Metabolic surgery in zucker rats influenced miRNA, caveolin-1 expression and lipid metabolism

Aims: A transposition of the long segment of distal ileum in obese Zucker rats improved glucose tolerance 6 months after IT. It was undertaken to compare the gene expression of miRNA-103, -107 and caveolin-1 in the liver of euglycemic groups of IT relative to SHAM operated rats. Main methods: Obese, male Zucker rats underwent either transposition of 50% distal ileum or sham surgery. For determining the gene expression, the Real-Time PCR for caveolin-1 and miRNA-103, -107 was performed. Plasma concentrations of LDL, HDL, TG and total cholesterol were measured with enzymatic colorimetric assays after optimization procedure. Key findings: The Cav-1 expression in liver tissue after ileal transposition was 1.22 times higher compared to the SHAM group (SHAM median 63.58, min 41.3, max 82.4; IT median 77.35, min 60.8, max 95.41, p < 0.001). miRNA-107 expression was significantly downregulated by 0.6-fold in the IT group compared to the SHAM group (SHAM median 507.51, min 236.42, max 721.29; IT median 355.2, min 278.15, max 478.15, p < 0.015. The level of TG was significantly higher after IT surgery (SHAM median 115, min 96, max 143; IT median 153, min 115, max 162, p = 0.001). The total cholesterol plasma levels decreased after IT (SHAM median 178, min 161, max 183; IT median 128, min 103, max 114, p < 0.000001). The LDL plasma level in IT was two-fold lower than in the SHAM (SHAM median 117, min 68, max 151; IT median 58, min 45, max 61, p < 0.000001). Significance: The transposition of 50% of the distal ileum lead to an increase in caveolin-1 and reduction in miR-107 expression compared to those of SHAM group. Endogenous miR-107 is more involved in regulation of the functions of insulin-target liver tissue than miRNA-103. Reduced LDL and cholesterol plasma levels suggest positive effects on lipid metabolism in long-term observations. The present study is the first to show a lack of IT effect regarding triglycerides six months after surgery

Ileal transposition in rats influenced glucose metabolism and HSP70 levels

Objective: Ileal transposition procedure (IT), in combination with sleeve gastrectomy, is widely used to induce diabetes remission and to control related metabolic abnormalities. A transposition of a long segment of distal ileum in obese Zucker rats improved glucose tolerance 6 months after IT. The premise of our study was to to examine the long - term effects of ileum transposition on the liver glycolytic enzymes content in a euglycemic group of operated Zucker rats. Methods: Twenty male Zucker rats underwent either the transposition of 50% distal ileum or a sham surgery. Six months after surgery, liver tissue concentrations of glycogen synthase kinase alpha (GSK-3α), glucose 6-phosphatase (G6PC), glycogen phosphorylase (PYGM) and phosphofructokinase (PFK) and HSP70 were assessed by immunoenzymatic methods. Results: HSP70 values were significantly higher in the IT group compared to SHAM. G6PC liver concentrations in the IT group were almost 1.45-fold lower than in the SHAM operated rats. Statistical analyses (F-test) showed HSP70 levels were significantly related to caveolin-1and SHAM group. Conclusions: Lowered glycolytic enzyme concentrations assessed in the liver suggest positive effects on glucose metabolism in long-term observations

The Effects of Duodenojejunal Omega Switch in Combination with High-Fat Diet and Control Diet on Incretins, Body Weight, and Glucose Tolerance in Sprague-Dawley Rats

Background: Despite excellent results of bariatric surgery in the treatment of type 2 diabetes and weight loss in human subjects, some patients do not obtain desired results. One of the reasons for this is that not all patients follow caloric intake recommendations. Aim: The aim of this study was to investigate the effect of duodenojejunal omega switch (DJOS) surgery on body weight, glucose tolerance, and incretins in rats. Methods: DJOS and SHAM surgery were performed on rats maintained for 8 weeks on high-fat diet (HF) and control diet (CD), respectively. After surgery, four groups were kept on the same diet as before the surgery, and four groups had a changed diet (CD vs. HF and HF vs. CD) for the next 8 weeks. Glucose tolerance, insulin tolerance, glucose-stimulated insulin, glucagon-like peptide-1 (GLP-1) and gastric inhibitory polypeptide/glucose-dependent insulinotropic polypeptide (GIP) secretion, food intake, and body weight were measured. Results: A change of diet after surgery resulted in reduced glucose tolerance. Plasma insulin levels were lowered between DJOS and SHAM surgeries for the HF/HF and CD/HF groups. DJOS surgery did not reduce body weight in the studied groups, irrespective of diet. In the HF/HF group, ΔGLP-1 was lower for DJOS surgery in comparison with other groups. Differences of weight changes were observed for groups HF/HF and HF/CD. After DJOS surgery, ΔGIP was lower in the CD/HF group compared with HF/HF. Conclusions: Our results show that applications of different types of diets, before and after surgery, is a sensitive method for studies of mechanism of glucose intolerance after DJOS surgery

