Search

Background: Genetic variations in a common single nucleotide polymorphism in the ninth intron of the KIBRA gene have been linked to memory performance and risk of Alzheimer's disease (AD)., Objective: We examined the risk of AD related to presence of KIBRA T allele (versus CC homozygote) and to memory performance. The role of established genetic risk factors APOE ε4 and BDNF Met was also considered., Methods: Participants were cognitively healthy individuals (n = 19), participants with amnestic mild cognitive impairment (aMCI) due to AD (n = 99) and AD dementia (n = 37) from the Czech Brain Aging Study. Binary and multinomial logistic regressions compared odds of belonging to a certain diagnostic category and multivariate linear regressions assessed associations with memory., Results: KIBRA T allele was associated with increased AD dementia risk (odds ratio [OR] = 5.98, p  = 0.012) compared to KIBRA CC genotype. In APOE ε4 negative individuals, KIBRA T allele was associated with a greater risk of both aMCI due to AD (OR = 6.68, p  = 0.038) and AD dementia (OR = 15.75, p  = 0.009). In BDNF Met positive individuals, the KIBRA T allele was associated with a greater risk of AD dementia (OR = 10.98, p  = 0.050). In AD dementia, the association between KIBRA T allele and better memory performance approached significance (β = 0.42; p  = 0.062). The link between possessing the KIBRA T allele and better memory reached statistical significance only among BDNF Met carriers (β = 1.21, p  = 0.027)., Conclusions: Findings suggest that KIBRA T allele may not fully protect against AD dementia but could potentially delay progression of post-diagnosis cognitive deficits., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

(1) Background: C1q TNF-related protein 3 (CTRP3) is an adipokine with anti-inflammatory and cardioprotective properties. In our study, we explored changes in serum CTRP3 and its gene expression in epicardial (EAT) and subcutaneous (SAT) adipose tissue in patients with and without coronary artery disease (CAD) and type 2 diabetes mellitus (T2DM) undergoing elective cardiac surgery. (2) Methods: SAT, EAT, and blood samples were collected at the start and end of surgery from 34 patients: (i) 11 without CAD or T2DM, (ii) 14 with CAD and without T2DM, and (iii) 9 with both CAD and T2DM. mRNA levels of CTRP3 were assessed by quantitative reverse transcription PCR. Circulating levels of CTRP3 and other factors were measured using ELISA and Luminex Multiplex commercial kits. (3) Results: Baseline plasma levels of TNF-α and IL6 did not differ among the groups and increased at the end of surgery. Baseline circulating levels of CTRP3 did not differ among the groups and decreased after surgery. In contrast, baseline CTRP3 mRNA levels in EAT were significantly decreased in CAD/T2DM group, while no differences were found for TNF- α and IL6 gene expression. (4) Conclusions: Our data suggest that decreased EAT mRNA levels of CTRP3 could contribute to higher risk of atherosclerosis in patients with CAD and T2DM., Competing Interests: The authors declare no conflict of interest.

Warfarin treatment is commonly started with a fixed loading dose that might be associated with an increased risk of bleeding. An individual maintenance dose can then be estimated based on a pharmacogenetic algorithm. Starting treatment with the estimated dose implies a longer time to reach the therapeutic range. Our goal was to compare the safety and efficacy of initiating warfarin treatment with a loading dose guided by pharmacogenetics versus a maintenance dose. The primary endpoint was time in the therapeutic range (TTR) in the first 10 days of treatment. Secondary endpoints were time to the first international normalized ratio (INR) in therapeutic range (2.0-3.0) and occurrence of serious adverse events. Consenting cardioembolic stroke patients were genotyped for CYP2C9 (cytochrome P450 2C9 gene) and VKORC1 (vitamin K epoxide reductase complex, subunit 1 gene) polymorphisms and a maintenance warfarin dose was estimated. Patients were randomized into two groups. The loading dose group (LDG) patients received twice the estimated dose in the first 2 days of treatment. The maintenance dose group (MDG) patients received the estimated dose directly from day one. The TTR in the first 10 days was significantly higher in the LDG than in the MDG (50.5% vs. 38.3%, p = 0.003). The time to the first INR in this range was significantly shorter in the LDG (5.24 vs. 7.3 days). There were no significant differences in the INR above this range or serious adverse events. Warfarin loading dose guided by pharmacogenetics after recent cardioembolic stroke improved the efficacy of warfarin initiation without increasing the risk of adverse events.

