The Possible Role of Adipokines in HCV Associated Hepatocellular Carcinoma

Background: Adipokines play an important role in the regulation of inflammation and tumor progression. Aim: Assessment of the possible role of adiponectin, leptin and visfatin in HCV associated hepatocellular carcinoma (HCC). Methods: patients were classified into 85 patients with HCV associated HCC, 100 patients with chronic hepatitis C viral (HCV) infection compared to 50 normal control (NC) subjects. All subjects included in the study were assessed for HCV infection by seropositive HCV antibodies, as well as HCV RNA by RT-PCR. Serum levels of adiponectin, leptin and visfatin were assessed using enzyme linked immunosorbent assay (ELISA). The data were correlated to the relevant clinic-pathological features of the patients, and the overall survival (OS) rate. Results: There was a significant difference in the serum levels of adiponectin and visfatin among HCC, HCV and NC groups (P<0.001). The serum levels of leptin and alpha fetoprotein (AFP) were significantly higher in HCC group (P<0.001). There was a significant association between the serum level of adiponectin and advanced Child class liver cirrhosis (P=0.03), as well as with poor performance status (ECOG, P=0.02). Serum leptin associated significantly with the number of lesions in the liver (P=0.006), visfatin associated with increased mortality rate (P<0.001). Adiponectin, leptin and visfatin associated significantly with liver cirrhosis in HCV patients (P<0.01). Leptin achieved the highest sensitivity (98.8%). visfatin achieved the highest specificity (100%) and PPV (100%) for detection of HCC. The combination of serum leptin and visfatin for the diagnosis of HCV associated HCC showed sensitivity, specificity, PPV, NPV and accuracy (100%, 96.6%, 93.4%, 100% and 97.4%; respectively). Conclusion: Adiponectin, leptin and visfatin have an important role(s) in the pathogenesis of HCV associated HCC.     

WJD 5~(th) Anniversary Special Issues(1): Insulin Benefits of healthy adipose tissue in the treatment of diabetes

The major malfunction in diabetes mellitus is severe perturbation of glucose homeostasis caused by deficiency of insulin.Insulin deficiency is either absolute due to destruction or failure of pancreaticβcells,or relative due to decreased sensitivity of peripheral tissues to insulin.The primary lesion being related to insulin,treatments for diabetes focus on insulin replacement and/or increasing sensitivity to insulin.These therapies have their own limitations and complications,some of which can be life-threatening.For example,exogenous insulin administration can lead to fatal hypoglycemic episodes;islet/pancreas transplantation requires life-long immunosuppressive therapy;and anti-diabetic drugs have dangerous side effects including edema,heart failure and lactic acidosis.Thus the need remains for better safer long term treatments for diabetes.The ultimate goal in treating diabetes is to re-establish glucose homeostasis,preferably through endogenously generated hormones.Recent studies increasingly show that extra-pancreatic hormones,particularly those arising from adipose tissue,can compensate for insulin,or entirely replace the function of insulin under appropriate circumstances.Adipose tissue is a versatile endocrine organ that secretes a variety of hormones with far-reaching effects on overall metabolism.While unhealthy adipose tissue can exacerbate diabetes through limiting circulation and secreting of pro-inflammatory cytokines,healthy uninflamed adipose tissue secretes beneficial adipokines with hypoglycemic and anti-inflammatory properties,which can complement and/or compensate for the function of insulin.Administration of specific adipokines is known to alleviate both type 1 and 2 diabetes,and leptin mono-therapy is reported to reverse type 1 diabetes independent of insulin.Although specific adipokines may correct diabetes,administration of individual adipokines still carries risks similar to those of insulin monotherapy.Thus a better approach is to achieve glucose homeostasis with endogenously-generated adipokines through transplantation or regeneration of healthy adipose tissue.Our recent studies on mouse models show that type 1 diabetes can be reversed without insulin through subcutaneous transplantation of embryonic brown adipose tissue,which leads to replenishment of recipients’white adipose tissue;increase of a number of beneficial adipokines;and fast and long-lasting euglycemia.Insulin-independent glucose homeostasis is established through a combination of endogenously generated hormones arising from the transplant and/or newly-replenished white adipose tissue.Transplantation of healthy white adipose tissue is reported to alleviate type 2 diabetes in rodent models on several occasions,and increasing the content of endogenous brown adipose tissue is known to combat obesity and type 2 diabetes in both humans and animal models.While the underlying mechanisms are not fully documented,the beneficial effects of healthy adipose tissue in improving metabolism are increasingly reported,and are worthy of attention as a powerful tool in combating metabolic disease.     

