Value of adipokines in predicting the severity of acute pancreatitis: Comprehensive review

AIM: To analyze the prognostic value of adipokines in predicting the course, complications and fatal outcome of acute pancreatitis (AP).METHODS: We performed the search of PubMed database and the systemic analysis of the literature for both experimental and human studies on prognostic value of adipokines in AP for period 2002-2012. Only the papers that described the use of adipokines for prediction of severity and/or complications of AP were selected for further analysis. Each article had to contain information about the levels of measured adipokines, diagnosis and verification of AP, to specify presence of pancreatic necrosis, organ dysfunction and/or mortality rates. From the very beginning, study was carried out adhering to the PRISMA checklist and flowchart for systemic reviews. To assess quality of all included human studies, the Quality Assessment of Diagnostic Accuracy Studies tool was used. Because of the high heterogeneity between the studies, it was decided to refrain from the statistical processing or meta-analysis of the available data.RESULTS: Nine human and three experimental studies were included into review. In experimental studies significant differences between leptin concentrations at 24 and 48 h in control, acute edematous and acute necrotizing pancreatitis groups were found (P = 0.027 and P < 0.001). In human studies significant differences between leptin and resitin concentrations in control and acute pancreatitis groups were found. 1-3 d serum adiponectin threshold of 4.5 μg/mL correctly classified the severity of 81% of patients with AP. This threshold yielded a sensitivity of 70%, specificity 85%, positive predictive value 64%, negative predictive value88% (area under curve 0.75). Resistin and visfatin concentrations differ significantly between mild and severe acute pancreatitis groups, they correlate with severity of disease, need for interventions and outcome. Both adipokines are good markers for parapancreatic necrosis and the cut-off values of 11.9 ng/mL and 1.8 ng/mL respectively predict the high ranges of radiological scores. However, the review revealed that all nine human studies with adipokines are very different in terms of methodology and objectives, so it is difficult to generalize their results. It seems that concentrations of the leptin and resistin increases significantly in patients with acute pancreatitis compared with controls. Serum levels of adiponectin, visfatin and especially resitin (positive correlation with Acute Physiology and Chronic Health Evaluation II, Ranson and C-reactive protein) are significantly different in mild acute pancreatitis and severe acute pancreatitis patients, so, they can serve as a markers for the disease severity prediction. Resistin and visfatin can also be used for pancreatic and parapancreatic necrosis prediction, interventions needs and possible, outcome.CONCLUSION: High levels of adipokines could allow for prediction of a severe disease course and outcome even in small pancreatic lesions on computed tomography scans.     

NGAL与妊娠相关疾病的研究进展

中性粒细胞明胶酶相关脂质运载蛋白（neutrophil gelatinase-associated lipocalin,NGAL）作为脂质运载蛋白lipocalin家族的新成员,是一种脂肪细胞因子,亦是一种炎症因子。NGAL在机体中参与不同的生理、病理过程,涉及胚胎发育、细胞分化、细胞凋亡、肿瘤的发生及发展、炎症免疫反应、糖脂代谢及胰岛素抵抗等。妊娠期高血压疾病、妊娠期糖尿病（gestational diabetes mellitus,GDM）及早产等是常见的妊娠相关疾病,其发生、发展与机体的炎症反应、糖脂代谢及胰岛素抵抗关系密切,这些疾病严重影响妊娠结局和母婴的预后情况。NGAL的生物学功能使其在妊娠期高血压疾病、GDM及早产等妊娠相关疾病中亦发挥重要作用。本文对NGAL及其与妊娠相关疾病的研究进展进行综述。     

Central obesity and altered peripheral adipose tissue gene expression characterize the NAFLD patient with insulin resistance: Role of nutrition and insulin challenge