Context: Neudesin has recently been identified as a novel regulator of energy expenditure in experimental animals; however, its role in humans remains unexplored., Objective: The aim of this study was to assess the effects of obesity and type 2 diabetes mellitus (T2DM) along with selected weight reducing interventions on serum neudesin levels and adipose tissue mRNA expression., Patients and Methods: Fifteen obese subjects with T2DM undergoing endoscopic duodenal-jejunal bypass liner (DJBL) implantation, 17 obese subjects (11 with T2DM, 6 without T2DM) scheduled for gastric plication (GP), 15 subjects with functional hypoglycemia subjected to 72-hour acute fasting (AF), and 12 healthy controls were included in the study., Results: Baseline neudesin levels were comparable between all groups. DJBL increased neudesin at 6 and 10 months after the procedure (1.77±0.86 vs 2.28±1.27 vs 2.13±1.02 ng/mL, P =0.001 for baseline vs 6 vs 10 months) along with reduction in body weight and improvement of HbA 1c without any effect on neudesin mRNA expression in subcutaneous adipose tissue. Conversely, GP did not affect neudesin levels despite marked reduction in body weight and improvement of HbA 1c . In contrast, AF decreased neudesin levels during the entire period (1.74±0.54 vs 1.46±0.48 ng/mL, P =0.001 for baseline vs 72 hours) with no impact of subsequent re-alimentation on neudesin concentrations., Conclusion: Neudesin levels are differentially regulated during AF and chronic weight reduction induced by DJBL or GP. Further studies are needed to assess its possible significance in energy homeostasis regulation in humans., Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Physiologically, leptin concentration is controlled by circadian rhythm. However, in critically ill patients, circadian rhythm is disrupted. Thus we hypothesized that circadian leptin concentration changes are not preserved in critically ill patients. Ten consecutive critically ill heart failure patients with the clinical indication for mechanical ventilation and sedation were included into our study. Plasma leptin concentration was measured every 4 h during the first day (0-24 h) and during the third day (48-72 h) after admission. During the first day, there were significant leptin concentration changes (ANOVA, p<0.05), characterized by an increase in concentration by 44 % (16-58 %); p=0.02 around noon (10 am-2 pm) and then a decrease in concentration by 7 % (1-27 %); p=0.04 in the morning (2 am-6 am). In contrast, there was no significant change in leptin concentration during the third day after admission (ANOVA, p=0.79). Based on our preliminary results, we concluded that in critically ill heart failure patients, the circadian rhythm of plasma leptin concentration seems to be preserved during the first but not during the third day after admission.

Aim of the Study: Angiopoietin-like protein 6 (ANGPTL6) is a circulating protein with a potential role in energy homeostasis. The aim of the study was to explore the changes in ANGPTL6 levels in patients with obesity (Body mass index, BMI > 40 kg/m 2 ) with and without type 2 diabetes mellitus (T2DM) undergoing dietary intervention (very low calorie diet - VLCD) and in a subgroup of T2DM patients after bariatric surgery. Additionally, we examined changes in ANGPTL6 in anorexia nervosa (AN) patients at baseline and after partial realimentation. We also explored the changes in ANGPTL6 mRNA expression in subcutaneous adipose tissue (SAT) of obese subjects., Materials and Methods: The study included 23 non-diabetic obese patients, 40 obese patients with T2DM (27 underwent VLCD and 13 underwent bariatric surgery), 22 patients with AN, and 37 healthy control subjects., Results: ANGPTL6 levels of AN patients were increased relative to the control group (68.6 ± 9.9 ng/ml) and decreased from 110.2 ± 13.3 to 73.6 ± 7.1 ng/ml (p = 0.004) after partial realimentation. Baseline ANGPTL6 levels in patients with obesity and T2DM did not differ from the control group. VLCD decreased ANGPTL6 levels only in obese patients with T2DM. Bariatric surgery induced a transient elevation of ANGPTL6 levels with a subsequent decrease to baseline levels. ANGPTL6 mRNA expression transiently increased after bariatric surgery and returned to baseline levels after 12 months., Conclusions: Collectively, our data suggest that serum ANGPTL6 levels and ANGPTL6 mRNA expression in SAT are affected by metabolic disorders and their treatment but do not appear to directly reflect nutritional status.