Neopterin and Beta-2 Microglobulin Relations to Immunity and Inflammatory Status in Nonischemic Dilated Cardiomyopathy Patients

Background. The aim of the study was to assess the relationships among serum neopterin (NPT), β2-microglobulin (β2-M) levels, clinical status, and endomyocardial biopsy results of dilated cardiomyopathy patients (DCM). Methods. Serum NPT and β-2 M were determined in 172 nonischaemic DCM patients who underwent right ventricular endomyocardial biopsy and 30 healthy subjects (ELISA test). The cryostat biopsy specimens were assessed using histology, immunohistology, and immunochemistry methods (HLA ABC, HLA DR expression, CD3 + lymphocytes, and macrophages counts). Results. The strong increase of HLA ABC or HLA DR expression was detected in 27.2% patients—group A—being low in 72.8% patients—group B. Neopterin level was increased in patients in group A compared to healthy controls 8.11 (4.50–12.57) versus 4.99 (2.66–8.28) nmol/L (P<0.05). β-2 microglobulin level was higher in DCM groups A (2.60 (1.71–3.58)) and B (2.52 (1.51–3.72)) than in the control group 1.75 (1.28–1.96) mg/L, P<0.001. Neopterin correlated positively with the number of macrophages in biopsy specimens (P<0.05) acute phase proteins: C-reactive proteins (P<0.05); fibrinogen (P<0.01); and NYHA functional class (P<0.05) and negatively with left ventricular ejection fraction (P<0.05). Conclusions. Neopterin but not β-2 microglobulin concentration reflected immune response in biopsy specimens. Neopterin correlated with acute phase proteins and stage of heart failure and may indicate a general immune and inflammatory activation in heart failure

Changes of Plasma FABP4, CRP, Leptin, and Chemerin Levels in relation to Different Dietary Patterns and Duodenal-Jejunal Omega Switch Surgery in Sprague–Dawley Rats

Background. Pathophysiological links between inflammation, obesity, and adipokines can be used for the treatment of metabolic dysregulation. Aims. To examine the influence of duodenal-jejunal omega switch surgery in combination with different diet patterns on plasma concentrations of fatty acid-binding protein 4 (FABP4), C-reactive protein (CRP), leptin, and chemerin. Methods. After 8 weeks on a high-fat diet (HF) or control diet (CD), rats underwent surgery. Duodenal-jejunal omega switch (DJOS) with an exclusion of one-third of intestinal length and SHAM surgery were performed. For the next 8 weeks, 50% of DJOS/SHAM animals were kept on the same diet as before (HF/DJOS/HF, HF/SHAM/HF, CD/DJOS/CD, and CD/SHAM/CD), and 50% had a changed diet (HF/DJOS/CD, HF/SHAM/CD, CD/DJOS/HF, and CD/SHAM/HF). FABP4, CRP, leptin, and chemerin were assessed using ELISA kits. Results. FABP4: significant differences between DJOS and SHAM were observed in animals maintained on CD/CD; CRP: varied between DJOS and SHAM groups maintained on HF/HF, CD/CD, and CD/HF; leptin and chemerin levels: DJOS lowered leptin and chemerin plasma levels versus SHAM, while HF/HF, CD/HF, and HF/CD significantly increased leptin and chemerin plasma levels when compared to CD/CD. Conclusions. The beneficial effect of DJOS surgery is stronger than proinflammatory conditions caused by an HF obesogenic diet

General, 21-Day Postoperative Rehabilitation Program Has Beneficial Effect on Oxidative Stress Markers in Patients after Total Hip or Knee Replacement

