnosed with both T1D and CD (n = 18), children with T1D (n = 27) or CD (n = 16) and reference children (n = 42). Sera were collected and analysis of 28 immune markers (cytokines, chemokines, APPs, adipocytokines and MMPs) was performed using the Luminex technique. The major findings showed that children with a double diagnosis had lower serum levels of interleukin (IL)-22, monocyte chemoattractant protein (MIP)-1α, monocyte chemoattractant protein (MCP)-1, procalcitonin, fibrinogen, visfatin and matrix metalloproteinase (MMP)-2. These results indicate a suppressed immune profile in children with combined T1D and CD, including Th17 cytokines, chemokines, APPs, adipocytokines and MMPs. We conclude that, besides cytokines and chemokines, other immune markers, e.g. APPs, adipocytokines and MMPs, are of importance for further investigations to elucidate the heterogeneous immune processes present in patients diagnosed with T1D in combination with CD.
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Affiliation(s)
- A. Tompa
- The Biomedical platformDepartment of Natural Science and BiomedicineSchool of Health and WelfareJönköping UniversityJönköpingSweden
- Division of DiagnosticsRegion Jönköping CountyJönköpingSweden
| | - K. Åkesson
- Department of PediatricsRyhov County HospitalJönköpingSweden
| | - S. Karlsson
- The Biomedical platformDepartment of Natural Science and BiomedicineSchool of Health and WelfareJönköping UniversityJönköpingSweden
| | - M. Faresjö
- The Biomedical platformDepartment of Natural Science and BiomedicineSchool of Health and WelfareJönköping UniversityJönköpingSweden
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29
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Tanrıverdi E, İliaz S, Cortuk M, Turan D, Chousein EGU, Gül Ş, Özgül MA, Çetinkaya E, Kirankaya A. Evaluation of Serum Biomarkers in Patients with Sarcoidosis: Can Visfatin Be a New Biomarker for Sarcoidosis? Turk Thorac J 2020; 21:145-149. [PMID: 32584229 DOI: 10.5152/turkthoracj.2019.180112] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2018] [Accepted: 05/03/2019] [Indexed: 11/22/2022]
Abstract
OBJECTIVES Sarcoidosis is a chronic systemic inflammatory disease that affects multiple organ systems. The role of biomarkers in the diagnosis and prognosis of sarcoidosis is increasing. Interest in the role of adipose tissue-mediated inflammation in the pathogenesis of inflammatory diseases has increased in recent years. Visfatin is a proinflammatory adipocytokine that has been studied for several inflammatory diseases such as diabetes mellitus, obesity, and metabolic syndrome. We aimed to assess serum visfatin levels in sarcoidosis and its relationship with other markers of inflammation such as C-reactive protein (CRP), angiotensin-converting enzyme (ACE) and erythrocyte sedimentation rate (ESR). MATERIALS AND METHODS We enrolled 59 patients with sarcoidosis and 21 healthy controls and measured plasma levels of visfatin, along with serum CRP, ESR, and ACE using ELISA (enzyme-linked immunosorbent assay) kits (Blue Gene Biotech, Shanghai, China). RESULTS Visfatin levels did not differ significantly between the patients and control subjects (29.9±15.8 ng/mL for patients and 23.93±16.73 ng/mL for controls, p=0.15), and there was no correlation between visfatin and serum CRP, ACE, or ESR in patients with sarcoidosis. CONCLUSION Visfatin is recently being discussed as a biomarker for inflammatory diseases in several studies, and results are controversial. In our study, no differences were found in the serum levels of visfatin between patients with sarcoidosis and the control group.
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Affiliation(s)
- Elif Tanrıverdi
- Department of Pulmonology, Yedikule Pulmonary Diseases and Thoracic Surgery Education and Research Hospital, İstanbul, Turkey
| | - Sinem İliaz
- Department of Pulmonology, Koç University School of Medicine, İstanbul, Turkey
| | - Mustafa Cortuk
- Department of Pulmonology, Karabük University School of Medicine, Karabük, Turkey
| | - Demet Turan
- Department of Pulmonology, Yedikule Pulmonary Diseases and Thoracic Surgery Education and Research Hospital, İstanbul, Turkey
| | - Efsun Gonca Uğur Chousein
- Department of Pulmonology, Yedikule Pulmonary Diseases and Thoracic Surgery Education and Research Hospital, İstanbul, Turkey
| | - Şule Gül
- Department of Pulmonology, Yedikule Pulmonary Diseases and Thoracic Surgery Education and Research Hospital, İstanbul, Turkey
| | - Mehmet Akif Özgül
- Department of Pulmonology, Yedikule Pulmonary Diseases and Thoracic Surgery Education and Research Hospital, İstanbul, Turkey
| | - Erdoğan Çetinkaya
- Department of Pulmonology, Yedikule Pulmonary Diseases and Thoracic Surgery Education and Research Hospital, İstanbul, Turkey
| | - Ayşegül Kirankaya
- Department of Biochemical, Bağcılar Education and Research Hospital, İstanbul, Turkey
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30
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Colombo G, Clemente N, Zito A, Bracci C, Colombo FS, Sangaletti S, Jachetti E, Ribaldone DG, Caviglia GP, Pastorelli L, De Andrea M, Naviglio S, Lucafò M, Stocco G, Grolla AA, Campolo M, Casili G, Cuzzocrea S, Esposito E, Malavasi F, Genazzani AA, Porta C, Travelli C. Neutralization of extracellular NAMPT (nicotinamide phosphoribosyltransferase) ameliorates experimental murine colitis. J Mol Med (Berl) 2020; 98:595-612. [PMID: 32338310 DOI: 10.1007/s00109-020-01892-0] [Citation(s) in RCA: 37] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2019] [Revised: 02/25/2020] [Accepted: 02/28/2020] [Indexed: 12/24/2022]
Abstract
Extracellular nicotinamide phosphoribosyltransferase (eNAMPT) is increased in inflammatory bowel disease (IBD) patients, and its serum levels correlate with a worse prognosis. In the present manuscript, we show that eNAMPT serum levels are increased in IBD patients that fail to respond to anti-TNFα therapy (infliximab or adalimumab) and that its levels drop in patients that are responsive to these therapies, with values comparable with healthy subjects. Furthermore, eNAMPT administration in dinitrobenzene sulfonic acid (DNBS)-treated mice exacerbates the symptoms of colitis, suggesting a causative role of this protein in IBD. To determine the druggability of this cytokine, we developed a novel monoclonal antibody (C269) that neutralizes in vitro the cytokine-like action of eNAMPT and that reduces its serum levels in rodents. Of note, this newly generated antibody is able to significantly reduce acute and chronic colitis in both DNBS- and dextran sulfate sodium (DSS)-induced colitis. Importantly, C269 ameliorates the symptoms by reducing pro-inflammatory cytokines. Specifically, in the lamina propria, a reduced number of inflammatory monocytes, neutrophils, Th1, and cytotoxic T lymphocytes are found upon C269 treatment. Our data demonstrate that eNAMPT participates in IBD and, more importantly, that eNAMPT-neutralizing antibodies are endowed with a therapeutic potential in IBD. KEY MESSAGES: What are the new findings? Higher serum eNAMPT levels in IBD patients might decrease response to anti-TNF therapy. The cytokine-like activity of eNAMPT may be neutralized with a monoclonal antibody. Neutralization of eNAMPT ameliorates acute and chronic experimental colitis. Neutralization of eNAMPT limits the expression of IBD inflammatory signature. Neutralization of eNAMPT impairs immune cell infiltration in lamina propria.