ObjectiveInsulin resistance (IR) and white adipose tissue (WAT) dysfunction frequently are associated with nonalcoholic fatty liver disease (NAFLD); however, the pathogenic mechanisms contributing to their clustering are not well defined. The aim of this study was to define some nutritional, anthropometric, metabolic, and genetic mechanisms contributing to their clustering.MethodsForty-five (20 men, 25 women) patients (age 45.7 ± 11.1 y) with recent diagnosis of NAFLD were grouped according to IR state. Energy balance was assessed using a food questionnaire and indirect calorimetry, and body composition with anthropometry and dual-energy x-ray absorptiometry. Biochemical and hormonal parameters combined with adipose tissue gene expression were determined. Microarray analysis of gene expression was performed in a subset of WAT samples from IR patients (n = 9), in the fasted state, after specific test meals (monounsaturated fatty acid [MUFA], saturated fat [SAT], and carbohydrate-rich) and after being challenged with insulin.ResultsIR patients exhibited higher trunk fat to leg fat ratio (P < 0.05) and had a higher ratio of SAT/MUFA fat intake (P < 0.05) than insulin-sensitive (IS) individuals. Deposition of fat in the trunk but not in the leg was directly related to liver enzyme levels (P < 0.05). IR patients also had lower adiponectin serum levels and leptin (LEP) mRNA expression in WAT compared with IS patients (P < 0.01 and P < 0.05, respectively). Microarray analysis after insulin challenge confirmed that insulin treatment induces the expression of PPARG gene and LEP and decreases GCGR gene (P < 0.05 for all) in WAT. No changes in these genes were observed in the postprandial state induced after the acute effect of specific diets.ConclusionsPatients exhibiting NAFLD and IR had preferential central fat deposition directly related to their serum alanine aminotransferase levels. These patients showed peripheral adipose tissue dysfunction and exhibited inappropriately low LEP biosynthesis that could be partially restored after anabolic conditions induced by insulin signaling.     

Concentration of adipogenic and proinflammatory cytokines in the bone marrow supernatant fluid of osteoporotic women

Osteoporosis is characterized by low bone mass, microarchitectural deterioration of bone tissue leading to increased bone fragility, and a resulting susceptibility to fractures. Distinctive environmental bone marrow conditions appear to support the development and maintenance of the unbalance between bone resorption and bone formation; these complex bone marrow circumstances would be reflected in the fluid surrounding bone marrow cells. The content of regulatory molecules in the extracellular fluid from the human bone marrow is practically unknown. Since the content of cytokines such as adiponectin, leptin, osteoprogeterin (OPG), soluble receptor activator of nuclear factor κB ligand (s‐RANKL), tumor necrosis factor α, and interleukin 6 (IL‐6) may elicit conditions promoting or sustaining osteoporosis, in this work we compared the concentrations of the above‐mentioned cytokines and also the level of the soluble receptors for both IL‐6 and leptin in the extracellular fluid from the bone marrow of nonosteoporotic and osteoporotic human donors. A supernatant fluid (bone marrow supernatant fluid [BMSF]) was obtained after spinning the aspirated bone marrow samples; donors were classified as nonosteoporotic or osteoporotic after dual‐energy X‐ray absorptiometry (DXA) measuring. Specific commercially available kits were used for all measurements. The cytokines' concentration in BMSF showed differently among nonosteoporotic and osteoporotic women; this last group was characterized by higher content of proinflammatory and adipogenic cytokines. Also, osteoporotic BMSF differentiated by decreased leptin bioavailability, suggesting that insufficient leptin action may distinguish the osteoporotic bone marrow. © 2010 American Society for Bone and Mineral Research     

血清脂肪因子与代谢综合征的关系

121例代谢综合征(MS)患者和120名对照者入选本研究以探讨血清脂肪因子与MS的关系.对照组、非腹型肥胖MS组及腹型肥胖MS组的血清抵抗素和脂肪细胞型脂肪酸结合蛋白(A-FABP)依次增高,而脂联素水平依次降低(均P<0.05).MS组抵抗素与体重指数(BMI)、腰围、收缩压、空腹血糖和A-FABP呈正相关(P<0.05或P<0.01);脂联素与高密度脂蛋白胆固醇呈正相关,而与BMI、腰围、空腹胰岛素、甘油三酯、稳态模型评估的胰岛素抵抗指数(HOMA-IR)呈负相关.     