We explored the effect of chronically elevated circulating levels of growth hormone (GH)/insulin-like-growth-factor-1 (IGF-1) on mRNA expression of GH/IGF-1/insulin axis components and p85alpha subunit of phosphoinositide-3-kinase (p85alpha) in subcutaneous adipose tissue (SCAT) of patients with active acromegaly and compared these findings with healthy control subjects in order to find its possible relationships with insulin resistance and body composition changes. Acromegaly group had significantly decreased percentage of truncal and whole body fat and increased homeostasis model assessment-insulin resistance (HOMA-IR). In SCAT, patients with acromegaly had significantly increased IGF-1 and IGF-binding protein-3 (IGFBP-3) expression that both positively correlated with serum GH. P85alpha expression in SCAT did not differ from control group. IGF-1 and IGFBP-3 expression in SCAT were not independently associated with percentage of truncal and whole body fat or with HOMA-IR while IGFBP-3 expression in SCAT was an independent predictor of insulin receptor as well as of p85alpha expression in SCAT. Our data suggest that GH overproduction in acromegaly group increases IGF-1 and IGFBP-3 expression in SCAT while it does not affect SCAT p85alpha expression. Increased IGF-1 or IGFBP-3 in SCAT of acromegaly group do not appear to contribute to systemic differences in insulin sensitivity but may have local regulatory effects in SCAT of patients with acromegaly.

Background and Aims: Psoriasis vulgaris (PV) is complicated in up to 40% patients by the inflammatory joint disease psoriatic arthritis (PsA). Neither the aetiology of the arthritis nor specific laboratory markers for its disease activity have been clearly elucidated. Prolactin (PRL) acts as a cytokine with immunomodulatory functions and plays a role in skin and joint biology. The results on PRL however as a marker are unclear. The aim of this study was to confirm whether serum PRL levels reflect systemic complications of PV, like inflammatory joint disease and/or can serve as a marker of disease activity in both cases., Methods: A total of 70 patients with PV without arthritis and 40 patients suffering from PsA were included. In all patients, we determined skin disease activity according to the PASI index and in PsA, active disease assessed as swollen or tender joints. The control group included 27 age and sex matched healthy individuals. The concentration of PRL in the serum was measured by immunoradiometric assays., Results: The PRL serum levels were significantly increased in PsA patients (299.2±28.29 mIU/L) compared to PV only patients (201.4.2±11.72 mIU/L), P = 0.0003 and healthy individuals (198.2±15.31 mIU/L), P = 0.007. The serum PRL levels in PsA with active disease 336.8±42.50 (mIU/L) were higher than in PV and controls, P < 0.0001 and P = 0.002 respectively. In PV only patients, there was no correlation between PASI and PRL levels., Conclusion: Our results showed that PRL serum levels are a marker of active arthritis in PsA and reflects systemic complication rather than local skin activity.

Changes in endocrine function of adipose tissue during surgery, such as excessive production of proinflammatory cytokines, can significantly alter metabolic response to surgery and worsen its outcomes and prognosis of patients. Therapeutic hypothermia has been used to prevent damage connected with perioperative ischemia and hypoperfusion. The aim of our study was to explore the influence of deep hypothermia on systemic and local inflammation, adipose tissue hypoxia and adipocytokine production. We compared serum concentrations of proinflammatory markers (CRP, IL-6, IL-8, sIL-2R, sTNFRI, PCT) and mRNA expression of selected genes involved in inflammatory reactions (IL-6, TNF-α, MCP-1, MIF) and adaptation to hypoxia and oxidative stress (HIF1-α, MT3, GLUT1, IRS1, GPX1, BCL-2) in subcutaneous and visceral adipose tissue and in isolated adipocytes of patients undergoing cardiosurgical operation with hypothermic period. Deep hypothermia significantly delayed the onset of surgery-related systemic inflammatory response. The relative gene expression of the studied genes was not altered during the hypothermic period, but was significantly changed in six out of ten studied genes (IL-6, MCP-1, TNF-α, HIF1-α, GLUT1, GPX1) at the end of surgery. Our results show that deep hypothermia suppresses the development of systemic inflammatory response, delays the onset of local adipose tissue inflammation and thus may protect against excessive expression of proinflammatory and hypoxia-related factors in patients undergoing elective cardiac surgery procedure., (Copyright © 2014. Published by Elsevier Inc.)

Adipocyte fatty acid binding protein (A-FABP) is a novel adipokine involved in the regulation of lipid and glucose metabolism and inflammation. To evaluate its potential role in the development of postoperative hyperglycemia and insulin resistance we assessed A-FABP serum concentrations and mRNA expression in skeletal and myocardial muscle, subcutaneous and epicardial adipose tissue and peripheral monocytes in 11 diabetic and 20 age- and sex-matched non-diabetic patients undergoing elective cardiac surgery. Baseline serum A-FABP did not differ between the groups (31.1+/-5.1 vs. 25.9+/-4.6 ng/ml, p=0.175). Cardiac surgery markedly increased serum A-FABP in both groups with a rapid peak at the end of surgery followed by a gradual decrease to baseline values during the next 48 h with no significant difference between the groups at any timepoint. These trends were analogous to postoperative excursions of plasma glucose, insulin and selected proinflammatory markers. Cardiac surgery increased A-FABP mRNA expression in peripheral monocytes, while no effect was observed in adipose tissue or muscle. Our data suggest that circulating A-FABP might be involved in the development of acute perioperative stress response, insulin resistance and hyperglycemia of critically ill irrespectively of the presence of diabetes mellitus.