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Affiliation(s)
- Giorgia Colombo
- Department of Pharmaceutical Sciences, University of Eastern Piedmont, A. Avogadro, 28100, Novara, Italy
| | - Nausicaa Clemente
- Center for Translational Research on Autoimmune & Allergic Diseases (CAAD), Università del Piemonte Orientale, 28100, Novara, Italy
| | - Andrea Zito
- Lab of Immunogenetics, Department of Medical Sciences, University of Turin, 10100, Turin, Italy
| | - Cristiano Bracci
- Lab of Immunogenetics, Department of Medical Sciences, University of Turin, 10100, Turin, Italy
| | - Federico Simone Colombo
- Flow Cytometry and Cell Sorting Unit, Humanitas Clinical and Research Center - IRCCS, 20089, Rozzano, MI, Italy
| | - Sabina Sangaletti
- Molecular Immunology Unit, Department of Research, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milan, Italy
| | - Elena Jachetti
- Molecular Immunology Unit, Department of Research, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milan, Italy
| | | | - Gian Paolo Caviglia
- Division of Gastroenterology, Department of Medical Sciences, University of Turin, 10100, Turin, Italy
| | - Luca Pastorelli
- Department of Biomedical Sciences for Health, University of Milan, Milan, Italy
- Gastroenterology Unit, IRCCS Policlinico San Donato, San Donato Milanese, Italy
| | - Marco De Andrea
- Center for Translational Research on Autoimmune & Allergic Diseases (CAAD), Università del Piemonte Orientale, 28100, Novara, Italy
- Viral Pathogenesis Unit, Department of Public Health and Pediatric Sciences, Turin Medical School, 10126, Turin, Italy
| | - Samuele Naviglio
- Institute for Maternal and Child Health IRCCS Burlo Garofolo, 34137, Trieste, Italy
| | - Marianna Lucafò
- Department of Medicine, Surgery and Health Sciences, University of Trieste, 34137, Trieste, Italy
| | - Gabriele Stocco
- Department of Life Sciences, University of Trieste, 34137, Trieste, Italy
| | - Ambra A Grolla
- Department of Pharmaceutical Sciences, University of Eastern Piedmont, A. Avogadro, 28100, Novara, Italy
| | - Michela Campolo
- Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina (ME), Messina, ME, Italy
| | - Giovanna Casili
- Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina (ME), Messina, ME, Italy
| | - Salvatore Cuzzocrea
- Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina (ME), Messina, ME, Italy
| | - Emanuela Esposito
- Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina (ME), Messina, ME, Italy
| | - Fabio Malavasi
- Lab of Immunogenetics, Department of Medical Sciences, University of Turin, 10100, Turin, Italy
| | - Armando A Genazzani
- Department of Pharmaceutical Sciences, University of Eastern Piedmont, A. Avogadro, 28100, Novara, Italy
| | - Chiara Porta
- Department of Pharmaceutical Sciences, University of Eastern Piedmont, A. Avogadro, 28100, Novara, Italy.
- Center for Translational Research on Autoimmune & Allergic Diseases (CAAD), Università del Piemonte Orientale, 28100, Novara, Italy.
| | - Cristina Travelli
- Department of Pharmaceutical Sciences, Università degli Studi di Pavia, 27100, Pavia, Italy.
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Clinical assessment of risk factors for infection in inflammatory bowel disease patients. Int J Colorectal Dis 2020; 35:491-500. [PMID: 31915983 DOI: 10.1007/s00384-019-03501-0] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 12/26/2019] [Indexed: 02/04/2023]
Abstract
PURPOSE Recognizing patients with inflammatory bowel disease who are prone to infection would enable the adjustment of the type and intensity of immunosuppressive treatment. The aim of this study was to identify a clinical profile of risk for infections in IBD patients, based on the interaction of immunosuppressive treatment with factors inherent to the patient. METHODS A case-control study was performed among patients older than 18 years. Patients with any significant infection (any kind of severe or recurrent infection according to standard clinical criteria or a critical enough infection according to the patient) were defined as cases. Both cases and controls were randomly selected in a 1:3 ratio. All the period from diagnosis to the end of recruitment (June 2016) was analyzed. Risk factors for infection were identified by logistic regression analysis; the strength of association was reported by odds ratio (OR) with 95% confidence interval (95%CI). RESULTS A total of 112 cases and 270 controls were included. The independent risk factors for significant infection are the number of immunosuppressants (one drug: OR 1.28, 95% CI 0.53-3.11, two drugs: OR 2.37, 95% CI 1.01-5,56, and three drugs: OR 5.84, 95% CI 1.57-21.72), body mass index (OR 1.08; 95 %CI 1,01-1,16), the degree of comorbidity (OR 1.52; 95% CI 1.04-2.21), and the intensity of inflammatory activity (OR 1.43; 95% CI 1.19-1.71). CONCLUSIONS Regardless of immunosuppression, several patient factors such as comorbidity, body mass index, or the inflammatory activity of the disease determine the individual risk of infectious complications and should be considered for an adequate risk assessment.
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Jacenik D, Fichna J. Chemerin in immune response and gastrointestinal pathophysiology. Clin Chim Acta 2020; 504:146-153. [PMID: 32070869 DOI: 10.1016/j.cca.2020.02.008] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2019] [Revised: 02/09/2020] [Accepted: 02/10/2020] [Indexed: 02/07/2023]
Abstract
Chemerin is a multifunctional protein involved among others in adipogenesis, angiogenesis and lipid as well as glucose metabolism. Chemerin is an essential factor in promotion of chemotaxis of numerous immune cell types and plays an important role in several pathophysiologic conditions. Chemerin receptors are present on monocytes/macrophages, T cells, natural killer and dendritic cells as well as neutrophils. However, the role of chemerin and chemerin receptors in immune response and gastrointestinal diseases is still poorly understood. Accumulating, clinical and experimental studies observed disturbation of chemerin and chemerin receptors in a number of disorders including Barrett's esophagus, esophageal cancer, gastric cancer, hepatic dysfunction, irritable bowel syndrome, inflammatory bowel disease and colorectal cancer. Moreover, chemerin and chemerin receptors have been shown to regulate proliferation, migration and invasion of gastrointestinal and immune cells as well as cancer-associated fibroblasts. In this review we present the current state of knowledge about the contribution of chemerin to immune response and gastrointestinal disorders.
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Affiliation(s)
- Damian Jacenik
- University of Lodz, Faculty of Biology and Environmental Protection, Department of Cytobiochemistry, Pomorska St. 141/143, Lodz 90-236, Poland
| | - Jakub Fichna
- Medical University of Lodz, Faculty of Medicine, Department of Biochemistry, Mazowiecka St. 6/8, 92-215 Lodz, Poland.
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Role of Obesity, Mesenteric Adipose Tissue, and Adipokines in Inflammatory Bowel Diseases. Biomolecules 2019; 9:biom9120780. [PMID: 31779136 PMCID: PMC6995528 DOI: 10.3390/biom9120780] [Citation(s) in RCA: 83] [Impact Index Per Article: 13.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2019] [Revised: 11/14/2019] [Accepted: 11/15/2019] [Indexed: 12/11/2022] Open
Abstract
Inflammatory bowel diseases (IBDs) are a group of disorders which include ulcerative colitis and Crohn's disease. Obesity is becoming increasingly more common among patients with inflammatory bowel disease and plays a role in the development and course of the disease. This is especially true in the case of Crohn's disease. The recent results indicate a special role of visceral adipose tissue and particularly mesenteric adipose tissue, also known as "creeping fat", in pathomechanism, leading to intestinal inflammation. The involvement of altered adipocyte function and the deregulated production of adipokines, such as leptin and adiponectin, has been suggested in pathogenesis of IBD. In this review, we discuss the epidemiology and pathophysiology of obesity in IBD, the influence of a Western diet on the course of Crohn's disease and colitis in IBD patients and animal's models, and the potential role of adipokines in these disorders. Since altered body composition, decrease of skeletal muscle mass, and development of pathologically changed mesenteric white adipose tissue are well-known features of IBD and especially of Crohn's disease, we discuss the possible crosstalk between adipokines and myokines released from skeletal muscle during exercise with moderate or forced intensity. The emerging role of microbiota and the antioxidative and anti-inflammatory enzymes such as intestinal alkaline phosphatase is also discussed, in order to open new avenues for the therapy against intestinal perturbations associated with IBD.
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Kong Y, Zhang S, Wu R, Su X, Peng D, Zhao M, Su Y. New insights into different adipokines in linking the pathophysiology of obesity and psoriasis. Lipids Health Dis 2019; 18:171. [PMID: 31521168 PMCID: PMC6745073 DOI: 10.1186/s12944-019-1115-3] [Citation(s) in RCA: 48] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2019] [Accepted: 09/02/2019] [Indexed: 12/13/2022] Open
Abstract
Psoriasis is a chronic, systemic, hyper-proliferative immune-mediated inflammatory skin disease. The results of epidemiological investigations have shown that psoriasis affects around 2% of the general population worldwide, and the total number of psoriasis patients is more than 6 million in China. Apart from the skin manifestations, psoriasis has been verified to associate with several metabolic comorbidities, such as insulin resistance, diabetes and obesity. However, the underlying mechanism is still not elucidated. Adipocytes, considered as the active endocrine cells, are dysfunctional in obesity which displays increased synthesis and secretion of adipokines with other modified metabolic properties. Currently, growing evidence has pointed to the central role of adipokines in adipose tissue and the immune system, providing new insights into the effect of adipokines in linking the pathophysiology of obesity and psoriasis. In this review, we summarize the current understanding of the pathological role of adipokines and the potential mechanisms whereby different adipokines link obesity and psoriasis. Furthermore, we also provide evidence which identifies a potential therapeutic target aiming at adipokines for the management of these two diseases.
