Whey Protein Combined with Low Dietary Fiber Improves Lipid Profile in Subjects with Abdominal Obesity: A Randomized, Controlled Trial

Abdominal obesity is associated with elevated postprandial triglycerides (TG), an independent risk factor for cardiovascular diseases. Previous studies show that whey protein (WP) and dietary fiber may separately reduce postprandial TG. However, few studies have investigated the long-term effects of WP and dietary fiber on postprandial TG. We aimed to investigate the separate and combined long-term effects of WP and dietary fiber from wheat bran on postprandial TG and markers of lipid metabolism in subjects with abdominal obesity. We conducted a 12-week, double-blind, randomized, controlled, parallel intervention study. In a 2 7 2 factorial design, 73 adults were randomized to receive 60 g/day of either WP hydrolysate or maltodextrin (MD) combined with high-fiber wheat bran products (HiFi; 30 g dietary fiber/day) or low-fiber refined wheat products (LoFi; 10 g dietary fiber/day). A high-fat meal test was conducted before and after the intervention. Sixty-five subjects were included in the final analyses. There were no differences between intervention groups in postprandial TG assessed as incremental area under the curve (iAUC). WP-LoFi had reduced postprandial TG assessed as total area under the curve (tAUC) and reduced fasting TG compared with all other groups, and reduced fasting apolipoprotein B-48 compared with MD-LoFi. There were no changes in lipoprotein lipase activity. Total cholesterol and apolipoprotein B-100 were reduced after WP intake compared with MD. Total cholesterol was increased after HiFi intake compared with LoFi. In conclusion, intake of WP in combination with low-fiber cereal products for 12 weeks had beneficial effects on postprandial TG tAUC and fasting TG, but not on postprandial TG iAUC in subjects with abdominal obesity. Combining WP with high-fiber wheat bran products did not improve lipid profile

Reversible insulin resistance in muscle and fat unrelated to the metabolic syndrome in patients with acromegaly

BACKGROUND: Patients with active acromegaly exhibit insulin resistance despite a lean phenotype whereas controlled disease improves insulin sensitivity and increases fat mass. The mechanisms underlying this paradox remain elusive, but growth hormone (GH)-induced lipolysis plays a central role. The aim of the study was to investigative the molecular mechanisms of insulin resistance dissociated from obesity in patients with acromegaly. METHODS: In a prospective study, twenty-one patients with newly diagnosed acromegaly were studied at diagnosis and after disease control obtained by either surgery alone (n=10) or somatostatin analogue (SA) treatment (n=11) with assessment of body composition (DXA scan), whole body and tissue-specific insulin sensitivity and GH and insulin signalling in adipose tissue and skeletal muscle. FINDINGS: Disease control of acromegaly significantly reduced lean body mass (p<0.001) and increased fat mass (p<0.001). At diagnosis, GH signalling (pSTAT5) was constitutively activated in fat and enhanced expression of GH-regulated genes (CISH and IGF-I) were detected in muscle and fat. Insulin sensitivity in skeletal muscle, liver and adipose tissue increased after disease control regardless of treatment modality. This was associated with enhanced insulin signalling in both muscle and fat including downregulation of phosphatase and tensin homolog (PTEN) together with reduced signalling of GH and lipolytic activators in fat. INTERPRETATION: In conclusion, the study support that uncontrolled lipolysis is a major feature of insulin resistance in active acromegaly, and is characterized by upregulation of PTEN and suppression of insulin signalling in both muscle and fat. FUNDING: This work was supported by a grant from the Independent Research Fund, Denmark (7016-00303A) and from the Alfred Benzon Foundation, Denmark

Pleiotropic Effects of Influenza Vaccination

Influenza vaccines are designed to mimic natural influenza virus exposure and stimulate a long-lasting immune response to future infections. The evolving nature of the influenza virus makes vaccination an important and efficacious strategy to reduce healthcare-related complications of influenza. Several lines of evidence indicate that influenza vaccination may induce nonspecific effects, also referred to as heterologous or pleiotropic effects, that go beyond protection against infection. Different explanations are proposed, including the upregulation and downregulation of cytokines and epigenetic reprogramming in monocytes and natural killer cells, imprinting an immunological memory in the innate immune system, a phenomenon termed “trained immunity”. Also, cross-reactivity between related stimuli and bystander activation, which entails activation of B and T lymphocytes without specific recognition of antigens, may play a role. In this review, we will discuss the possible nonspecific effects of influenza vaccination in cardiovascular disease, type 1 diabetes, cancer, and Alzheimer’s disease, future research questions, and potential implications. A discussion of the potential effects on infections by other pathogens is beyond the scope of this review

Increased levels of IgG antibodies against human HSP60 in patients with spondyloarthritis

<div><p>Spondyloarthritis (SpA) comprises a heterogeneous group of inflammatory diseases, with strong association to human leukocyte antigen (HLA)-B27. A triggering bacterial infection has been considered as the cause of SpA, and bacterial heat shock protein (HSP) seems to be a strong T cell antigen. Since bacterial and human HSP60, also named HSPD1, are highly homologous, cross-reactivity has been suggested in disease initiation. In this study, levels of antibodies against bacterial and human HSP60 were analysed in SpA patients and healthy controls, and the association between such antibodies and disease severity in relation to HLA-B27 was evaluated.</p><p>Serum samples from 82 patients and 50 controls were analysed by enzyme-linked immunosorbent assay (ELISA) for immunoglobulin (Ig)G1, IgG2, IgG3 and IgG4 antibodies against human HSP60 and HSP60 from <i>Chlamydia trachomatis, Salmonella enteritidis</i> and <i>Campylobacter jejuni</i>. Disease severity was assessed by the clinical scorings Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI) and Bath Ankylosing Spondylitis Metrology Index (BASMI).</p><p>Levels of IgG1 and IgG3 antibodies against human HSP60, but not antibodies against bacterial HSP60, were elevated in the SpA group compared with the control group. Association between IgG3 antibodies against human HSP60 and BASMI was shown in HLA-B27⁺ patients. Only weak correlation between antibodies against bacterial and human HSP60 was seen, and there was no indication of cross-reaction.</p><p>These results suggest that antibodies against human HSP60 is associated with SpA, however, the theory that antibodies against human HSP60 is a specific part of the aetiology, through cross-reaction to bacterial HSP60, cannot be supported by results from this study. We suggest that the association between elevated levels of antibodies against human HSP60 and disease may reflect a general activation of the immune system and an increased expression of human HSP60 in the synovium of patients with SpA.</p></div

