| 1. |
- Lohmander, L. S., et al.
(författare)
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Bariatric surgery, osteoarthritis and arthroplasty of the hip and knee in Swedish Obese Subjects - up to 31 years follow-up of a controlled intervention study.
- 2023
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Ingår i: Osteoarthritis and cartilage. - : Elsevier BV. - 1522-9653 .- 1063-4584. ; 31:5, s. 636-646
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Tidskriftsartikel (refereegranskat)abstract
- To study the long-term effect of obesity and bariatric surgery on incidences of osteoarthritis and arthroplasty of hip and knee.Hazard ratios (HR) and incidence rates (IR) of osteoarthritis and arthroplasty of hip and knee were studied in the prospective, controlled, non-randomized Swedish Obese Subjects (SOS) study (bariatric surgery group, n=2007; matched controls given usual obesity care, n=2040) and the SOS reference cohort (n=1135, general population). Osteoarthritis diagnosis and arthroplasty for osteoarthritis were captured from the National Swedish Patient Register. Median follow-up time was 21.2 (IQR 16.4-24.8), 22.9 (IQR 19.1-25.7), and 20.1 years (IQR 18.7-20.9) for the control group, surgery group and reference cohort, respectively.The surgery group displayed lower incidence of hip osteoarthritis (IR 5.3, 95% CI 4.7-6.1) compared to controls (IR 6.6, 95% CI 5.9-7.5, adjHR 0.83, 95% CI 0.69-1.00) but similar incidence of hip arthroplasty. Similar incidence of knee osteoarthritis was observed in the surgery group and controls, but knee arthroplasty was more common in the surgery group (IR 7.4, 95% CI 6.6-8.2 and 5.6, 95% CI 4.9-6.4, adjHR 1.45, 95% CI 1.22-1.74). The reference cohort displayed lower incidences of osteoarthritis and arthroplasty of hip and knee compared with the surgery group and controls.Bariatric surgery did not normalize the increased risk of knee and hip osteoarthritis in patients with obesity but was associated with an increased incidence of knee arthroplasty compared to the control group. With the limitations inherent to the present data, additional studies are needed to confirm these results.clinicaltrials.gov Identifier: NCT01479452.
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| 2. |
- Rabe, Hardis, et al.
(författare)
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Neonatal gut colonization by Bifidobacterium is associated with higher childhood cytokine responses.
- 2020
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Ingår i: Gut microbes. - : Informa UK Limited. - 1949-0984 .- 1949-0976. ; 12:1, s. 1-14
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Tidskriftsartikel (refereegranskat)abstract
- The gut microbiota is a major stimulus for the immune system, and late acquisition of bacteria and/or reduced complexity of the gut flora may delay adaptive immune maturation. However, it is unknown how the gut bacterial colonization pattern in human infants is related to T cell activation during early childhood. We followed 65 Swedish children in the FARMFLORA cohort, from birth up to 3years of age. In fecal samples collected at several time points during the first year of life, the gut colonization pattern was investigated with the use of both 16S rRNA next generation sequencing (NGS) and culture-based techniques. This was related to production of IL-13, IL-5, IL-6, TNF, IL-1β and IFN-γ by PHA-stimulated fresh mononuclear cells and to proportions of CD4+ T cells that expressed CD45RO at 36months of age. Both NGS and culture-based techniques showed that colonization by Bifidobacterium at 1week of age associated with higher production of IL-5, IL-6, IL-13, TNF and IL-1β at 36months of age. By contrast, gut colonization by Enterococcus, Staphylococcus aureus or Clostridium in early infancy related inversely to induced IL-13, IL-5 and TNF at 3years of age. Infants with elder siblings produced more cytokines and had a larger fraction of CD45RO+ T cells compared to single children. However, controlling for these factors did not abolish the effect of colonization by Bifidobacterium on immune maturation. Thus, gut colonization in early infancy affects T cell maturation and Bifidobacterium may be especially prone to induce infantile immune maturation.
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| 3. |
- Saqlain, Muhammad, et al.
(författare)
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Risk variants of obesity associated genes demonstrate BMI raising effect in a large cohort.