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Affiliation(s)
- Yi Kong
- Department of Dermatology, Hunan Key Laboratory of Medical Epigenomics, the Second Xiangya Hospital of Central South University, 139 Renmin Middle Road, Changsha, 410011, Hunan, China
| | - Suhan Zhang
- Department of Dermatology, Hunan Key Laboratory of Medical Epigenomics, the Second Xiangya Hospital of Central South University, 139 Renmin Middle Road, Changsha, 410011, Hunan, China
| | - Ruifang Wu
- Department of Dermatology, Hunan Key Laboratory of Medical Epigenomics, the Second Xiangya Hospital of Central South University, 139 Renmin Middle Road, Changsha, 410011, Hunan, China
| | - Xin Su
- Department of Cardiovascular Medicine, the Second Xiangya Hospital of Central South University, Changsha, Hunan, China
| | - Daoquan Peng
- Department of Cardiovascular Medicine, the Second Xiangya Hospital of Central South University, Changsha, Hunan, China
| | - Ming Zhao
- Department of Dermatology, Hunan Key Laboratory of Medical Epigenomics, the Second Xiangya Hospital of Central South University, 139 Renmin Middle Road, Changsha, 410011, Hunan, China.
| | - Yuwen Su
- Department of Dermatology, Hunan Key Laboratory of Medical Epigenomics, the Second Xiangya Hospital of Central South University, 139 Renmin Middle Road, Changsha, 410011, Hunan, China.
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35
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Exogenous leptin reinforces intestinal barrier function and protects from colitis. Pharmacol Res 2019; 147:104356. [DOI: 10.1016/j.phrs.2019.104356] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/26/2019] [Revised: 06/19/2019] [Accepted: 07/15/2019] [Indexed: 02/07/2023]
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Luo J, Li HP, Xu F, Wu BQ, Lin HC. Early diagnosis of necrotizing enterocolitis by plasma RELMβ and thrombocytopenia in preterm infants: A pilot study. Pediatr Neonatol 2019; 60:447-452. [PMID: 30799148 DOI: 10.1016/j.pedneo.2019.01.006] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/30/2018] [Revised: 11/20/2018] [Accepted: 01/15/2019] [Indexed: 11/16/2022] Open
Abstract
BACKGROUND As the inflammatory regulators, Resistin-like molecule β (RELMβ) and Resistin might be potential biomarkers of necrotizing enterocolitis (NEC), while thrombocytopenia is often related to the severity of NEC, clinical observation suggests that thrombocytopenia might be an early biomarker of NEC. The aim of this study was to evaluate whether RELMβ, Resistin and thrombocytopenia could be biomarkers for early diagnosis of NEC in preterm infants. METHODS From January 2016 to March 2018, twenty-nine NEC preterm infants who were diagnosed with NEC (Bell's stage ≥Ⅱ) by two independent neonatologists and twenty-nine non NEC preterm infants at neonatal intensive care unit in our hospital were enrolled in this case-control study. Preterm infants with a history of serious infections (sepsis, pneumonia), asphyxia, and congenital malformations were excluded from the study. The plasma RELMβ and Resistin were evaluated by enzyme linked immunosorbent assay (ELISA) and serum platelet levels were measured directly by ordinary light microscope at the diagnosis of NEC (Bell's stage ≥Ⅱ). RESULTS Plasma RELMβ levels in NEC group were significantly higher than control group (P < 0.05). The optimal cut-off value of RELMβ determined by receiver operating characteristic curve (ROC) was 378.3 ng/L. The overall estimates for sensitivity and specificity of high RELMβ concentrations in the detection of neonatal NEC were 71.4% and 91.7%, respectively. No significant difference was found in plasma Resistin levels between two groups (P > 0.05). If platelet level was less than 157 × 109/L, the sensitivity and specificity were 69.34% and 82.87%, respectively. Interestingly, the combination of RELMβ and thrombocytopenia increased sensitivity and specificity to 82.89% and 93.21%, respectively. CONCLUSION The combination of RELMβ and thrombocytopenia was a reliable biomarker for the early diagnosis of NEC in this study with 82.89% sensitivity and 93.21% specificity, respectively.
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Affiliation(s)
- Jun Luo
- Department of Neonatology, Bao'an Maternal and Child Health Hospital of Shenzhen, Jinan University, Guangdong, China
| | - Hong Ping Li
- Department of Neonatology, Shenzhen Children's Hospital, Shenzhen, China
| | - Fen Xu
- Department of Neonatology, Bao'an Maternal and Child Health Hospital of Shenzhen, Jinan University, Guangdong, China
| | - Ben Qing Wu
- Department of Neonatology, Guangming People's Hospital of Shenzhen, China
| | - Hung Chih Lin
- Department of Neonatology, China Medical University Children's Hospital, Taichung, Taiwan; School of Chinese Medicine, China Medical University, Taichung, Taiwan; Asia University Hospital, Asia University, Taichung, Taiwan.
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The Role of Adipose Tissue in the Pathogenesis and Therapeutic Outcomes of Inflammatory Bowel Disease. Cells 2019; 8:cells8060628. [PMID: 31234447 PMCID: PMC6627060 DOI: 10.3390/cells8060628] [Citation(s) in RCA: 53] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2019] [Revised: 06/16/2019] [Accepted: 06/18/2019] [Indexed: 02/06/2023] Open
Abstract
Though historically regarded as an inert energy store, adipose tissue is a complex endocrine organ, which is increasingly implicated in the pathogenesis of inflammatory bowel disease (IBD). Accumulating evidence points to visceral adipose tissue and specifically to its mesenteric component, or “creeping fat” as impacting on the disease course through its immunomodulatory properties. On the one hand, mesenteric fat acts as a physical barrier to inflammation and is involved in controlling host immune response to translocation of gut bacteria. On the other hand, however, there exists a strong link between visceral fat and complicated course of the disease with unfavorable therapeutic outcomes. Furthermore, “creeping fat” appears to play different roles in different IBD phenotypes, with the greatest pathogenetic contribution probably to an ileal form of Crohn’s disease. In this review, we summarize and discuss the existing literature on the subject and identify high-priority areas for future research. It may be that a better understanding of the role of mesenteric fat in IBD will determine new therapeutic targets and translate into improved clinical outcomes.
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38
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Neumann E, Lepper N, Vasile M, Riccieri V, Peters M, Meier F, Hülser ML, Distler O, Gay S, Mahavadi P, Günther A, Roeb E, Frommer KW, Diller M, Müller-Ladner U. Adipokine expression in systemic sclerosis lung and gastrointestinal organ involvement. Cytokine 2019; 117:41-49. [PMID: 30784899 DOI: 10.1016/j.cyto.2018.11.013] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2018] [Revised: 10/12/2018] [Accepted: 11/12/2018] [Indexed: 12/12/2022]
Abstract
OBJECTIVES The immunomodulatory properties of adipokines have previously been reported in autoimmune disorders. Less is known about the role of adipokines in systemic sclerosis (SSc). Lung and gastrointestinal tract are frequently involved in SSc; therefore, these organs were analyzed for adipokine expression as well as pulmonary samples of patients suffering from idiopathic pulmonary fibrosis (IPF) as comparison. METHODS Gastric samples (antrum, corpus) of SSc were analyzed immunohistochemically for adiponectin, resistin and visfatin compared with non-SSc related gastritis. Inflammatory cells were quantified in gastric samples and correlated with adipokine expression. Lung samples of SSc, IPF and healthy controls were also analyzed. Protein levels of lung tissue lysates and bronchoalveolar lavages (BAL) in minor fibrotic stages were measured by ELISA. RESULTS Lung sections of donor parenchyma showed significantly stronger adiponectin signals as IPF and SSc (donor vs. IPF: p < 0.0001). In SSc and IPF, resistin and visfatin were increased within immune cell infiltrates, but overall no difference in expression for resistin or visfatin compared to controls was observed. In BAL and lung protein lysates of early stages of fibrosis, adiponectin and visfatin were not reduced in IPF and SSc compared to controls. In gastric samples collected by standard endoscopic gastric biopsy, adiponectin was also significantly reduced in SSc- compared to non-SSc gastritis (p = 0.049) while resistin and visfatin were comparable although deeper fibrotic layers were not included in the respective samples. Adiponectin-positive tissues showed higher amounts of CD4+ but not CD8+ T cells. Controls showed no correlation between CD4+ T cells and resistin, whereas SSc showed significantly more CD4+ T cells in resistin-negative tissues. CONCLUSION Adipokines are expressed in gastric and lung samples of patients with SSc and in lung samples affected by IPF. Prominently, adiponectin levels were reduced in fibrotic SSc gastritic tissue as well as in IPF and SSc lung tissue. Consequently, adiponectin expression seems to be associated with fibrotic progression in the context of SSc and IPF.