Appropriate differentiation capacity of adipose tissue significantly affects its ability to store lipids and to protect nonadipose tissues against lipid spillover and development of insulin resistance. Preadipocyte factor-1 (Pref-1) is an important negative regulator of preadipocyte differentiation. The aim of our study was to explore the changes in circulating Pref-1 concentrations in female subjects with obesity (OB) (n=19), females with obesity and type 2 diabetes mellitus (T2DM) (n=22), and sex- and age-matched healthy control subjects (C) (n=22), and to study its modulation by very low calorie diet (VLCD), acute hyperinsulinemia during isoglycemic-hyperinsulinemic clamp, and 3 months' treatment with PPAR-α agonist fenofibrate. At baseline, serum Pref-1 concentrations were significantly higher in patients with T2DM compared to control group, while only nonsignificant trend towards higher levels was observed in OB group. 3 weeks of VLCD decreased Pref-1 levels in both OB and T2DM group, whereas 3 months of fenofibrate treatment had no significant effect. Hyperinsulinemia during the clamp significantly suppressed Pref-1 levels in both C and T2DM subjects and this suppression was unaffected by fenofibrate treatment. In a combined population of all groups, circulating Pref-1 levels correlated positively with insulin, leptin and glucose levels and HOMA (homeostasis model assessment) index. We conclude that elevated Pref-1 concentrations in T2DM subjects may contribute to impaired adipose tissue differentiation capacity associated with insulin resistance in obese patients with T2DM. The decrease of Pref-1 levels after VLCD may be involved in the improvement of metabolic status and the amelioration of insulin resistance in T2DM patients., (© Georg Thieme Verlag KG Stuttgart · New York.)

Objective: Recent studies linked circulating pigment epithelium-derived factor (PEDF) to obesity-associated insulin resistance, but the main source of circulating PEDF is unknown. We aimed to investigate liver and adipose tissue PEDF gene expression in association with obesity and insulin resistance., Design, Subjects and Methods: Three (two cross-sectional and one longitudinal) independent cohorts have been studied, for adipose tissue (n=80 and n=30) and liver gene expression (n=32 and n=14). Effects of high glucose and cytokines on HepG2 cell line were also investigated. PEDF gene expression and circulating PEDF were analyzed using real-time PCR and ELISA, respectively., Results: In a first cohort of subjects, PEDF relative gene expression was higher in subcutaneous (SC) than in omental (OM) adipose tissue (P<0.0001) being also higher in mature adipocytes compared with stromo-vascular cells (P<0.0001). However, OM PEDF relative gene expression was decreased in morbidly obese subjects (P=0.01). Both OM PEDF and OM PEDF receptor (PEDFR) correlated positively with lipogenic and lipolytic genes, and with genes implicated in the lipid vacuole formation. Circulating PEDF levels were not associated with fat PEDF gene expression. In the second cohort, SC PEDF was decreased in subjects with type 2 diabetes and did not change significantly after weight loss. We next explored circulating PEDF in association with markers of liver-related insulin resistance injury (alanine aminotransferase, r=0.59, P=0.001). Interestingly, liver PEDF gene expression increased with obesity and insulin resistance in men, being significantly associated with fasting glucose and glycated hemoglobin in two independent cohorts. In fact, high glucose led to increased PEDF in HepG2 cells, while inflammatory stimuli present in the adipose tissue environment downregulated PEDF., Conclusion: Liver, but not adipose tissue, might be the source of increased circulating PEDF linked to insulin resistance.

