ABSTRACT
Background: The liver has been recognized as a major target of injury in patients with insulin resistance or the metabolic syndrome. Insulin resistance is associated with fat accumulation in the liver, a condition called nonalcoholic fatty liver disease (NAFLD). NAFLD is a clinicopathologic entity that includes a spectrum of liver damage ranging from simple steatosis to nonalcoholic steatohepatitis (NASH), advanced fibrosis, and rarely, progression to cirrhosis. Recent studies emphasize the role of insulin resistance, oxidative stress and subsequent lipid peroxidation, proinflammatory cytokines, adipokines and mitochondrial dysfunction in the development and progression of NAFLD. About 20% all adults have NAFLD and 2% to 3% of adults have NASH. A strong correlation exists between overweight, in particular visceral fat accumulation, and prevalence of NASH. Aim: "This study aimed at assessing the effect of insulin resistance in a sample of Egyptian patients with non-Alcoholic fatty liver". Methods: This study was conducted on 2 groups 104 NAFLD as diagnosed by ultrasound examination and 21 healthy participants as control group. All the participants were subjected to an abdominal ultrasonography, liver enzymes, lipid profile (triglycerides, HDL, LDL cholesterol), glucose and fasting insulin. Results: The blood sugar and fasting insulin levels were significantly higher in NAFLD patients than control group (172.81±35.47 mg/ml vs 101.33±11.95 mg/ml and11.72±4.7 U/ml vs 5.93±4.68) respectively. 88.5% of NAFLD patients were obese (BMI ≥ 30) and 11.5% were over weight (BMI < 30) while 23.8% were obese and 76.2% were overweight for control group. HOMA-IR was significantly higher in NAFLD patients than in healthy controls (5.02±2.39 vs. 1.41±1.20; P<0.001). We found 81.7% of the studied patients fulfilled the metabolic syndrome criteria while 9.5% for controls. HOMA-IR ROC curve showed 94.23% sensitivity and 85.71 specificity in NAFLD group. Fasting Insulin ROC curve showed 91.35% sensitivity and 80.95% specificity in NAFLD group. Conclusion: Patients with NAFLD have higher insulin resistance and have higher lipid profile, ALT & AST levels compared with their control group. Also the Ratio of the metabolic syndrome was higher in the NAFLD patients (81.7%).
ABSTRACT
Non alcoholic fatty liver (NAFLD) is accumulation of fat in the liver cells of peoples who drink little or no alcohol causing mild steatosis with mostly no signs, symptoms or complication but this may progress to steatohepatitis (NASH) and may liver cirrhosis then failure. NAFLD is recognized as the most common type of chronic liver disease in Western countries and the leading cause of cryptogenic cirrhosis. Insulin resistance (IR) is a key factor in the pathogenesis of NAFLD, the latter being considered as the hepatic component of IR or metabolic syndrome (MetS). Although the pathogenesis of NAFLD is not fully elucidated, a complex interaction between adipokines and cytokines produced by adipocytes and/or inflammatory cells infiltrating adipose tissue appears to play a crucial role in MetS and NAFLD and its progress. A number of factors are linked with NAFLD such as obesity, type 2 diabetis mellitus (T2DM), hyperlipidemia, gastric bypass, and its progress to NASH correlate with certain cytokines secreted like adiponectin, interlukin-6 (IL-6), and C- reactive protein CRP. Adiponectin is a novel adipocyte-specific protein, which, it has been suggested, plays a role in the development of insulin resistance and atherosclerosis. The role of (IL-6) in liver pathology is very complex, and its participation in the development of NAFLD remains unclear. IL-6 is a key element in the acute phase response, mediating the synthesis of several acute phase proteins (such as CRP and serum amyloid A). Thus, we cannot exclude the possibility that IL-6 might also play an indirect deleterious role in NAFLD pathogenesis. In diet-induced obese mice, treatment with IL-6 antibodies improved sensitivity to insulin. Objective: This study aim is to evaluate the level of adiponectin, IL-6 and CRP in Egyptian patients with NAFLD. Methods: This study was conducted on 2 groups 104 NAFLD as diagnosed by ultrasound examination and 21 healthy participants as control group. All the subjects were subjected to an abdominal ultrasonography, liver enzymes ALT & AST, lipid profile (triglycerides, HDL, LDL, cholesterol, CRP, IL-6 & Adiponectin). Results: Plasma adiponectin levels were significantly lower in NAFLD patients than control gp (3.05±2.65μg/ml vs 10.52±3.35 (μg/ml). IL-6 level was higher in NAFLD than control gp but not significant (114.24±22.32pg/ml vs 104.9±19.98pg/ml). CRP was significantly higher in NAFLD than control gp (17.86±11.59mg/L vs 5.4±3.81mg/L). Adiponectin ROC curve showed an AUROC curve in NAFLD gp (0.918 p=0.0001). IL-6 ROC curve showed an AUROC curve in NAFLD gp (0.703 p=0.0003). CRP ROC curve showed an AUROC curve in NAFLD gp (0.853 p=0.0001). Conclusion: Patients with NAFLD have lower adiponectin levels and higher IL-6 and CRP levels compared with their control group.
ABSTRACT
The present study was designed to evaluate the influence of adipose tissue derived mesenchymal stem cell (ASCs) with or without calcium phosphate composite on osteoclastogenesis in osteoporotic rats. Mesenchymal stem cells (MSCs) were harvested from adipose tissue of both the omentum and the inguinal fat pad of male rats, as the sex mismatch, to track the MSCs fate and to ensure their homing to the injured females' femurs. The isolated ASCs were characterized via the morphological appearance, multilineage potential and the PCR detection of CD29, CD44, CD106, CD14, CD34 and CD45 surface markers. Fifty adult female albino rats were enrolled in the current study. The rats were classified into five groups: group 1 was the gonad intact control, group 2 served as untreated ovariectomized (OVX) rats, group 3 was OVX rats treated with ASCs, group 4 was OVX rats treated with ASCs with injectable bone substitute (IBS) and group 5 was OVX rats treated with IBS. The serum levels of osteoprotegerin (OPG) and receptor activator of NF-қβ ligand (RANKL) were assayed using ELISA procedure. In addition, nuclear factor-κβ (NF-κβ) gene expression level was estimated in femur bones using real time –PCR. The isolated ASCs proved their MSCs identity via their morphological appearance and multilineage potential. In addition, the isolated ASCs showed positive expression for CD29, CD45, CD44 as well as CD106 and negative expression for CD34 and CD14. Besides, the positive expression of the Y-chromosome (sry) gene detected in the ASCs treated groups indicated that the systemically delivered single dose of undifferentiated ASCs was able to home at the females' femur bones. Adipose tissue derived mesenchymal stem cells (ASCs) injection with or without calcium phosphate composite in OVX rats reversed the effect of ovariectomy on the studied biomarkers causing significant increase in serum OPG level accompanied with significant decrease in serum RANKL level. Also, significant down regulation of NF-κβ gene expression in femur bones was detected in the treated groups compared with untreated OVX group. These results clarified the good influence of ASCs against osteoclastogenesis. In addition the combination of ASCs injection with osteoinductive material injectable calcium phosphate composite (IBS), may be useful to achieve the significant antiosteoporotic effects.