Adipokines in Peritoneal Dialysis: Relevant Clinical Impact According to Body Composition

Adipokines impact on clinical outcomes is not adequately addressed in peritoneal dialysis (PD). We investigated the impact of leptin/adiponectin ratio (L/A) as a predictor of cardiovascular events (CVE) in PD, taking into consideration patient's body composition and the potential role of glucose load. We prospectively followed 66 prevalent PD patients for 47.0 ± 28.2 months. New CVE were evaluated. Lean tissue index (LTI), relative fat mass (relFM) and relative overhydration (relOH) using multifrequency bioimpedance (BCM) were assessed; serum lipids, interleukin‐6 (IL‐6), leptin and adiponectin were measured. We established the determinants of L/A using multiple linear regression and the impact of L/A on CVE. Obesity was present in 47 (73.4%) patients according to relFM, and in seven (10.6%) according to body mass index (BMI). Leptin and L/A exhibited a stronger correlation with relFM (both r = 0.62, P < 0.0001) than with BMI (r = 0.46 and r = 0.51, respectively, both P < 0.0001). L/A showed a significant correlation with triglycerides (r = 0.41, P = 0.001) and HDL‐cholesterol (r = ?0.358, P = 0.003), better than isolated leptin or adiponectin. RelFM (RR = 0.130, 95%confidence interval [CI]:0.086–0.174, P < 0.0001) and LTI (RR = 0.194, 95%CI:0.037–0.351, P = 0.016) were independent predictors of L/A (R² = 0.67). Patients who suffered new CVE were older (59.12 ± 12.41 vs. 47.52 ± 13.84years, P = 0.003) and had a higher relOH (11.28 ± 7.29 vs. 6.60 ± 8.16%, P = 0.028). L/A was significantly higher in patients with CVE[2.29 (1.79) vs. 0.65 (1.73), P = 0.028] but this association was only put on evidence after excluding patients with wasting. BMI is an inaccurate method to classify obesity in PD since it underestimates its prevalence compared with body composition assessment using BCM. High adiponectin and low leptin are associated with a more favorable metabolic risk profile in peritoneal dialysis. The L/A is determined by relFM and by LTI. A higher L/A is associated with CVE in PD patients without wasting.     

脂肪因子Chemerin与膝骨性关节炎的相关性研究

目的探索膝骨性关节炎(OA)患者与正常人血清、关节液、滑膜中的脂肪因子Chemerin浓度的关系,分析其与膝OA、关节软骨损伤程度和滑膜炎症程度之间的关系。方法行关节镜手术的病人中,选取30例确诊膝OA的患者为实验组,其他膝关节疾病30例为对照组(非OA组)。采用酶联免疫吸附方法(ELISA)对关节液以及血清中脂肪因子Chemerin浓度进行测定,利用免疫组化SP法显色检测滑膜中脂肪因子Chemerin浓度。结果 OA组血清中、关节液、滑膜中脂肪因子Chemerin浓度均高于非DA组,但是2组间关节液及滑膜中脂肪因子Chemerin浓度差异有统计学意义(P<0.05)。OA组滑膜、关节液中脂肪因子浓度与患者血清中hs-CRP、Outerbridge软骨损伤评分法和Ayral滑膜炎评分法均呈正相关性。结论 OA患者血清、关节液及滑膜中均检测到脂肪因子Chemerin表达,而且其浓度与膝OA严重程度呈正相关性。     

脂肪因子与脑卒中关系的研究进展

脑卒中是神经系统常见疾病,严重危害人类健康.脑卒中相关危险因素的作用机制以及预防成为近年来研究的热点.随着生活水平的提高,肥胖已成为全球公共卫生的严重问题.脑卒中危险因素中,控制肥胖成为一种非常重要的预防手段.近年来,研究者们发现脂肪组织是一种内分泌器官,并发现了脂肪因子,为研究开辟了新的领域.大量研究证实了脂肪因子与心脑血管疾病之间的关联,发现脂肪因子作为预测指标的潜在功能.现对瘦素、脂联素、抵抗素的生理学意义以及其与脑卒中的关系进行综述.     

Effect of Non‐Surgical Periodontal Treatment on Visfatin Concentrations in Serum and Gingival Crevicular Fluid of Patients With Chronic Periodontitis and Type 2 Diabetes Mellitus

Background : This study aims to assess visfatin concentrations in serum and gingival crevicular fluid (GCF) and investigate this relationship in patients with type 2 diabetes mellitus (T2DM) and chronic periodontitis (CP) before and after non‐surgical periodontal treatment. Methods: Fifty‐four patients with T2DM and CP were recruited. The patients were randomly divided into two groups: treatment and control. Serum and GCF visfatin concentrations and glycated hemoglobin (HbA1c) levels were measured by enzyme‐linked immunosorbent assay at different time points (at baseline and 3 and 6 months after non‐surgical periodontal treatment). Results: Serum and GCF visfatin concentrations showed no significant differences between the groups at baseline (t test, P >0.05). A significant decline of visfatin in the treatment group was found in serum and GCF 3 months after non‐surgical periodontal treatment (t test, P <0.01). Baseline and 3‐month HbA1c levels were not significantly different, but at 6 months, a statistically significant difference was detected (t test, P >0.05). Conclusions: The data suggest that non‐surgical periodontal treatment is helpful for glucose control, an effect that may be associated with reduced visfatin in patients with T2DM and periodontitis. Furthermore, the data suggest that visfatin may be considered an inflammatory marker for periodontal diseases.