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Affiliation(s)
- Elena Neumann
- Dept of Rheumatology and Clinical Immunology, Campus Kerckhoff, Justus-Liebig-University, Giessen, Germany.
| | - Nina Lepper
- Dept of Rheumatology and Clinical Immunology, Campus Kerckhoff, Justus-Liebig-University, Giessen, Germany
| | - Massimiliano Vasile
- Dept of Rheumatology and Clinical Immunology, Campus Kerckhoff, Justus-Liebig-University, Giessen, Germany; Dept Internal Medicine and Medical Specialties, Sapienza University Rome, Rome, Italy
| | - Valeria Riccieri
- Dept Internal Medicine and Medical Specialties, Sapienza University Rome, Rome, Italy
| | - Marvin Peters
- Dept of Rheumatology and Clinical Immunology, Campus Kerckhoff, Justus-Liebig-University, Giessen, Germany
| | - Florian Meier
- Dept of Rheumatology and Clinical Immunology, Campus Kerckhoff, Justus-Liebig-University, Giessen, Germany
| | - Marie-Lisa Hülser
- Dept of Rheumatology and Clinical Immunology, Campus Kerckhoff, Justus-Liebig-University, Giessen, Germany
| | - Oliver Distler
- Div Rheumatology, University Hospital Zurich, Zurich, Switzerland
| | - Steffen Gay
- Div Rheumatology, University Hospital Zurich, Zurich, Switzerland
| | - Poornima Mahavadi
- Med Clinic II, Pneumology, Justus-Liebig-University Giessen, Germany
| | - Andreas Günther
- Med Clinic II, Pneumology, Justus-Liebig-University Giessen, Germany
| | - Elke Roeb
- Med Clinic II, Gastroenterology, Justus-Liebig-University Giessen, Germany
| | - Klaus W Frommer
- Dept of Rheumatology and Clinical Immunology, Campus Kerckhoff, Justus-Liebig-University, Giessen, Germany
| | - Magnus Diller
- Dept of Rheumatology and Clinical Immunology, Campus Kerckhoff, Justus-Liebig-University, Giessen, Germany
| | - Ulf Müller-Ladner
- Dept of Rheumatology and Clinical Immunology, Campus Kerckhoff, Justus-Liebig-University, Giessen, Germany
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Neubauer K, Bednarz-Misa I, Walecka-Zacharska E, Wierzbicki J, Agrawal A, Gamian A, Krzystek-Korpacka M. Oversecretion and Overexpression of Nicotinamide Phosphoribosyltransferase/Pre-B Colony-Enhancing Factor/Visfatin in Inflammatory Bowel Disease Reflects the Disease Activity, Severity of Inflammatory Response and Hypoxia. Int J Mol Sci 2019; 20:E166. [PMID: 30621173 PMCID: PMC6337260 DOI: 10.3390/ijms20010166] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2018] [Revised: 12/23/2018] [Accepted: 12/28/2018] [Indexed: 02/07/2023] Open
Abstract
Nicotinamide phosphoribosyltransferase's (Nampt) association with inflammatory bowel disease (IBD) is unclear. The study was aimed at unraveling Nampt's clinical and diagnostic relevance. The serum concentration (Luminex-xMAP® technology) was measured in 113 patients with Crohn's disease (CD), 127 with ulcerative colitis (UC) and 60 non-IBD controls: 40 healthy individuals and 20 with irritable bowel syndrome (IBS). The leukocyte (44 CD/37 UC/19 IBS) and bowel expression (186 samples) was also evaluated (RT-qPCR). All were referred to IBD phenotype, activity, treatment, and inflammatory/nutritional/angiogenic/hypoxia indices. Serum-Nampt and leukocyte-Nampt were positively correlated and were more elevated in active-IBD than in IBS, with leukocyte-Nampt being a fair differential marker. Serum-Nampt in UC positively correlated with its clinical and endoscopic activity as well as with pro-inflammatory cytokines. Serum-Nampt ≤1.54 ng/mL was a good indicator of mucosal healing. The expression of Nampt was up-regulated both in inflamed and quiescent colon and reflected, similarly to leukocyte-Nampt, the clinical activity of IBD. Bowel-Nampt was independently associated with IL1B and hypoxia-inducible factor 1α (HIF1A) expression in inflamed bowel but with FGF2 expression in quiescent bowel. In summary, Nampt's elevation in IBD at local and systemic levels, and protein and mRNA levels, reflects IBD activity and is associated with inflammation, hypoxia (active) and tissue repair (inactive disease).
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Affiliation(s)
- Katarzyna Neubauer
- Department of Gastroenterology and Hepatology, Wroclaw Medical University, 50-556 Wroclaw, Poland.
| | - Iwona Bednarz-Misa
- Department of Medical Biochemistry, Wroclaw Medical University, 50-368 Wroclaw, Poland.
| | - Ewa Walecka-Zacharska
- Department of Food Hygiene and Consumer Health, Wroclaw University of Environmental and Life Sciences, 50-375 Wroclaw, Poland.
| | - Jaroslaw Wierzbicki
- Department of Minimally Invasive Surgery and Proctology, Wroclaw Medical University, 50-556 Wroclaw, Poland.
| | - Anil Agrawal
- The 2nd Department of General and Oncological Surgery, Wroclaw Medical University, 50-556 Wroclaw, Poland.
| | - Andrzej Gamian
- Department of Medical Biochemistry, Wroclaw Medical University, 50-368 Wroclaw, Poland.
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Kreuter R, Wankell M, Ahlenstiel G, Hebbard L. The role of obesity in inflammatory bowel disease. Biochim Biophys Acta Mol Basis Dis 2018; 1865:63-72. [PMID: 30352258 DOI: 10.1016/j.bbadis.2018.10.020] [Citation(s) in RCA: 34] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2018] [Revised: 09/27/2018] [Accepted: 10/16/2018] [Indexed: 02/06/2023]
Abstract
In just over a generation overweight and obesity has become a worldwide health concern. The ramifications for this on future health care costs and longevity are consequent, whilst increased adiposity is a harbinger for diabetes, kidney and bone failure, and cancer. An area of intense interest where the role of adiposity is avidly discussed is in inflammatory bowel disease (IBD), which presents mainly as Crohn's disease (CD) and ulcerative colitis (UC). Studies in patients associating IBD with a western diet are divergent. Nevertheless, elegant studies have found gene polymorphisms in humans that in murine models parallel the inflammatory and gut microbiome changes seen in IBD patients. However, an area not to be ignored are the alterations in adipocyte function with ensuing adiposity, in particular and a focus of this review, the dysregulation of the levels of adipocytokines such as leptin and adiponectin. Herein, we present and discuss the known influences of a western diet on IBD in patients and rodent models and how adipocytokines could influence the IBD disease process.
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Affiliation(s)
- Roxane Kreuter
- Department of Molecular and Cell Biology, The Centre for Molecular Therapeutics, James Cook University, Australian Institute of Tropical Health and Medicine, Townsville, QLD 4811, Australia
| | - Miriam Wankell
- Department of Molecular and Cell Biology, The Centre for Molecular Therapeutics, James Cook University, Australian Institute of Tropical Health and Medicine, Townsville, QLD 4811, Australia
| | - Golo Ahlenstiel
- Storr Liver Centre, Westmead Institute for Medical Research, Westmead Hospital and University of Sydney, Sydney, NSW 2145, Australia; Blacktown Clinical School, Western Sydney University, Blacktown Hospital, PO Box 792, Seven Hills, NSW 2147, Australia
| | - Lionel Hebbard
- Department of Molecular and Cell Biology, The Centre for Molecular Therapeutics, James Cook University, Australian Institute of Tropical Health and Medicine, Townsville, QLD 4811, Australia; Storr Liver Centre, Westmead Institute for Medical Research, Westmead Hospital and University of Sydney, Sydney, NSW 2145, Australia.
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41
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Sochal M, Mosińska P, Fichna J. Diagnostic value of chemerin in lower gastrointestinal diseases-a review. Peptides 2018; 108:19-24. [PMID: 30165089 DOI: 10.1016/j.peptides.2018.08.012] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/13/2018] [Revised: 08/21/2018] [Accepted: 08/26/2018] [Indexed: 12/14/2022]
Abstract
Chemerin is a protein secreted among others by adipose tissue and liver, with a dual pro- and anti-inflammatory role in the body. These molecules exert systemic effects by modulating tissue-specific immune response and metabolism. Chemerin isoforms correlate with the turnover of fatty acids and lipoproteins that could affect intestinal inflammation. Although chemerin may interact with three types of receptors, CMKLR1 is the best studied. In this paper we reviewed current knowledge about the relationship between chemerin and lower gastrointestinal (GI) diseases, such as irritable bowel syndrome (IBS), inflammatory bowel disease (IBD) and colorectal cancer (CRC). A more detailed understanding of the role of the adipose tissue in the GI tract will not only unravel the pathophysiology of chronic intestinal diseases, but may also indicate a new therapeutic tool for their management.