Evaluation of Bayesian Linear Regression Models as a Fine Mapping tool

Bayesian linear regression (BLR) models consider the underlying genetic architecture of complex phenotypes by specifying different prior distributions for SNP effects allowing heterogenous distribution of the true genetic signals. Our goal is to evaluate BLR models with BayesC and BayesR prior distributions for fine mapping on simulated and real binary and quantitative phenotypes, and compare them to the state-of-the-art external models: FINEMAP, SuSIE-RSS, SuSIE-Inf and FINEMAP-Inf. Evaluation of models was based on the F1 classification score for simulations, and predictive accuracy for the UK Biobank (UKB) phenotypes. We used over 533K genotyped SNPs (simulations) and 6.6 million imputed SNPs (UKB phenotypes), from over 335K White British Unrelated samples in the UK biobank. We simulated phenotypes from low (GA1) to moderate (GA2) polygenicity, heritability(h2) of 30% and 10%, causal SNPs (π) of 0.1% and 1% sampled genome-wide, and prevalence (PV) of 5% and 15%. Summary statistics and in-sample linkage disequilibrium were used to fit models in regions defined by lead SNPs. BayesR improved the F1 score, averaged across all simulations, by by 27.26%, 26.96%, 18.40%, 15.42%, and 13.32% relative to FINEMAP-Inf, BayesC, FINEMAP, SUSIE-RSS and SUSIE-Inf. Prediction R2, averaged across all the UKB quantitative phenotypes, with BayesR decreased by 5.32% and 3.71% compared to SuSIE-Inf and FINEMAP-Inf, whereas increased by 7.93% and 8.3% compared to SuSIE-RSS and BayesC. Prediction AUC, averaged across all the UKB binary phenotypes, with BayesR increased by 0.40%, 0.16%, 0.08%., and 0.05% relative to SuSIE-RSS, BayesC, FINEMAP-Inf, and SuSIE-Inf. These findings suggest that the performance of the BLR models was comparable to the state-of-the-art external models. The performance of BayesR prior was closely aligned with SuSIE-Inf and FINEMAP-Inf models. Results from both simulations and application of the models in the UKB phenotypes suggest that the BLR models are efficient fine mapping tools.<br/

IgG subclass antibodies to human and bacterial HSP60 are not associated with disease activity and progression over time in axial spondyloarthritis

INTRODUCTION: Spondyloarthritis (SpA), an interrelated group of rheumatic diseases, has been suggested to be triggered by bacterial infections prior to the development of an autoimmune response that causes inflammation of the spinal and peripheral joints. Because human heat shock protein 60 (HSP60), recently renamed HSPD1, and bacterial HSP60 are highly homologous, immunological cross-reactivity has been proposed as a mechanism of disease initiation. However, previous investigations of the humoral immune response to HSP60 in SpA patients have lacked determination of immunoglobulin G (IgG) subclasses and patient follow-up. In this study, we have focused on these parameters in a cohort of axial SpA patients with a well-established set of clinical characteristics, including MRI changes and human leukocyte antigen B27. METHODS: IgG subclass antibodies (IgG1, IgG2, IgG3 and IgG4) against recombinant HSP60 of three reactive arthritis-related bacteria; human HSP60; and the microorganisms Chlamydia trachomatis and C. pneumoniae were determined by ELISA. Serum samples collected from 2004 to 2006 and in 2010 and 2011 from 39 axial SpA patients were analyzed and compared with samples from 39 healthy controls. The Mann-Whitney U test and Wilcoxon matched pairs test were used to compare the antibody levels in different and paired groups, respectively. P < 0.01 was considered significant. The Spearman nonparametric correlation was used to determine correlation between antibody levels and between antibody levels and the disease parameters. RESULTS: Elevated levels of IgG1 and IgG3 to human HSP60 and IgG1 to HSP60 of Salmonella enterica Enteritidis were observed in SpA patients compared with healthy controls at both time points. The antibody levels were almost constant over time for IgG1, whereas high levels of IgG3 to human HSP60 tended to decrease over time. The antibody response to human HSP60 was predominantly of the IgG3 subclass, and patients with high levels of IgG3 to this antigen had low levels of IgG1, indicating an inverse association. Different IgG subclasses were produced against bacterial and human HSP60 in the same serum sample, IgG1 and IgG3, respectively, indicating that there was no cross-reaction. CONCLUSIONS: A significant association was observed between axial SpA and the presence of IgG1/IgG3 antibodies to human HSP60 and of IgG1 to S. enterica Enteritidis and C. trachomatis. Generation of antibodies to human HSP60 was independent of the presence of antibodies to bacterial HSP60. No association was observed between clinical and MRI changes with antibodies over time. Altogether, such antibodies do not reflect the disease activity in these patients. This study has been approved by the Regional Research Ethics Committee of Central Jutland, Denmark. Trial registration numbers: 20050046 and 2010008