- 2022
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Ingår i: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 17:9
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Tidskriftsartikel (refereegranskat)abstract
- Obesity is highly polygenic disease where several genetic variants have been reportedly associated with obesity in different ethnicities of the world. In the current study, we identified the obesity risk or protective association and BMI raising effect of the minor allele of adiponectin, C1Q and collagen domain containing (ADIPOQ), cholesteryl ester transfer protein (CEPT), FTO alpha-ketoglutarate dependent dioxygenase (FTO), leptin (LEP), and leptin receptor (LEPR) genes in a large cohort stratified into four BMI-based body weight categories i.e., normal weight, lean, over-weight, and obese. Based on selected candidate genetic markers, the genotyping of all study subjects was performed by PCR assays, and genotypes and allele frequencies were calculated. The minor allele frequencies (MAFs) of all genetic markers were computed for total and BMI-based body weight categories and compared with MAFs of global and South Asian (SAS) populations. Genetic associations of variants with obesity risk were calculated and BMI raising effect per copy of the minor allele were estimated. The genetic variants with higher MAFs in obese BMI group were; rs2241766 (G = 0.43), rs17817449 (G = 0.54), rs9939609 (A = 0.51), rs1421085 (C = 0.53), rs1558902 (A = 0.63), and rs1137101 (G = 0.64) respectively. All these variants were significantly associated with obesity (OR = 1.03-4.42) and showed a high BMI raising effect (β = 0.239-0.31 Kg/m2) per copy of the risk allele. In contrast, the MAFs of three variants were higher in lean-normal BMI groups; rs3764261 A = 0.38, rs9941349 T = 0.43, and rs7799039 G = 0.40-0.43). These variants showed obesity protective associations (OR = 0.68-0.76), and a BMI lowering effect per copy of the protective allele (β = -0.103-0.155 Kg/m2). The rs3764261 variant also showed significant and positive association with lean body mass (OR = 2.38, CI = 1.30-4.34). Overall, we report six genetic variants of ADIPOQ, FTO and LEPR genes as obesity-risk markers and a CETP gene variant as lean mass/obesity protective marker in studied Pakistani cohort.
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| 4. |
- Vasileiadis, Georgios, et al.
(författare)
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Adipocytokines in Untreated Newly Diagnosed Rheumatoid Arthritis: Association with Circulating Chemokines and Markers of Inflammation
- 2021
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Ingår i: Biomolecules. - : MDPI AG. - 2218-273X. ; 11:2
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Tidskriftsartikel (refereegranskat)abstract
- Adiponectin, leptin, and resistin are adipocytokines whose levels are elevated in blood and synovial fluid from patients with rheumatoid arthritis (RA). However, their role in RA pathogenesis is unclear. Here, we examined whether adipocytokines are associated with circulating chemokines, markers of inflammation and RA disease activity in patients with untreated newly diagnosed RA. Plasma levels of 15 chemokines, adiponectin, leptin, and resistin were measured using flow cytometry bead-based immunoassay or enzyme-linked immunosorbent assay (ELISA) in a cohort of 70 patients with untreated newly diagnosed RA. Markers of inflammation and disease activity were also assessed in all patients. Positive association was found between total adiponectin and CXCL10 (beta = 0.344, p = 0.021), CCL2 (beta = 0.342, p = 0.012), and CXCL9 (beta = 0.308, p = 0.044), whereas high-molecular weight (HMW) adiponectin associated only with CXCL9 (beta = 0.308, p = 0.033). Furthermore, both total and HMW adiponectin were associated with C-reactive protein (beta = 0.485, p = 0.001; beta = 0.463, p = 0.001) and erythrocyte sedimentation rate (beta = 0.442, p = 0.001; beta = 0.507, p < 0.001). Leptin and resistin were not associated with plasma chemokines, markers of inflammation, or disease activity scores. Our study shows an association between circulating adiponectin and pro-inflammatory chemokines involved in RA pathogenesis as well as markers of inflammation in a well-characterized cohort of patients with untreated newly diagnosed RA.
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| 5. |
- Vasileiadis, Georgios, et al.
(författare)
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Adipokines and risk of rheumatoid arthritis : A two-sample multivariable Mendelian randomisation study
- 2023
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 18:6
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Tidskriftsartikel (refereegranskat)abstract
- Adiponectin, leptin, and resistin are thought to be involved in the pathogenesis of rheumatoid arthritis (RA). However, the causal relationship between these adipokines and the risk for RA is unclear. We performed a range of two-sample Mendelian randomisation (MR) analyses to assess the causal effect of circulating adiponectin, leptin, and resistin on RA risk in European and East Asian individuals. Different sets of adiponectin-, leptin-, and resistin-related genetic variants were used as instruments for genetically determined adipokine levels. As body mass index (BMI) is a risk factor for RA and affects adipokine levels, multivariable MR was used to calculate the causal effect of each adipokine on RA risk taking BMI into account. Several MR analyses revealed no evidence of a causal relationship between circulating adiponectin, leptin, or resistin levels and RA risk in either Europeans or East Asians. Similarly, multivariable MR did not provide evidence of any causal effect of adiponectin, leptin, or resistin on RA risk when taking BMI into account. This MR study shows for the first time that genetically determined levels of adiponectin, leptin, or resistin do not have a direct causal effect on the risk of developing RA after adjustment for BMI.
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| 6. |
- Zhang, Yuan, et al.