We explored serum concentrations and mRNA expression of insulin-like-growth factor-1 (IGF-1) axis components in subcutaneous adipose tissue (SCAT) and peripheral monocytes (PM) of 18 healthy females, 11 obese non-diabetic females (OB) and 13 obese women with type 2 diabetes (T2DM) examined at baseline and after very-low-calorie diet (VLCD). T2DM women had decreased expression of IGF-1, IGF-1 receptor (IGF-1R), IGFBP-2 (IGF binding protein-2) and IGFBP-3 in SCAT and increased expression of IGF-1R in PM compared to control group. IGF-1R and IGFBP-3 mRNA expression in SCAT of OB was comparable to control group. In T2DM women VLCD increased serum levels and SCAT expression of IGFBP-2 and PM expression of IGFBP-3. We conclude that decreased IGF-1, IGF-1R and IGFBP-3 expression in SCAT and increased IGF-1R expression in PM of T2DM subjects might contribute to changes of fat differentiation capacity and to regulation of subclinical inflammation by PM, respectively. Increased SCAT and circulating IGFBP-2 and IGFBP-3 in PM might participate in metabolic improvements after VLCD., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Context: Low-grade inflammation links obesity, type 2 diabetes mellitus (T2DM), and cardiovascular diseases., Objective: To explore the expression profile of genes involved in inflammatory pathways in adipose tissue and peripheral monocytes (PM) of obese patients with and without T2DM at baseline and after dietary intervention., Design: Two-week intervention study with very-low-calorie diet (VLCD)., Setting: University hospital., Patients: Twelve obese females with T2DM, 8 obese nondiabetic females (OB) and 15 healthy age-matched females., Intervention: Two weeks of VLCD (2500 kJ/d)., Main Outcome Measures: Metabolic parameters, circulating cytokines, hormones, and mRNA expression of 39 genes in sc adipose tissue (SCAT) and PM., Results: Both T2DM and OB group had significantly increased serum concentrations of circulating proinflammatory factors (C-reactive protein, TNFα, IL-6, IL-8), mRNA expression of macrophage antigen CD68 and proinflammatory chemokines (CCL-2, -3, -7, -8, -17, -22) in SCAT and complementary chemokine receptors (CCR-1, -2, -3, -5) and other proinflammatory receptors (toll-like receptor 2 and 4, TNF receptor superfamily 1A and 1B, IL-6R) in PM, with OB group showing less pronounced chemoattracting and proinflammatory profile compared to T2DM group. In T2DM patients VLCD decreased body weight, improved metabolic profile, and decreased mRNA expression of up-regulated CCRs in PM and chemokines [CCL 8, chemokine (C-X-C motif) ligand 10] in SCAT. VLCD markedly increased mRNA expression of T-lymphocyte attracting chemokine CCL-17 in SCAT., Conclusion: Obese patients with and without T2DM have increased mRNA expression of chemotactic and proinflammatory factors in SCAT and expression of corresponding receptors in PM. Two weeks of VLCD significantly improved this profile in T2DM patients.

Histone deacetylase inhibitors (HDACi) are emerging new class of anticancer agents that act by inhibiting cell growth, inducing cell cycle arrest and apoptosis of various cancer cells. However, in some conditions, apoptosis can be blocked and non apoptotic cell death and irreversible growth arrest, namely senescence, can be activated as potential tumor-suppressor mechanism. Here we evaluated the dosage effects of HDAC inhibitors suberoylanilide hydroxamic acid (SAHA) and valproic acid (VPA) in a series of human leukaemia cell lines. We investigated, what concentration of SAHA and VPA can optimally induce apoptosis, growth inhibition or stress-induced premature senescence. We have found that SAHA inhibited proliferation and induced apoptosis in concentration 1000x lower than VPA. The senescence phenotype was preferentially induced by lower dosage of HDACi and required longer incubation time (5 days) while apoptosis was induced by higher dosage and appeared already after 24h. The optimal doses for the induction of cell death are 2,5-5 μM of SAHA and 2,5-5 mM of VPA. These doses of HDACi induce both apoptosis and senescence of studied leukemia cell lines.

The purpose of this study was to assess the expression profile of genes with potential role in the development of insulin resistance (adipokines, cytokines/chemokines, estrogen receptors) in subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT) and placenta of pregnant women with gestational diabetes mellitus (GDM) and age-matched women with physiological pregnancy at the time of Caesarean section. qRT-PCR was used for expression analysis of the studied genes. Leptin gene expression in VAT of GDM group was significantly higher relative to control group. Gene expressions of interleukin-6 and interleukin-8 were significantly increased, whereas the expressions of genes for estrogen receptors alpha and beta were significantly reduced in SAT of GDM group relative to controls, respectively. We found no significant differences in the expression of any genes of interest (LEP, RETN, ADIPOR1, ADIPOR2, TNF-alpha, CD68, IL-6, IL-8, ER alpha, ER beta) in placentas of women with GDM relative to controls. We conclude that increased expression of leptin in visceral adipose depot together with increased expressions of proinflammatory cytokines and reduced expressions of estrogen receptors in subcutaneous fat may play a role in the etiopathogenesis of GDM.

