The association of circulating levels of complement-C1q TNF-related protein 5 (CTRP5) with nonalcoholic fatty liver disease and type 2 diabetes: a case–control study (original) (raw)
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PloS one, 2015
Nonalcoholic fatty liver disease (NAFLD) is considered as one of the most common liver diseases. It is robustly linked to obesity and insulin resistance and is regarded as hepatic manifestation of metabolic syndrome (MetS). Adipokines are involved in the pathophysiology of liver diseases. The aim of this study was to evaluate the plasma concentrations of CTRP1 (complement-C1q TNF-related protein 1) in 22 patients with NAFLD, 22 patients with type 2 diabetes mellitus (T2DM), 22 patients with NAFLD+T2DM and 21 healthy controls, as well as their correlation with the level of metabolic and hepatic parameters. Plasma concentration of CTRP1 was measured with ELISA method. Plasma concentration of CTRP1 in patients with NAFLD, T2DM and NAFLD+T2DM were significantly higher than healthy subjects (p<0.0001). Moreover, we observed significant positive correlations between plasma level of CTRP1 and fasting blood glucose (FBG) (p<0.001), homeostasis model assessment of insulin resistance (H...
PloS one, 2017
The C1q complement/TNF-related protein (CTRP) superfamily, which includes the adipokine adiponectin, has been shown in animal models to have positive metabolic and cardiovascular effects. We sought to investigate circulating CTRP1, CTRP9, CTRP12 and CTRP13 concentrations in persons with type 2 diabetes mellitus (T2DM), with age and BMI matched controls, and to examine the effects of a 2 hour 75g oral glucose tolerance test (OGTT) on serum CTRP1, CTRP9, CTRP12 and CTRP13 levels in persons with T2DM. Cross-sectional study [newly diagnosed T2DM (n = 124) and control (n = 139) participants]. Serum CTRP1, CTRP9, CTRP12 and CTRP13 were measured by ELISA. Systolic and diastolic blood pressure, total cholesterol (TCH), Low-density lipoprotein (LDL)-cholesterol, triglycerides, TCH/High-density lipoprotein (HDL) ratio, triglycerides/HDL ratio, glucose, insulin, homeostatic model assessment-insulin resistance (HOMA-IR), C-reactive protein and endothelial lipase were significantly higher, where...
The Circulating CTRP13 in Type 2 Diabetes and Non-Alcoholic Fatty Liver Patients
PloS one, 2016
Numerous studies have shown that C1q/TNF-related proteins (CTRPs) are involved in the pathophysiology of metabolic disorders, such as Non-alcoholic fatty liver disease (NAFLD) and Type 2 Diabetes (T2DM). There is a little information concerning CTRP13 in the context of NAFLD and T2DM. We evaluated the plasma levels of CTRP13 in healthy control and patients with NAFLD, T2DM and NAFLD+T2DM, and also correlations between CTRP13 plasma levels and clinical and subclinical features. Circulating CTRP13 was examined in 88 male (20 healthy control, 22 T2DM patients, 22 NAFLD patients and 22 NAFLD+T2DM patients). CTRP13 and adiponectin plasma levels were measured by ELISA method. CTRP13 serum levels were higher in the control group than the other groups (all p <0.001). CTRP13 had significant negative correlation with unfavorable anthropometric and metabolic factors including BMI, visceral fat, Insulin, HOMA-IR, TG, AST, ALT and ɣ-GT and have a positive correlation with plasma concentration...
2020
Background: The C1q complement/TNF-related protein (CTRP) superfamily is a newly diagnosed adipokine with anti-inflammatory, insulin sensitivity, and glucose lowering effects. This study aimed to assess the plasma circulating levels of CTRP12 in type 2 diabetic (T2D) patients and healthy subjects. Methods: In this case-control study, plasma concentration of CTRP12 was measured by ELISA in 60 subjects (30 T2D and 30 healthy participants). The systolic blood pressure (SBP), waist circumference (WC), waist-to-hip ratio (WHR), body mass index (BMI), fasting blood sugar (FBS), glycated hemoglobin (HbA1c), insulin, and homeostasis model assessment of insulin resistance (HOMA-IR) were measured. Results:In contrast to the SBP, WC, WHR, BMI, FBS, HbA1c, insulin, and HOMA-IR, the levels of CTRP12 were significantly lower in T2D patients. There was significant negative correlation between CTRP12, FBS, and HbA1c. The regression analysis showed that when subjected to stepwise multiple regression...