Imbalance in prooxidant-antioxidant equilibrium plays an important role in the progression of osteoarthritis (OA). Postoperative rehabilitation significantly improves the functional activity of patients with OA. We aimed to assess the effect of the general 21-day postoperative rehabilitation on the oxidative stress markers in patients after total hip arthroplasty or knee replacement. Patients (n =41) started individually designed postoperative rehabilitation ca. 90 days after endoprosthesis implantation. We used the six-minute walk test (6MWT) to quantify the changes in their exercise capacity. We analyzed the oxidative stress markers: total antioxidant capacity (TAC), total superoxide dismutase (SOD), Cu-Zn-superoxide dismutase (CuZnSOD) and ceruloplasmin (Cp) activity, malondialdehyde (MDA) and lipofuscin (LPS) concentration in patients serum to asses changes in the oxidative stress intensity. We found that after 21-days postoperative rehabilitation program: the average distance walked by patients increased by 69 m; TAC increased by 0.20 ± 0.14 mmol/l; both SOD isoforms activities increased by 1.6 (±1.7) and 1.72 (±1.5) NU/ml, respectively; but Cp activity decreased by 1.8 (0.7-3.7) mg/dl. Also, we observed lower concentrations of lipid peroxidation markers: by 19.6 ± 24.4 μmol/l for MDA and by 0.4 ± 0.5 RF for LPS. A 21-day postoperative rehabilitation program effectively reduces oxidative processes, which helps the patients after total hip or knee replacement in a successful recovery

The Effects of 21-Day General Rehabilitation after Hip or Knee Surgical Implantation on Plasma Levels of Selected Interleukins, VEGF, TNF-&alpha;, PDGF-BB, and Eotaxin-1

Rehabilitation in osteoarthritis (OA) patients aims to reduce joint pain and stiffness, preserve or improve joint mobility, and improve patients&rsquo; quality of life. This study evaluated the effects of the 21-day individually adjusted general rehabilitation program in 36 OA patients 90 days after hip or knee replacement on selected interleukins (IL) and cytokines using the Bio-Plex&reg; Luminex&reg; system. Serum concentrations of almost all selected anti/pro-inflammatory markers: IL-1 receptor antagonist (IL-1RA), IL-2, IL-4, IL-5, IL-6, IL-10, IL-13, IL-15, and of some chemokines: macrophage inflammatory protein-1 alpha (MIP-1&alpha;/CCL3), and RANTES/CCL5, and of eotaxin-1/CCL11, the vascular endothelial growth factor (VEGF) significantly increased, whereas basic fibroblast growth factor (FGF basic) significantly decreased after the 21-day general rehabilitation. The levels of interferon-&gamma; induced protein 10 (IP-10), MIP-1&beta;/CCL4, macrophage/monocyte chemoattractant protein-1 (MCP-1/CCL2 (MCAF)), granulocyte macrophage-colony stimulating factor (GM-CSF), platelet-derived growth factor-BB (PDGF-BB), and granulocyte colony-stimulating factor (G-CSF) remained unchanged. There were no changes in pro-inflammatory cytokines levels: tumor necrosis factor-alpha (TNF-&alpha;), interferon-&gamma; (IFN-&gamma;), and IL-12 (p70)) after the 21-day general rehabilitation, indicating the stable and controlled inflammatory status of osteoarthritis patients. Significantly higher levels of anti-inflammatory factors after 21 days of moderate physical activity confirm the beneficial outcome of the applied therapy. The increased level of IL-6 after the rehabilitation may reflect its anti-inflammatory effect in osteoarthritis patients

Impact of Ileal Transposition Surgical Intervention on Antioxidant Status Measured in Liver Tissue of Obese Zucker Rats (Crl:ZUC-Leprfa)

Background. The main factor characteristic for low-grade systemic inflammation typical for obesity is oxidative stress (OS). Reactive oxygen species (ROS) production is higher and more increased in time in the obese patients than in lean subjects. Aims. To assess the effect of ileal transposition (IT) and sham types of bariatric procedures on the antioxidative systems in the liver tissue of Zucker rats (Crl:ZUC Leprfa). Method. 21 animals were divided into the experimental groups: control group (n=7), sham group (n=7), and IT group (n=7). Sham and IT animals underwent selected surgery. The concentration of total antioxidant capacity (TAC), total antioxidant status (TOS), and activity of glutathione reductase (glutathione-disulfide reductase, GR, GSR), catalase (CAT), glutathione peroxidase (GPx), glutathione S-transferase (GST), and total superoxide dismutase activity (SOD) were assessed in liver tissue 3 months after surgery. Results. IT procedure significantly increased TAC when compared to sham and the control group. Animals after IT showed higher levels of TOS when compared to sham procedure. The total amount of TOS was similar in IT and control groups. GPx activity was increased in the groups submitted to the sham and IT surgery in relation to control. GR and CAT activities were significantly higher after IT in comparison to control and sham procedures. Total SOD and MnSOD were significantly higher in sham-operated animals in comparison to IT intervention and control groups. Conclusions. IT procedure had a positive impact on the diminishing of oxidative stress measured by TAC and TOS markers. The dynamic, adaptive, and protective mechanisms of enzymatic antioxidant systems were observed after the IT but not sham procedure. Nevertheless, 3 months after surgery, the midterm effect of bariatric surgery was observed, which might not fully balance the antioxidative response