Objective: Fibroblast growth factor-21 (FGF21) is a novel endocrine and paracrine regulator of metabolic homeostasis. The aim of our study was to measure its serum concentrations in patients with obesity, obesity and type 2 diabetes mellitus (T2DM) and healthy subjects (C), and to assess the changes of its circulating levels and mRNA expression after dietary and pharmacological interventions., Design: We measured biochemical parameters, serum FGF21, adiponectin, leptin and insulin levels by commercial ELISA and RIA kits, and mRNA expression in the liver, subcutaneous and visceral fat by RT PCR in 26 obese patients, 11 T2DM patients and 32 control subjects. The interventions were acute hyperinsulinaemia during isoglycaemic-hyperinsulinaemic clamp, very low calorie diet (VLCD) and 3 months treatment with PPAR-alpha agonist fenofibrate., Results: Baseline serum FGF21 levels were significantly higher in both obese and T2DM patients relative to healthy controls. FGF21 levels in obesity did not significantly differ from T2DM group. Both 3 weeks of VLCD and 3 months of fenofibrate treatment significantly increased FGF21 levels. FGF21 mRNA expression in visceral fat was twofold higher in obesity relative to C group, while it did not differ in subcutaneous fat. VLCD significantly increased FGF21 mRNA expression in subcutaneous fat of obesity. 3-h hyperinsulinaemia during the clamp increased FGF21 levels in T2DM but not in C group., Conclusion: An increase in FGF21 levels after VLCD and fenofibrate treatment may contribute to positive metabolic effect of these interventions and suggests the possibility of direct positive metabolic effects of FGF21 in humans.

Objective: The number of patients with end-stage renal disease (ESRD) is rising and these patients are at higher risk of cardiovascular disease. We studied the role of hormonal production of adipose tissue in the development of chronic inflammation in patients with ESRD before kidney transplantation., Methods: Fifteen women with ESRD and 17 healthy women (control) underwent single blood drawing and visceral and subcutaneous adipose tissue sampling during surgery (kidney transplantation in the ESRD group or cholecystectomy in the control group). Serum concentrations of C-reactive protein, interleukin-6, tumor necrosis factor-alpha, leptin, adiponectin, resistin, monocyte chemoattractant protein-1 were measured. Messenger RNA expression of the same hormones, adiponectin receptors 1 and 2 and immunocompetent cell marker CD68 in subcutaneous and visceral samples were measured using real-time polymerase chain reaction. Adipose tissue was examined immunohistochemically for CD68-positive cells., Results: Serum concentrations of C-reactive protein, adiponectin, resistin, interleukin-6, tumor necrosis factor-alpha, and monocyte chemoattractant protein-1 were significantly higher in the ESRD versus control group. Subcutaneous and visceral mRNA expressions of tumor necrosis factor-alpha and CD68 were significantly increased in the ESRD versus control group. Adiponectin receptor-1 and monocyte chemoattractant protein-1 mRNA expressions were significantly higher in visceral but not in subcutaneous adipose tissue of the ESRD group. Messenger RNA expressions of resistin, leptin, adiponectin, interleukin-6, and adiponectin receptor-2 in both fat depots did not significantly differ between groups. Increased infiltration of subcutaneous and visceral adipose tissue with CD68-positive immunocompetent cells was found in the ESRD group by histologic examination., Conclusion: Subcutaneous and visceral adipose tissues in ESRD express higher amounts of proinflammatory cytokines and may play a role in the development of systemic inflammation.

Objective: Food intake is activated by hypothalamic orexigenic neuropeptide Y (NPY), which is mainly under the dual control of leptin and ghrelin. Rat adjuvant arthritis (AA), similarly as human rheumatoid arthritis, is associated with cachexia caused by yet unknown mechanisms. The aim of our study was to evaluate NPY expression in hypothalamic arcuate nuclei (nARC) under the conditions of AA-induced changes in leptin, ghrelin and adiponectin. Since IL-1beta is involved in the central induction of anorexia, we studied its expression in the nARC as well., Methods: AA was induced to Lewis rats using complete Freund's adjuvant. On days 12, 15 and 18 after complete Freund's adjuvant injection, the levels of leptin, adiponectin, ghrelin and IL-1beta were determined by RIA or ELISA. The mRNA expressions for NPY, leptin receptor (OB-R), ghrelin receptor (Ghsr) and IL-1beta were determined by TaqMan RT-PCR from isolated nARC., Results: In AA rats, decreased appetite, body mass and epididymal fat stores positively correlated with reduced circulating and epididymal fat leptin and adiponectin. Ghrelin plasma levels were increased. In nARC, mRNA for OB-R, Ghsr and NPY were overexpressed in AA rats. AA rats showed overexpression of mRNA for IL-1beta in nARC while circulating, and spleen IL-1beta was unaltered., Conclusion: During AA, overexpression of orexigenic NPY mRNA in nARC along with enhanced plasma ghrelin and lowered leptin levels occur. Decreased food intake indicates a predominant effect of the anorexigenic pathway. Activated expression of IL-1beta in nARC suggests its role in keeping AA-induced anorexia in progress. The reduction in adiponectin may also contribute to AA-induced anorexia., (Copyright 2009 S. Karger AG, Basel.)