Adipokines and cytokines in non-alcoholic fatty liver disease
Alimentary Pharmacology & Therapeutics, 2008
Background Several adipocytokines have been implicated in the pathogenesis nonalcoholic fatty liver disease (NAFLD). Aim To assess adipocytokines in NAFLD patients and controls. Methods A total of 95 patients (26 non-alcoholic steatohepatitis (NASH), 19 simple steatosis (SS), 38 obese controls and 12 non-obese controls) were included. Fasting serum insulin, glucose, visfatin, resistin, adiponectin, tumour necrosis factor-a (TNF-a), interleukin-8 (IL-8) and IL-6 were determined. Univariate and multivariate analyses were used to compare groups and determine associations. Results Serum TNF-a and IL-8 were higher in NAFLD patients when compared with both obese and non-obese controls. Analysis involving all patients revealed a significant correlation between serum TNF-a and IL-8 (P < 6.319e)08), and between IL-6 and IL-8 (P < 5.271e)15). Homeostatic model assessment scores negatively correlated with adiponectin in NAFLD (P < 0.0032). Serum visfatin was higher in all three obese groups than in non-obese controls (P < 0.02, P < 0.002 and P < 0.008). Visfatin in NASH patients was lower than SS and obese controls. Although TNF-a was associated with NAFLD (P < 0.02), it was interdependent on visfatin. In comparison to SS, four factors were independently associated with NASH: age, alanine aminotransferase, IL-8 and adiponectin (P < 0.05). Multivariate analysis indicated that TNF-a was the only independent predictor of fibrosis in NASH (P < 0.0004). Conclusion These findings support a complex interaction between adipocytokines and the pathogenesis of NAFLD.
Medical laboratory sciences, 2019
Background : Nonalcoholic fatty liver diseases (NAFLD) is one of the main chronic liver diseases and raises the risk of morbidity and mortality due to its inevitable outcomes. Understanding the clinical manifestations of the liver is critical to identify NAFLD patients with the greatest risk of developing nonalcoholic steatohepatitis and cirrhosis. In the liver, C1q/TNF-related protein 1 (CTRP1) modulates both glucose and lipid metabolism and improves insulin sensitivity which may affect the pathologies of the liver. Materials and Methods : This study was conducted on 22 patients with NAFLD confirmed by ultrasonography and 21 healthy subjects. Clinical and histological variables were analyzed. The ultrasonography procedure was used to quantity Common bile duct (CBD). Liver stiffness (LS) was measured by transient elastography. Res ults : There was a significant difference in CTRP1 levels between NAFLD patients and controls (p=0.032). Moreover, there was a significant positive correl...
Role of Some Adipokines in Nonalcoholic Fatty Liver Diseases
Bulletin of Egyptian Society for Physiological Sciences
Background: The prevalence of non-alcoholic fatty liver disease (NAFLD) is increasing dramatically. It is unclear why some patients develop steatohepatitis, fibrosis and cirrhosis from steatosis, while others do not. A role for adipokines has been claimed. Aim of the Study: Evaluation of serum levels of leptin, soluble leptin receptor (sOB-R), TNF-, adiponectin and insulin resistance (IR) in cases of NAFLD, and to clarify their potential role in disease progression. Subjects and Methods: The study included 60 individuals, who were divided into three equal groups; group I: Normal healthy volunteers (control subjects) with BMI (Kg/m 2) of 25.2 ±2.6; group II: Obese individuals with fatty infiltration of the liver and having normal liver functions and BMI of 31.8±1.1. Group III: Obese individuals with elevated liver functions and BMI of 32.7 ± 1.4. All groups were subjected to estimation of liver function tests, lipid profile, fasting blood glucose level, HBsAg, HCVAb and evaluation of body mass index (BMI). Serum levels of insulin, leptin, soluble leptin receptor (sOB-R), TNF-, and adiponectin were measured in all groups using ELISA technique. IR was estimated by homeostasis model assessment index ratio (HOMA-IR). Results: Serum triglycerides, insulin and HOMA-IR were significantly increased in the patients' groups, when compared to the control group. Serum levels of ALT, AST, leptin and TNF- were significantly increased, while sOB-R and serum adiponectin levels were significantly decreased in group III compared to groups I and II. Serum leptin and TNF- levels were positively correlated with BMI and HOMA-IR in groups II & III and with serum ALT and AST enzyme activity in group III, while, sOB-R levels were negatively correlated with serum leptin, TNF-, BMI and HOMA-IR in both patients' groups and with ALT and AST enzyme activity in group III. On the contrary, serum adiponectin levels were negatively correlated with BMI and HOMA-IR, serum leptin and TNF- levels in groups II & III and with both ALT and AST enzyme activity in group III. Conclusion: Measurement of serum TNF-, serum leptin and/or adiponectin may be helpful biochemical markers of NAFLD, particularly when serum AST and ALT are within normal limits.