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Affiliation(s)
- Marcin Sochal
- Department of Biochemistry, Faculty of Medicine, Medical University of Lodz, Mazowiecka 6/8, 92-215 Lodz, Poland
| | - Paula Mosińska
- Department of Biochemistry, Faculty of Medicine, Medical University of Lodz, Mazowiecka 6/8, 92-215 Lodz, Poland
| | - Jakub Fichna
- Department of Biochemistry, Faculty of Medicine, Medical University of Lodz, Mazowiecka 6/8, 92-215 Lodz, Poland.
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42
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Zielińska A, Siwiński P, Sobolewska-Włodarczyk A, Wiśniewska-Jarosińska M, Fichna J, Włodarczyk M. The role of adipose tissue in the pathogenesis of Crohn's disease. Pharmacol Rep 2018; 71:105-111. [PMID: 30513401 DOI: 10.1016/j.pharep.2018.09.011] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2018] [Revised: 08/10/2018] [Accepted: 09/27/2018] [Indexed: 02/07/2023]
Abstract
Crohn's disease (CD) is a chronic, immune system-mediated inflammatory disease affecting gastrointestinal (GI) tract. The pathogenesis of the intestinal lesions is not entirely explained and understood: excessive activation of the immune system may come as a result of the interaction of environmental, genetic and infectious factors and the mediation of abnormal intestinal flora. The main objective of the current study is to further identify the role of adipose tissue in the pathogenesis of CD. Alterations in body fat distribution, accumulation of intra-abdominal white adipose tissue (WAT) and mesenteric obesity are well-known features of CD. Up to date, data concerning the role of WAT in the pathogenesis of CD is limited with only a few studies on the relationship between WAT and the course of the disease, as well as pro- and anti-inflammatory cytokine profile and general immune system functioning. In this review, we focus on the importance of physiological and pathophysiological WAT functions and secreted adipokines, which seem to have a vital role in the inflammatory and fibrotic processes in CD sufferers.
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Affiliation(s)
- Anna Zielińska
- Department of Biochemistry, Faculty of Medicine, Medical University of Lodz, Łódź, Poland
| | - Paweł Siwiński
- Department of General and Colorectal Surgery, Faculty of Military Medicine, Medical University of Lodz, Łódź, Poland
| | - Aleksandra Sobolewska-Włodarczyk
- Department of Biochemistry, Faculty of Medicine, Medical University of Lodz, Łódź, Poland; Department of Gastroenterology, Faculty of Military Medicine, Medical University of Lodz, Łódź, Poland
| | | | - Jakub Fichna
- Department of Biochemistry, Faculty of Medicine, Medical University of Lodz, Łódź, Poland
| | - Marcin Włodarczyk
- Department of Biochemistry, Faculty of Medicine, Medical University of Lodz, Łódź, Poland; Department of General and Colorectal Surgery, Faculty of Military Medicine, Medical University of Lodz, Łódź, Poland.
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Mosińska P, Jacenik D, Sałaga M, Wasilewski A, Cygankiewicz A, Sibaev A, Mokrowiecka A, Małecka-Panas E, Pintelon I, Storr M, Timmermans JP, Krajewska WM, Fichna J. FABP4 blocker attenuates colonic hypomotility and modulates white adipose tissue-derived hormone levels in mouse models mimicking constipation-predominant IBS. Neurogastroenterol Motil 2018; 30:e13272. [PMID: 29266569 DOI: 10.1111/nmo.13272] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/26/2017] [Accepted: 11/28/2017] [Indexed: 02/08/2023]
Abstract
BACKGROUND The role of fatty acid binding protein 4 (FABP4) in lower gastrointestinal (GI) motility is unknown. We aimed to verify the effect of inhibition of FABP4 on GI transit in vivo, and to determine the expression of FABP4 in mouse and human tissues. METHODS Fatty acid binding protein 4 inhibitor, BMS309403, was administered acutely or chronically for 6 and 13 consecutive days and its effect on GI transit was assessed in physiological conditions and in loperamide-induced constipation. Intracellular recordings were made to examine the effects of BMS309403 on colonic excitatory and inhibitory junction potentials. Abdominal pain was evaluated using behavioral pain response. Localization and expression of selected adipokines were determined in the mouse colon and serum using immunohistochemistry and Enzyme-Linked ImmunoSorbent Assay respectively. mRNA expression of FABP4 and selected adipokines in colonic and serum samples from irritable bowel syndrome (IBS) patients and control group were assessed. KEY RESULTS Acute injection of BMS309403 significantly increased GI motility and reversed inhibitory effect of loperamide. BMS309403 did not change colonic membrane potentials. Chronic treatment with BMS309403 increased the number of pain-induced behaviors. In the mouse serum, level of resistin was significantly decreased after acute administration; no changes in adiponectin level were detected. In the human serum, level of adiponectin and resistin, but not of FABP4, were significantly elevated in patients with constipation-IBS (IBS-C). FABP4 mRNA expression was significantly downregulated in the human colon in IBS-C. CONCLUSIONS AND INFERENCES Fatty acid binding protein 4 may be involved in IBS pathogenesis and become a novel target in the treatment of constipation-related diseases.
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Affiliation(s)
- P Mosińska
- Department of Biochemistry, Faculty of Medicine, Medical University of Lodz, Lodz, Poland
| | - D Jacenik
- Department of Cytobiochemistry, Faculty of Biology and Environmental Protection, University of Lodz, Lodz, Poland
| | - M Sałaga
- Department of Biochemistry, Faculty of Medicine, Medical University of Lodz, Lodz, Poland
| | - A Wasilewski
- Department of Biochemistry, Faculty of Medicine, Medical University of Lodz, Lodz, Poland
| | - A Cygankiewicz
- Department of Cytobiochemistry, Faculty of Biology and Environmental Protection, University of Lodz, Lodz, Poland
| | - A Sibaev
- Walter Brendel Center of Experimental Medicine, Ludwig Maximilians University of Munich, Munich, Germany
| | - A Mokrowiecka
- Department of Digestive Tract Disease, Faculty of Medicine, Medical University of Lodz, Lodz, Poland
| | - E Małecka-Panas
- Department of Digestive Tract Disease, Faculty of Medicine, Medical University of Lodz, Lodz, Poland
| | - I Pintelon
- Laboratory of Cell Biology and Histology, Department of Veterinary Sciences, University of Antwerp, Antwerp, Belgium
| | - M Storr
- Walter Brendel Center of Experimental Medicine, Ludwig Maximilians University of Munich, Munich, Germany.,Center of Endoscopy, Stanberg, Germany
| | - J P Timmermans
- Laboratory of Cell Biology and Histology, Department of Veterinary Sciences, University of Antwerp, Antwerp, Belgium
| | - W M Krajewska
- Department of Cytobiochemistry, Faculty of Biology and Environmental Protection, University of Lodz, Lodz, Poland
| | - J Fichna
- Department of Biochemistry, Faculty of Medicine, Medical University of Lodz, Lodz, Poland
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Peng YJ, Shen TL, Chen YS, Mersmann HJ, Liu BH, Ding ST. Adiponectin and adiponectin receptor 1 overexpression enhance inflammatory bowel disease. J Biomed Sci 2018; 25:24. [PMID: 29540173 PMCID: PMC5851065 DOI: 10.1186/s12929-018-0419-3] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2017] [Accepted: 02/06/2018] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND Adiponectin (ADN) is an adipokine derived from adipocytes. It binds to adiponectin receptor 1 and 2 (AdipoR1 and R2) to exert its function in regulating whole-body energy homeostasis and inflammatory responses. However, the role of ADN-AdipoR1 signaling in intestinal inflammation is controversial, and its role in the regulation of neutrophils is still unclear. Our goal was to clarify the role of AdipoR1 signaling in colitis and the effects on neutrophils. METHODS We generated porcine AdipoR1 transgenic mice (pAdipoR1 mice) and induced murine colitis using dextran sulfate sodium (DSS) to study the potential role of AdipoR1 in inflammatory bowel disease. We also treated a THP-1 macrophage and a HT-29 colon epithelial cell line with ADN recombinant protein to study the effects of ADN on inflammation. RESULTS After inducing murine colitis, pAdipoR1 mice developed more severe symptoms than wild-type (WT) mice. Treatment with ADN increased the expression of pro-inflammatory factors in THP-1 and HT-29 cells. Moreover, we also observed that the expression of cyclooxygenase2 (cox2), neutrophil chemokines (CXCL1, CXCL2 and CXCL5), and the infiltration of neutrophils were increased in the colon of pAdipoR1 mice. CONCLUSIONS Our study showed that ADN-AdipoR1 signaling exacerbated colonic inflammation through two possible mechanisms. First, ADN-AdipoR1 signaling increased pro-inflammatory factors. Second, AdipoR1 enhanced neutrophil chemokine expression and recruited neutrophils into the colonic tissue to increase inflammation.