Background: Reactive oxygen species generated by hyperglycaemia modify structure and function of lipids, proteins and other molecules taking part in chronic vascular changes in diabetes mellitus (DM). Low activity of scavenger enzymes has been observed in patients with DM. Protective role of scavenger enzymes may be deteriorated by oxidative stress. This study was undertaken to investigate the association between gene polymorphisms of selected antioxidant enzymes and vascular complications of DM., Results: Significant differences in allele and genotype distribution among T1DM, T2DM and control persons were found in SOD1 and SOD2 genes but not in CAT gene (p < 0,01). Serum SOD activity was significantly decreased in T1DM and T2DM subjects compared to the control subjects (p < 0,05). SOD1 and SOD2 polymorphisms may affect SOD activity. Serum SOD activity was higher in CC than in TT genotype of SOD2 gene (p < 0,05) and higher in AA than in CC genotype of SOD1 gene (p < 0,05). Better diabetes control was found in patients with CC than with TT genotype of SOD2 gene. Significantly different allele and genotype frequencies of SOD2 gene polymorphism were found among diabetic patients with macroangiopathy and those without it. No difference was associated with microangiopathy in all studied genes., Conclusion: The results of our study demonstrate that oxidative stress in DM can be accelerated not only due to increased production of ROS caused by hyperglycaemia but also by reduced ability of antioxidant defense system caused at least partly by SNPs of some scavenger enzymes.

Aim: Comparison of manual and automatic (MagNA Pure) isolation methods of total RNA from adipose tissue with respect to its quality and recovery factor., Material: 120 human subcutaneous adipose tissue samples (about 100 mg/sample) were collected from patients during surgical operations. The tissue sample was stabilized in RNAlater (QIAGEN GmbH, Germany)., Methods: Total RNA was extracted by the following kits: Rneasy Protect Mini, Rneasy Lipid Tissue (QIAGEN GmbH, Germany) and MagNA Pure Compact RNA Isolation (Tissue) for MagNA Pure Compact Instrument (Roche Diagnostics GmbH, Germany)., Results: The average RNA yields with Rneasy Lipid Tissue kits were about two-fold higher in comparison with the Rneasy Protect Mini kit. When the MagNA Pure Compact System was used, RNA yields from the same sample were more uniform compared with manual systems. It was also more convenient and less time-consuming than the manual approach. No DNA contamination of total RNA samples was detected except for samples isolated by Rneasy Protect Mini Kit., Conclusion: Rneasy Lipid Tissue Kit and MagNA Pure Compact RNA Isolation Kit (Tissue) provide RNA samples of high quantity, purity and PCR amplificability. RNA samples are suitable for further processing using methods of molecular biology.

Objective: To study the influence of chronic malnutrition in patients with anorexia nervosa on endocrine function of adipose tissue on both circulating and subcutaneous fat mRNA expression level., Patients and Design: A total of 12 patients with anorexia nervosa and 18 normal weight age-matched women underwent anthropometric examination, single blood drawing and subcutaneous adipose tissue biopsy., Measurements: Serum concentrations of high-sensitive CRP (hsCRP), leptin, soluble leptin receptor, adiponectin, resistin, interleukin-6 and insulin were measured by Luminex, enzyme-linked immunosorbent assay (ELISA) and radioimmunoassay (RIA) kits. Subcutaneous adipose tissue mRNA expression of the same adipokines, adiponectin receptors 1 and 2 and immunocompetent cells marker CD68 was measured by real-time polymerase chain reaction (PCR)., Results: Decreased body fat content of patients with anorexia nervosa was accompanied by reduced hsCRP, leptin and increased adiponectin and soluble leptin receptor. Resistin, interleukin-6 and insulin levels did not differ from those of the control group. Fat mRNA adiponectin, leptin, interleukin-6 and CD68 expression was reduced, resistin mRNA expression was increased and adiponectin receptor 1 and 2 expression were unchanged as compared to the control group., Conclusions: Local perturbations in resistin, adiponectin and interleukin-6 mRNA expression in subcutaneous adipose tissue are not reflected by its circulating levels. These changes could be involved in some local metabolic disturbances in subcutaneous adipose tissue of anorexia nervosa patients.