(författare)
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Adiponectin Associates with Rheumatoid Arthritis Risk in Overweight and Obesity Independently of Other Adipokines
- 2021
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Ingår i: Journal of Clinical Medicine. - : MDPI AG. - 2077-0383. ; 10:13
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Tidskriftsartikel (refereegranskat)abstract
- We recently reported that increased serum adiponectin was associated with rheumatoid arthritis (RA) risk in subjects with obesity. We hereby aim to determine if other adipokines associate with RA risk and if the association between adiponectin and RA is independent of other adipokines. Two nested-case control studies were performed in two different cohorts: 82 participants of the Swedish Obese Subjects (SOS) study who developed RA during follow-up matched with 410 controls, and 88 matched pairs from the Medical Biobank of Northern Sweden. Baseline levels of circulating adipokines were measured using ELISA. In a multivariable analysis in the SOS cohort, higher adiponectin was associated with an increased risk of RA independently of other adipokines (OR for RA risk: 1.06, 95% CI: 1.01-1.12, p = 0.02). No association between leptin, resistin, and visfatin levels and the risk of RA was detected. In the cohort from the Medical Biobank of Northern Sweden, higher adiponectin was associated with an increased risk of RA only in participants with overweight/obesity (OR: 1.17, 95% CI: 1.01-1.36, p = 0.03), independently of other adipokines. Our results show that in individuals with overweight/obesity, higher circulating levels of adiponectin, but not leptin, resistin, or visfatin, were associated with an increased RA risk.
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| 7. |
- Zhang, Y, et al.
(författare)
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Elevated adiponectin predicts the development of rheumatoid arthritis in subjects with obesity
- 2020
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Ingår i: Scandinavian Journal of Rheumatology. - : Informa UK Limited. - 0300-9742 .- 1502-7732. ; 49:6, s. 452-460
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The aim of the current study is to determine whether baseline serum adiponectin levels predict the development of rheumatoid arthritis (RA). Method: The current report includes 3693 individuals from the Swedish Obese Subjects (SOS) study. The original SOS study is a longitudinal non-randomized controlled study aiming to assess the effect of bariatric surgery on obesity-related mortality and morbidity. Participants included in the present report had adiponectin measurement available at baseline and no prevalent RA. The diagnosis of RA was retrieved through the Swedish National Patient Register. Results: During a follow-up for up to 29years, 82 study participants developed RA. Elevated baseline adiponectin levels were associated with a higher risk of developing RA independently of other factors, including C-reactive protein (CRP) and smoking [hazard ratio (HR) 1.70, 95% confidence interval (CI) 1.12–2.60 for an increase in adiponectin of 10 mg/L, p =0.01]. After stratifying the population according to adiponectin and CRP median at baseline, study participants with both adiponectin and CRP above the median had a higher risk of developing RA compared to subjects with adiponectin and CRP below the median (HR 2.80, 95% CI 1.25–6.31, p =0.01). Conclusions: In this cohort of subjects with obesity followed up for up to 29years, high serum adiponectin levels at baseline were associated with an increased risk for RA. Moreover, subjects with both high adiponectin and CRP levels at baseline were at particular risk of developing RA. ClinicalTrials.gov Identifier: NCT01479452. © 2020, © 2020 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.
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| 8. |
- Zhang, Yuan, et al.
(författare)
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Recombinant Adiponectin Induces the Production of Pro-Inflammatory Chemokines and Cytokines in Circulating Mononuclear Cells and Fibroblast-Like Synoviocytes From Non-Inflamed Subjects
- 2021
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Ingår i: Frontiers in Immunology. - : Frontiers Media SA. - 1664-3224. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- Adiponectin is an adipokine with a modulatory role in metabolism and exerting both anti- and pro-inflammatory effects. Levels of adiponectin are increased in serum and synovial fluid from patients with rheumatoid arthritis (RA). Adiponectin is able to stimulate the production of different pro-inflammatory factors from peripheral blood mononuclear cells (PBMCs) and fibroblast-like synoviocytes (FLS) from subjects with established RA. As increased circulating adiponectin levels are a risk factor for future development of RA in subjects with obesity, we hypothesize that adiponectin is implicated in the development of RA at an early stage by initiating the pro-inflammatory processes associated with the disease pathogenesis. Therefore, we aimed to determine if adiponectin is able to induce pro-inflammatory responses in cells involved in the pathogenesis of RA, but collected from subjects without any known inflammatory disease. PBMCs and FLS were obtained from non-inflamed subjects and stimulated with 5 mu g/ml human recombinant adiponectin. Supernatants collected after 48 h were analyzed for the production of 13 chemokines and 12 cytokines using multiplex assay and ELISA. Adiponectin significantly stimulated the production of CXCL1, CXCL5, and interleukin (IL)-6 in both PBMCs and FLS, whereas it induced CCL20, CCL4, CCL3, CCL17, tumor necrosis factor (TNF), granulocyte-macrophage colony-stimulating factor and IL-10 only in PBMCs, and CXCL8, CXCL10, CCL5, CCL11, and CCL2 only in FLS. Pre-stimulation with TNF of FLS from non-inflamed subjects did not significantly enhance the release of most pro-inflammatory factors compared to adiponectin alone. Our findings indicate that PBMCs and FLS from non-inflamed subjects react to adiponectin stimulation with the secretion of several pro-inflammatory chemokines and cytokines. These results suggest that adiponectin is able to initiate pro-inflammatory responses in cells from non-inflamed subjects and support the hypothesis that adiponectin is implicated in the early phases of RA pathogenesis.
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