阻塞性睡眠呼吸暂停与脂肪因子

阻塞性睡眠呼吸暂停是一种常见的睡眠呼吸障碍,伴随着严重的医学及心理学方面的并发症。肥胖,特别是腹型肥胖,是阻塞性睡眠呼吸暂停的主要危险因素,肥胖患者的脂肪组织可分泌多种脂肪因子和炎性因子,如瘦素、脂联素和抵抗素等。现就阻塞性睡眠呼吸暂停患者脂肪因子水平的变化及新近发现的一些脂肪因子予以综述,探讨阻塞性睡眠呼吸暂停与脂肪因子的可能关系。     

Retinol-binding protein 4 is associated with components of the metabolic syndrome, but not with insulin resistance, in men with type 2 diabetes or coronary artery disease

Aims/hypothesis Retinol-binding protein 4 (RBP4) has recently been reported to be associated with insulin resistance and the metabolic syndrome. This study tested the hypothesis that RBP4 is a marker of insulin resistance and the metabolic syndrome in patients with type 2 diabetes or coronary artery disease (CAD) or in non-diabetic control subjects without CAD. Methods Serum RBP4 was measured in 365 men (126 with type 2 diabetes, 143 with CAD and 96 control subjects) and correlated with the homeostasis model assessment of insulin resistance index (HOMA-IR), components of the metabolic syndrome and lipoprotein metabolism. RBP4 was detected by ELISA and validated by quantitative Western blotting. Results RBP4 concentrations detected by ELISA were shown to be strongly associated with the results gained in quantitative Western blots. There were no associations of RBP4 with HOMA-IR or HbA_1c in any of the groups studied. In patients with type 2 diabetes there were significant positive correlations of RBP4 with total cholesterol, LDL-cholesterol, VLDL-cholesterol, plasma triacylglycerol and hepatic lipase activity. In patients with CAD, there were significant associations of RBP4 with VLDL-cholesterol, plasma triacylglycerol and hepatic lipase activity, while non-diabetic control subjects without CAD showed positive correlations of RBP4 with VLDL-cholesterol and plasma triacylglycerol. Conclusions/interpretation RBP4 does not seem to be a valuable marker for identification of the metabolic syndrome or insulin resistance in male patients with type 2 diabetes or CAD. Independent associations of RBP4 with pro-atherogenic lipoproteins and enzymes of lipoprotein metabolism indicate a possible role of RBP4 in lipid metabolism.     

Adiponectin complexes in human cerebrospinal fluid: distinct complex distribution from serum

Aims/hypothesis Adiponectin is an adipocyte-derived secretory factor that is specifically produced in adipocytes. It exerts effects on energy homeostasis via peripheral and central mechanisms. However, it is not clear whether adiponectin crosses the blood–brain barrier in humans. In serum, adiponectin circulates in several different complexes, each of which has distinct functions. Here, we wanted to test whether adiponectin can be found in human cerebrospinal fluid (CSF) and whether specific adiponectin complexes are enriched in CSF compared with peripheral serum samples. We also wanted to establish whether there is a sex-related difference with regard to the distribution of adiponectin oligomers in CSF. Materials and methods We studied 22 subjects (11 men, 11 women) in this study. Their average BMI was 28.0 ± 4.7 kg/m²; average age was 70 ± 7 years. Results Analysis of total adiponectin revealed that adiponectin protein is present in human CSF at approximately 0.1% of serum concentration. The distribution of adiponectin oligomers differs considerably in CSF from that of serum within matched samples from the same patients. Only the adiponectin trimeric and low-molecular-mass hexameric complexes are found in CSF, with a bias towards the trimeric form in most patients. Male subjects have a higher CSF:serum ratio of total adiponectin (p < 0.05; n = 20) and have slightly higher trimer levels in serum and CSF than female subjects. Conclusions/interpretation We conclude that the adiponectin trimer is the predominant oligomer in human CSF.