Context: Hyperglycemia and insulin resistance frequently occur in critically ill patients even without a history of diabetes., Objective: Our objective was to study the role of adipose tissue hormonal production in the development of insulin resistance in cardiac surgery patients. PARTICIPANTS, INTERVENTIONS, AND SETTINGS: Fifteen patients with elective cardiac surgery underwent blood sampling before, at the end, and 6, 12, 24, 48, and 120 h after the end of their operation. Epicardial and sc adipose tissue sampling was done at the beginning and at the end of surgery in the Department of Cardiac Surgery., Main Outcome Measures: We measured serum concentrations and sc and epicardial adipose tissue mRNA expression of IL-6, monocyte chemoattractant protein-1 (MCP-1), TNF-alpha, leptin, resistin, and adiponectin and sc and epicardial adipose tissue mRNA expression of CD14, CD45, and CD68., Results: The rate of insulin infusion required to maintain euglycemia increased up to 7-fold 12 h after the operation, suggesting the development of insulin resistance. Serum IL-6 levels increased 43-fold 12 h after surgery. MCP-1 peaked 6-fold at the end of surgery. Smaller peaks of TNF-alpha and leptin appeared 6 and 12 h after surgery, respectively. Resistin levels peaked 4-fold 24 h after surgery, but adiponectin levels were not significantly affected. TNF-alpha and CD45 mRNA expression increased markedly during the operation in sc adipose tissue. IL-6, resistin, and MCP-1 mRNA expression increased in both sc and epicardial adipose tissue. Leptin, adiponectin, CD14, and CD68 mRNA expression did not change significantly., Conclusions: Both sc and epicardial adipose tissue is a source of proinflammatory cytokines in cardiac surgery patients and may contribute to the development of postoperative insulin resistance.

We studied the effect of peroxisome proliferator-activated receptor-alpha (PPAR-alpha) activation on serum concentrations and tissue expression of resistin, adiponectin, and adiponectin receptor-1 and -2 (AdipoR1 and AdipoR2) mRNA in normal mice and mice with insulin resistance induced by lipogenic, simple-carbohydrate diet (LD). Sixteen weeks of LD feeding induced obesity with liver steatosis and increased insulin levels but did not significantly affect circulating adiponectin or resistin. Treatment with PPAR-alpha agonist fenofibrate decreased body weight and fat pad weight and ameliorated liver steatosis in LD-fed mice with concomitant reduction in blood glucose, free fatty acid, triglyceride, serum insulin levels, and homeostasis model assessment index values. Euglycemic-hyperinsulinemic clamp demonstrated the development of whole-body and liver insulin resistance in LD-fed mice, which were both normalized by fenofibrate. Fenofibrate treatment markedly increased circulating resistin levels on both diets and adiponectin levels in chow-fed mice only. Fat adiponectin mRNA expression was not affected by fenofibrate treatment. Resistin mRNA expression increased in subcutaneous but not gonadal fat after fenofibrate treatment. In addition to fat, a significant amount of adiponectin mRNA was also expressed in the muscle. This expression markedly increased after fenofibrate treatment in chow- but not in LD-fed mice. Adipose tissue expression of AdipoR1 mRNA was significantly reduced in LD-fed mice and increased after fenofibrate treatment. In conclusion, PPAR-alpha activation ameliorated the development of insulin resistance in LD-fed mice despite a major increase in serum resistin levels. This effect could be partially explained by increased AdipoR1 expression in adipose tissue after fenofibrate treatment.

Background: Growth hormone deficiency (GHD) in adult life has been associated with increased central adiposity, decreased insulin sensitivity, dyslipidaemia and increased risk of cardiovascular disease. The effects of GH replacement on adiponectin and resistin, adipokines which have a role in modulating insulin sensitivity have not been previously reported., Aim: To examine the effects of GH replacement on adipokine levels and insulin resistance in GHD patients., Design: Seventeen adult GHD patients were examined at baseline and after 1 year of treatment with recombinant human GH (mean dose 0.31 mg/day, range 0.13-0.67 mg/day)., Results: GH replacement significantly increased IGF-I levels. The mean IGF-I SD score increased from -1.98 at baseline to 0.76 at study end. GH replacement was associated with a significant reduction in percentage body fat (34.11 +/- 1.33 vs. 30.65 +/- 1.27%, P < 0.0005) and a significant increase in lean body mass (63.57 +/- 1.24 vs. 66.96 +/- 1.18%, P < 0.0004), before and after treatment, respectively. Surprisingly, there was no effect of GH replacement on the plasma levels of leptin, resistin or adiponectin or on plasma lipid profile. Insulin sensitivity did not deteriorate during GH replacement despite the known 'anti-insulin' effect of GH. Fasting glucose, insulin and insulin resistance as calculated using the homeostasis model assessment insulin resistance index (HOMA-R) were unchanged by GH treatment., Conclusion: These data demonstrate GH replacement in adult subjects with GHD is effective in changing body composition and restoring IGF-I levels over a 12-month period; however, in our study, these changes were not accompanied by changes in adipokine levels or beneficial effects on plasma lipids or insulin resistance.