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Affiliation(s)
- Yu-Ju Peng
- Department of Animal Science and Technology, National Taiwan University, No. 50, Ln. 155, Sec. 3, Keelung Rd., Da’an Dist, Taipei City, 10617 Taiwan
| | - Tang-Long Shen
- Department of Plant Pathology and Microbiology, National Taiwan University, No.1, Sec.4, Roosevelt Road, Taipei, 10617 Taiwan
| | - Yu-Shan Chen
- Department of Animal Science and Technology, National Taiwan University, No. 50, Ln. 155, Sec. 3, Keelung Rd., Da’an Dist, Taipei City, 10617 Taiwan
| | - Harry John Mersmann
- Department of Animal Science and Technology, National Taiwan University, No. 50, Ln. 155, Sec. 3, Keelung Rd., Da’an Dist, Taipei City, 10617 Taiwan
| | - Bing-Hsien Liu
- Department of Animal Science and Technology, National Taiwan University, No. 50, Ln. 155, Sec. 3, Keelung Rd., Da’an Dist, Taipei City, 10617 Taiwan
| | - Shih-Torng Ding
- Department of Animal Science and Technology, National Taiwan University, No. 50, Ln. 155, Sec. 3, Keelung Rd., Da’an Dist, Taipei City, 10617 Taiwan
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45
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Trejo-Vazquez F, Garza-Veloz I, Villela-Ramirez GA, Ortiz-Castro Y, Mauricio-Saucedo P, Cardenas-Vargas E, Diaz-Baez M, Cid-Baez MA, Castañeda-Miranda R, Ortiz-Rodriguez JM, Solis-Sanchez LO, Martinez-Fierro ML. Positive association between leptin serum levels and disease activity on endoscopy in inflammatory bowel disease: A case-control study. Exp Ther Med 2018; 15:3336-3344. [PMID: 29545852 PMCID: PMC5841033 DOI: 10.3892/etm.2018.5835] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2017] [Accepted: 11/17/2017] [Indexed: 12/13/2022] Open
Abstract
Inflammatory bowel disease (IBD) includes ulcerative colitis (UC), Crohn's disease (CD) and indeterminate colitis. As these subtypes of IBD display important differences in the behavior of the natural course of the disease, the identification of non-invasive markers for IBD is important. The aim of the present study was to evaluate the serum levels of 10 adipokines and their association with endoscopic activity in IBD. The 10-protein profile (C-peptide, ghrelin, gastric inhibitory polypeptide, glucagon-like peptide-1, glucagon, insulin, leptin, plasminogen activator inhibitor-1, resistin and visfatin) was evaluated using serum from 53 participants (23 UC and 11 CD patients, as well as 19 controls) from Zacatecas (Mexico) by using the Bio-Plex Pro Human Diabetes 10-Plex Panel (Bio-Rad Laboratories, Inc.). Compared with those in the controls, leptin levels were significantly lower in patients with IBD (P=4.9×10−4). In addition, serum leptin displayed differences between groups with and without disease activity on endoscopy (P<0.001). Among the study population, serum leptin levels of <5,494 pg/ml significantly increased the odds of IBD by 12.8-fold [odds ratio (OR)=12.8, 95% confidence interval (CI)=3.04–53.9, P=0.001]. In addition, patients with serum leptin levels of <2,498 pg/ml displayed 5.8-fold greater odds of disease activity on endoscopy among the study population (OR=5.8, 95% CI=1.52–22.4, P=0.013). No differences in the serum levels of the remaining proteins were identified between the groups. Among the study population, serum leptin was associated with an increased risk of IBD and with disease activity on endoscopy. Additional studies will be necessary to validate the use of leptin as a non-invasive biomarker of IBD severity.
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Affiliation(s)
- Fabiola Trejo-Vazquez
- Molecular Medicine Laboratory, Unidad Academica de Medicina Humana y Ciencias de la Salud, Universidad Autonoma de Zacatecas 'Francisco García Salinas', Zacatecas 98160, Mexico.,Department of Gastroenterology, Hospital General de Zacatecas, Instituto de Seguridad y Servicios Sociales Para Los Trabajadores del Estado, Zacatecas 98000, Mexico
| | - Idalia Garza-Veloz
- Molecular Medicine Laboratory, Unidad Academica de Medicina Humana y Ciencias de la Salud, Universidad Autonoma de Zacatecas 'Francisco García Salinas', Zacatecas 98160, Mexico.,Bioengineering Laboratory, Unidad Academica de Ingenieria Electrica, Universidad Autonoma de Zacatecas, Zacatecas 98000, Mexico
| | - Gabriela Alejandra Villela-Ramirez
- Molecular Medicine Laboratory, Unidad Academica de Medicina Humana y Ciencias de la Salud, Universidad Autonoma de Zacatecas 'Francisco García Salinas', Zacatecas 98160, Mexico.,Bioengineering Laboratory, Unidad Academica de Ingenieria Electrica, Universidad Autonoma de Zacatecas, Zacatecas 98000, Mexico
| | - Yolanda Ortiz-Castro
- Molecular Medicine Laboratory, Unidad Academica de Medicina Humana y Ciencias de la Salud, Universidad Autonoma de Zacatecas 'Francisco García Salinas', Zacatecas 98160, Mexico
| | - Panfilo Mauricio-Saucedo
- Molecular Medicine Laboratory, Unidad Academica de Medicina Humana y Ciencias de la Salud, Universidad Autonoma de Zacatecas 'Francisco García Salinas', Zacatecas 98160, Mexico.,Departamento de Enseñanza e Investigación, Hospital General Zacatecas 'Luz González Cosío', Servicios de Salud de Zacatecas, Zacatecas 98160, Mexico
| | - Edith Cardenas-Vargas
- Molecular Medicine Laboratory, Unidad Academica de Medicina Humana y Ciencias de la Salud, Universidad Autonoma de Zacatecas 'Francisco García Salinas', Zacatecas 98160, Mexico.,Departamento de Enseñanza e Investigación, Hospital General Zacatecas 'Luz González Cosío', Servicios de Salud de Zacatecas, Zacatecas 98160, Mexico
| | - Mariana Diaz-Baez
- Department of Gastroenterology, Hospital General de Zacatecas, Instituto de Seguridad y Servicios Sociales Para Los Trabajadores del Estado, Zacatecas 98000, Mexico
| | - Miguel A Cid-Baez
- Molecular Medicine Laboratory, Unidad Academica de Medicina Humana y Ciencias de la Salud, Universidad Autonoma de Zacatecas 'Francisco García Salinas', Zacatecas 98160, Mexico.,Bioengineering Laboratory, Unidad Academica de Ingenieria Electrica, Universidad Autonoma de Zacatecas, Zacatecas 98000, Mexico
| | - Rodrigo Castañeda-Miranda
- Bioengineering Laboratory, Unidad Academica de Ingenieria Electrica, Universidad Autonoma de Zacatecas, Zacatecas 98000, Mexico
| | - Jose Manuel Ortiz-Rodriguez
- Bioengineering Laboratory, Unidad Academica de Ingenieria Electrica, Universidad Autonoma de Zacatecas, Zacatecas 98000, Mexico
| | - Luis Octavio Solis-Sanchez
- Bioengineering Laboratory, Unidad Academica de Ingenieria Electrica, Universidad Autonoma de Zacatecas, Zacatecas 98000, Mexico
| | - Margarita L Martinez-Fierro
- Molecular Medicine Laboratory, Unidad Academica de Medicina Humana y Ciencias de la Salud, Universidad Autonoma de Zacatecas 'Francisco García Salinas', Zacatecas 98160, Mexico.,Bioengineering Laboratory, Unidad Academica de Ingenieria Electrica, Universidad Autonoma de Zacatecas, Zacatecas 98000, Mexico
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Kahraman R, Calhan T, Sahin A, Ozdil K, Caliskan Z, Bireller ES, Cakmakoglu B. Are adipocytokines inflammatory or metabolic mediators in patients with inflammatory bowel disease? Ther Clin Risk Manag 2017; 13:1295-1301. [PMID: 29033577 PMCID: PMC5628835 DOI: 10.2147/tcrm.s140618] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
This study examined the adiponectin and leptin levels and insulin resistance (IR) in patients with inflammatory bowel disease (IBD) and the associations between these factors and IBD characteristics. Fasting serum leptin, adiponectin, glucose, and insulin levels, as well as inflammatory parameters, were measured in 105 patients with IBD (49 patients with Crohn’s disease [CD], 56 patients with ulcerative colitis [UC]) and 98 healthy controls [HC]. IR was evaluated using the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR). Disease activity and severity in patients with UC were evaluated using the Truelove–Witts index, and patients with CD were evaluated using the Crohn’s Disease Activity Index. Serum adiponectin levels were found to be significantly lower in patients with CD and UC (p<0.001). Serum leptin levels were also found to be significantly higher in both the UC and CD groups (p<0.001). When HOMA-IR levels were compared, no significant difference was detected for either the CD or UC groups compared with the controls. In conclusion, it was shown that leptin levels increased and adiponectin levels decreased in patients with IBD, which is thought to be related to chronic inflammation. The effects of adipocytokines in patients with IBD with inflammatory and metabolic processes need to be investigated in further broader studies.