C1q/TNF-related protein-3 (CTRP3), a novel adipokine that regulates hepatic glucose output
The Journal of biological chemistry, 2010
Adipose tissue-derived adipokines play important roles in controlling systemic insulin sensitivity and energy balance. Our recent efforts to identify novel metabolic mediators produced by adipose tissue have led to the discovery of a highly conserved family of secreted proteins, designated as C1q/TNFrelated proteins 1-10 (CTRP1 to -10). However, physiological functions regulated by CTRPs are largely unknown. Here we provide the first in vivo functional characterization of CTRP3. We show that circulating levels of CTRP3 are inversely correlated with leptin levels; CTRP3 increases with fasting, decreases in diet-induced obese mice with high leptin levels, and increases in leptin-deficient ob/ob mice. A modest 3-fold elevation of plasma CTRP3 levels by recombinant protein administration is sufficient to lower glucose levels in normal and insulin-resistant ob/ob mice, without altering insulin or adiponectin levels. The glucose-lowering effect in mice is linked to activation of the Akt signaling pathway in liver and a marked suppression of hepatic gluconeogenic gene expression. Consistent with its effects in mice, CTRP3 acts directly and independently of insulin to regulate gluconeogenesis in cultured hepatocytes. In humans, alternative splicing generates two circulating CTRP3 isoforms differing in size and glycosylation pattern. The two human proteins form hetero-oligomers, an association that does not require interdisulfide bond formation and appears to protect the longer isoform from proteolytic cleavage. Recombinant human CTRP3 also reduces glucose output in hepatocytes by suppressing gluconeogenic enzyme expression. This study provides the first functional evidence linking CTRP3 to hepatic glucose metabolism and establishes CTRP3 as a novel adipokine. . The abbreviations used are: CTRP, C1q/TNF-related protein; G6Pase, glucose-6-phosphatase; PEPCK, phosphoenolpyruvate carboxykinase; Bis-Tris, 2-[bis(2-hydroxyethyl)amino]-2-(hydroxymethyl)propane-1,3-diol; AMPK, AMP-activated protein kinase.
Role of Serum Adiponectin, IL-6 and Hs CRP in Nonalcoholic Fatty Liver Egyptian Patients
Scientific Background: 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.
Gastroenterology, 2002
Background&Aims: Nonalcoholic fatty liver disease, which can range from fatty liver alone to nonalcoholic steatohepatitis and cirrhosis, is related to insulin resistance. Tumor necrosis factor oL (TNF-eO may induce insulin resistance, and polymorphisms of its promoter have been associated with an increased release of this cytokine. We analyzed (1) the prevalence of insulin re-Sistance, (2) the prevalence of the 238 and 308 TNF-oL polymorphisms, and (3) the relationship among TNF-oL polymorphisms, insulin resistance, and the occurrence of steatohepatitis in 99 patients with nonalcoholic fatty liver diagnosed by ultrasonography and confirmed by histologic analysis in the 53 who underwent biopsy. Methods: Insulin resistance was evaluated by the homeostatic metabolic assessment insulin resistance indices and TNF-oL polymorphisms by polymerase chain reaction and restriction fragment length polymorphism analysis. Results: Insulin resistance was detected in al-t~ost all of the patients and was more severe in those With steatohepatitis. The prevalence of the 238, but not of the 308, TNF-oL polymorphism was higher in subjects with nonalcoholic fatty liver than in controls (31% vs. 15%; P < 0.0001), and patients positive for TNF-o~ polymorphisms had higher insulin resistance indices, a higher prevalence of impaired glucose tolerance, and a lower number of associated risk factors for steatosis. Conclusions: TNF-oL polymorphisms could represent a susceptibility genotype for insulin resistance, nonalcoholic fatty liver, and steatohepatitis.