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Affiliation(s)
- Resul Kahraman
- Department of Gastroenterology, Umraniye Education and Training Hospital, Health Sciences University
| | - Turan Calhan
- Department of Gastroenterology, Umraniye Education and Training Hospital, Health Sciences University
| | - Abdurrahman Sahin
- Department of Gastroenterology, Umraniye Education and Training Hospital, Health Sciences University
| | - Kamil Ozdil
- Department of Gastroenterology, Umraniye Education and Training Hospital, Health Sciences University
| | - Zuhal Caliskan
- Department of Gastroenterology, Umraniye Education and Training Hospital, Health Sciences University
| | - Elif Sinem Bireller
- Department of Pharmaceutical Microbiology, Faculty of Pharmacy, Istanbul Yeni Yuzyil University
| | - Bedia Cakmakoglu
- Department of Molecular Medicine, Aziz Sancar Institute of Experimental Medicine, Istanbul University, Istanbul, Turkey
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Starr AE, Deeke SA, Ning Z, Chiang CK, Zhang X, Mottawea W, Singleton R, Benchimol EI, Wen M, Mack DR, Stintzi A, Figeys D. Proteomic analysis of ascending colon biopsies from a paediatric inflammatory bowel disease inception cohort identifies protein biomarkers that differentiate Crohn's disease from UC. Gut 2017; 66:1573-1583. [PMID: 27216938 PMCID: PMC5561380 DOI: 10.1136/gutjnl-2015-310705] [Citation(s) in RCA: 75] [Impact Index Per Article: 9.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/10/2015] [Revised: 03/10/2016] [Accepted: 04/25/2016] [Indexed: 12/12/2022]
Abstract
OBJECTIVE Accurate differentiation between Crohn's disease (CD) and UC is important to ensure early and appropriate therapeutic intervention. We sought to identify proteins that enable differentiation between CD and UC in children with new onset IBD. DESIGN Mucosal biopsies were obtained from children undergoing baseline diagnostic endoscopy prior to therapeutic interventions. Using a super-stable isotope labeling with amino acids in cell culture (SILAC)-based approach, the proteomes of 99 paediatric control and biopsies of patients with CD and UC were compared. Multivariate analysis of a subset of these (n=50) was applied to identify novel biomarkers, which were validated in a second subset (n=49). RESULTS In the discovery cohort, a panel of five proteins was sufficient to distinguish control from IBD-affected tissue biopsies with an AUC of 1.0 (95% CI 0.99 to 1.0); a second panel of 12 proteins segregated inflamed CD from UC within an AUC of 0.95 (95% CI 0.86 to 1.0). Application of the two panels to the validation cohort resulted in accurate classification of 95.9% (IBD from control) and 80% (CD from UC) of patients. 116 proteins were identified to have correlation with the severity of disease, four of which were components of the two panels, including visfatin and metallothionein-2. CONCLUSIONS This study has identified two panels of candidate biomarkers for the diagnosis of IBD and the differentiation of IBD subtypes to guide appropriate therapeutic interventions in paediatric patients.
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Affiliation(s)
- Amanda E Starr
- Department of Biochemistry, Microbiology and Immunology, Ottawa Institute of Systems Biology, University of Ottawa, Ottawa, Ontario, Canada
| | - Shelley A Deeke
- Department of Biochemistry, Microbiology and Immunology, Ottawa Institute of Systems Biology, University of Ottawa, Ottawa, Ontario, Canada
| | - Zhibin Ning
- Department of Biochemistry, Microbiology and Immunology, Ottawa Institute of Systems Biology, University of Ottawa, Ottawa, Ontario, Canada
| | - Cheng-Kang Chiang
- Department of Biochemistry, Microbiology and Immunology, Ottawa Institute of Systems Biology, University of Ottawa, Ottawa, Ontario, Canada
| | - Xu Zhang
- Department of Biochemistry, Microbiology and Immunology, Ottawa Institute of Systems Biology, University of Ottawa, Ottawa, Ontario, Canada
| | - Walid Mottawea
- Department of Biochemistry, Microbiology and Immunology, Ottawa Institute of Systems Biology, University of Ottawa, Ottawa, Ontario, Canada,Department of Microbiology and Immunology, Mansoura University, Mansoura, Egypt
| | - Ruth Singleton
- Children's Hospital of Eastern Ontario (CHEO) Inflammatory Bowel Disease Centre and CHEO Research Institute, University of Ottawa, Ottawa, Ontario, Canada
| | - Eric I Benchimol
- Children's Hospital of Eastern Ontario (CHEO) Inflammatory Bowel Disease Centre and CHEO Research Institute, University of Ottawa, Ottawa, Ontario, Canada,Department of Pediatrics, University of Ottawa, Ottawa, Ontario, Canada,School of Epidemiology, Public Health and Preventive Medicine, University of Ottawa, Ottawa, Ontario, Canada
| | - Ming Wen
- Department of Biochemistry, Microbiology and Immunology, Ottawa Institute of Systems Biology, University of Ottawa, Ottawa, Ontario, Canada
| | - David R Mack
- Children's Hospital of Eastern Ontario (CHEO) Inflammatory Bowel Disease Centre and CHEO Research Institute, University of Ottawa, Ottawa, Ontario, Canada,Department of Pediatrics, University of Ottawa, Ottawa, Ontario, Canada
| | - Alain Stintzi
- Department of Biochemistry, Microbiology and Immunology, Ottawa Institute of Systems Biology, University of Ottawa, Ottawa, Ontario, Canada
| | - Daniel Figeys
- Department of Biochemistry, Microbiology and Immunology, Ottawa Institute of Systems Biology, University of Ottawa, Ottawa, Ontario, Canada,Department of Chemistry and Biomolecular Sciences, University of Ottawa, Ottawa, Ontario, Canada
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48
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Janas RM, Rybak A, Wierzbicka-Rucińska A, Socha P, Śnitko R, Szaflarska-Popławska A, Stolarczyk A, Oralewska B, Cytra-Jarocka E, Iwańczak B, Grzybowska-Chlebowczyk U, Cichy W, Czaja-Bulsa G, Socha J. Serum Concentrations of Insulin, Ghrelin, Adiponectin, Leptin, Leptin Receptor and Lipocalin-2 in Children with Celiac Disease Who Do and Do Not Adhere to a Gluten-Free Diet. Gut Liver 2017; 10:587-94. [PMID: 27074817 PMCID: PMC4933420 DOI: 10.5009/gnl15404] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/19/2015] [Revised: 09/24/2015] [Accepted: 10/12/2015] [Indexed: 12/18/2022] Open
Abstract
Background/Aims The roles of the many bioactive peptides in the pathogenesis of celiac disease remain unclear. To evaluate the serum concentrations of insulin, ghrelin, adiponectin, leptin, leptin receptor, and lipocalin-2 in children with celiac disease who do and do not adhere to a gluten-free diet (GFD, intermittent adherence). Methods Prepubertal, pubertal, and adolescent celiac children were included in this study (74 girls and 53 boys on a GFD and 80 girls and 40 boys off of a GFD). Results Insulin levels in prepubertal (9.01±4.43 μIU/mL), pubertal (10.3±3.62 μIU/mL), and adolescent (10.8±4.73 μIU/mL) girls were higher than those in boys (5.88±2.02, 8.81±2.88, and 8.81±2.26 μIU/mL, respectively) and were neither age-dependent nor influenced by a GFD. Prepubertal children off of a GFD exhibited higher ghrelin levels than prepubertal children on a GFD. Adiponectin levels were not age-, sex- nor GFD-dependent. Adherence to a GFD had no effect on the expression of leptin, leptin receptor, and lipocalin-2. Conclusions Adherence to a GFD had no influence on the adiponectin, leptin, leptin receptor, and lipocalin-2 concentrations in celiac children, but a GFD decreased highly elevated ghrelin levels in prepubertal children. Further studies are required to determine whether increased insulin concentrations in girls with celiac disease is suggestive of an increased risk for hyperinsulinemia.
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Affiliation(s)
- Roman M Janas
- Department of Biochemistry, Radioimmunology and Experimental Medicine, The Children's Memorial Health Institute, Warsaw, Poland
| | - Anna Rybak
- Department of Gastroenterology, Hepatology and Nutrition Disorders, The Children's Memorial Health Institute, Warsaw, Poland
| | - Aldona Wierzbicka-Rucińska
- Department of Biochemistry, Radioimmunology and Experimental Medicine, The Children's Memorial Health Institute, Warsaw, Poland
| | - Piotr Socha
- Department of Gastroenterology, Hepatology and Nutrition Disorders, The Children's Memorial Health Institute, Warsaw, Poland
| | - Rafał Śnitko
- Department of Biochemistry, Radioimmunology and Experimental Medicine, The Children's Memorial Health Institute, Warsaw, Poland
| | - Anna Szaflarska-Popławska
- Department of Paediatric Endoscopy and Gastrointestinal Function Testing, Nicolaus Copernicus University in Toruń, Ludwik Rydygier Collegium Medicum in Bydgoszcz, Bydgoszcz, Poland
| | - Anna Stolarczyk
- Department of Gastroenterology, Hepatology and Nutrition Disorders, The Children's Memorial Health Institute, Warsaw, Poland
| | - Beata Oralewska
- Department of Gastroenterology, Hepatology and Nutrition Disorders, The Children's Memorial Health Institute, Warsaw, Poland
| | - Elżbieta Cytra-Jarocka
- Department of Pediatrics, Gastroenterology and Allergology, Medical University of Białystok, Białystok, Poland
| | - Barbara Iwańczak
- Second Department of Pediatrics, Gastroenterology and Nutrition, Medical University of Wrocław, Wrocław, Poland
| | - Urszula Grzybowska-Chlebowczyk
- Department of Pediatrics, Division of Gastroenterology, Silesian Center for Child Health, Independent Public Clinical Hospital No. 6, Medical University of Silesia, Katowice, Poland
| | - Wojciech Cichy
- First Department of Paediatric, Department of Gastroenterology and Metabolic Diseases, Poznan University of Medical Sciences, Poznań, Poland
| | - Grażyna Czaja-Bulsa
- Department of Pediatrics, Gastroenterology and Rheumatology, Pomeranian Medical University, Szczecin, Poland
| | - Jerzy Socha
- Department of Gastroenterology, Hepatology and Nutrition Disorders, The Children's Memorial Health Institute, Warsaw, Poland
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Camilleri M, Malhi H, Acosta A. Gastrointestinal Complications of Obesity. Gastroenterology 2017; 152:1656-1670. [PMID: 28192107 PMCID: PMC5609829 DOI: 10.1053/j.gastro.2016.12.052] [Citation(s) in RCA: 151] [Impact Index Per Article: 18.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/23/2016] [Revised: 12/08/2016] [Accepted: 12/12/2016] [Indexed: 12/19/2022]
Abstract
Obesity usually is associated with morbidity related to diabetes mellitus and cardiovascular diseases. However, there are many gastrointestinal and hepatic diseases for which obesity is the direct cause (eg, nonalcoholic fatty liver disease) or is a significant risk factor, such as reflux esophagitis and gallstones. When obesity is a risk factor, it may interact with other mechanisms and result in earlier presentation or complicated diseases. There are increased odds ratios or relative risks of several gastrointestinal complications of obesity: gastroesophageal reflux disease, erosive esophagitis, Barrett's esophagus, esophageal adenocarcinoma, erosive gastritis, gastric cancer, diarrhea, colonic diverticular disease, polyps, cancer, liver disease including nonalcoholic fatty liver disease, cirrhosis, hepatocellular carcinoma, gallstones, acute pancreatitis, and pancreatic cancer. Gastroenterologists are uniquely poised to participate in the multidisciplinary management of obesity as physicians caring for people with obesity-related diseases, in addition to their expertise in nutrition and endoscopic interventions.
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Affiliation(s)
- Michael Camilleri
- Clinical Enteric Neuroscience Translational and Epidemiological Research, Division of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic, Rochester, Minnesota.
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Ghomraoui FA, Alotaibi ST, Alharthi MA, Asiri SS, Almadi MA, Alharbi OR, Azzam NA, Aljebreen AM, Saeed M, Hajkhder B, Saeed W, Alzoghaibi MA. Plasma ghrelin and leptin in patients with inflammatory bowel disease and its association with nutritional status. Saudi J Gastroenterol 2017; 23:199-205. [PMID: 28611344 PMCID: PMC5470380 DOI: 10.4103/sjg.sjg_575_16] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/04/2023] Open
Abstract
BACKGROUND/AIMS Ghrelin and leptin are thought to play a role in the loss of appetite in active inflammatory bowel disease (IBD). This study seeks to probe into the association of these markers with regards to IBD and the nutritional status of these patients. A case-control study was conducted between May 2015 and March 2016 at King Khalid University Hospital (KKUH). Thirty-one patients with IBD (both active and non-active) and forty-one healthy controls (both non-fasting and fasting) were recruited. PATIENTS AND METHODS Plasma ghrelin and leptin levels were determined using an enzyme immunoassay (EIA) technique. The nutritional status was determined through the standardized Mini-Nutritional Assessment (MNA) questionnaire. RESULTS The difference in the plasma ghrelin between active (263.7 pg/mL) and non-active (108 pg/mL) cases was significant (P= 0.02). The difference in mean plasma leptin level between active cases (229.4 pg/mL) vs. non-active cases (359.7 pg/mL) was insignificant (P= 0.4). In fasting (2028.6 pg/mL) and non-fasting controls (438.8 pg/mL), the mean plasma ghrelin values was significantly different (P< 0.01). In contrast, the plasma leptin level difference between fasting (727.3 pg/mL) and non-fasting (577 pg/mL) controls was insignificant (P= 0.14). There is a statistically significant association in mean ghrelin levels between the case group and the control group (P< 0.01). With regards to nutritional status, the mean MNA score of active cases compared to fasting controls was 18.8 ± 5 vs. 20.8 ± 3.8, respectively (P< 0.01) Conclusion: Ghrelin levels were lower in the active IBD cases compared to the inactive ones, signifying an underlying pathology as etiology to this phenomenon. Furthermore, ghrelin levels were significantly lower in both case groups compared to the controls. These findings, along with the disparity in the MNA scores, insinuate a possible link between hormone levels and the loss of appetite from which these patients suffer.
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Affiliation(s)
| | - Sami T. Alotaibi
- Department of Medicine, College of Medicine, Riyadh, Saudi Arabia
| | | | - Saeed S. Asiri
- Department of Medicine, College of Medicine, Riyadh, Saudi Arabia
| | - Majid A. Almadi
- Division of Gastroenterology, McGill University Health Centre, Montreal General Hospital, Montreal, QC, Canada,Division of Gastroenterology, King Khalid University Hospital, King Saud University, Riyadh, Saudi Arabia
| | - Othman R. Alharbi
- Division of Gastroenterology, King Khalid University Hospital, King Saud University, Riyadh, Saudi Arabia
| | - Nahla A. Azzam
- Division of Gastroenterology, King Khalid University Hospital, King Saud University, Riyadh, Saudi Arabia
| | - Abdulrahman M. Aljebreen
- Division of Gastroenterology, King Khalid University Hospital, King Saud University, Riyadh, Saudi Arabia
| | - Maria Saeed
- Department of Medicine, King Khalid University Hospital, King Saud University, Riyadh, Saudi Arabia
| | - Baraa Hajkhder
- Department of Medicine, King Khalid University Hospital, King Saud University, Riyadh, Saudi Arabia
| | - Waleed Saeed
- Department of Medicine, King Khalid University Hospital, King Saud University, Riyadh, Saudi Arabia
| | - Mohammad A. Alzoghaibi
- Department of Physiology, College of Medicine, Riyadh, Saudi Arabia,Address for correspondence: Dr. Mohammad A. Alzoghaibi, College of Medicine, King Saud University, P.O Box 2925, Riyadh - 11461, Saudi Arabia. E-mail:
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