Methodological utility of chemerin as a novel biomarker of immunity and metabolism

Chemerin is a recently discovered adipokine with inflammatory and metabolic actions relevant for chronic disease development. However, evidence from human research on the role of chemerin in chronic disease risk is still lacking. We assessed the reliability of plasma chemerin concentrations measured on two occasions over a 4-month period in 207 apparently healthy participants. In addition, we explored the cross-sectional associations between chemerin and inflammatory biomarkers using Spearman partial correlation and multivariable linear regression analyses. Intra-individual reproducibility of chemerin measurements was assessed by calculating intraclass correlation coefficients (ICCs) and exploration of Bland–Altman plots. Reliability analyses revealed good reproducibility of chemerin measurements (ICC: 0.72 (95%-CI 0.65, 0.78)). Visual inspection of Bland–Altman plots confirmed that the two time point measurements had a high level of agreement. In correlation analyses, chemerin was positively correlated with adiposity measures (body mass index and waist circumference). In addition, independent of adiposity measures, chemerin was correlated with the biomarkers C-reactive protein, fatty acid-binding protein 4 and progranulin (Rho-s ranging from 0.23 to 0.37). In multivariable linear regression analysis, a combination of correlated factors including body mass index, waist circumference, C-reactive protein, progranulin and fatty acid- binding protein-4 explained 28.0% of chemerin concentrations. These findings demonstrate methodological utility of chemerin concentrations in population- based research setting. Human studies are highly warranted in order to provide further insights into the role of chemerin as a biomarker linking immunity and metabolism in relation to chronic disease risk

results of a randomized controlled trial

Bile acids (BAs) are increasingly recognised as metabolic regulators, potentially improving insulin sensitivity following bariatric surgery. However, physiological relevance of such observations remains unknown. Hence, we analysed serum BA composition and associated gut-derived hormone levels following lifestyle-induced weight loss in individuals with metabolic syndrome (MetS). 74 non-smoking men (45–55 yr) with MetS were randomised to a lifestyle-induced weight loss program (supervision via telemonitoring) or to a control arm. Before and after a 6 months intervention period clinical and laboratory parameters, body composition, serum BA profile, FGF-19, and GLP-1 concentrations were determined in fasting blood samples. 30 participants in the control and 33 participants in the treatment arm completed the study and were included in the data analysis. In participants of the treatment arm lifestyle-induced weight loss resulted in markedly improved insulin sensitivity. Serum levels of BA species and total GLP-1 decreased, while FGF-19 remained stable. Serum BA composition changed towards an increased 12α- hydroxylated/non-12α-hydroxylated ratio. None of these parameters changed in participants of the control arm. Our results demonstrate that improved metabolic control by lifestyle modifications lowers serum levels of BAs and GLP-1 and changes serum BA composition towards an increased 12α/non-12α ratio (ICTRP Trial Number: U1111-1158-3672)

Einfluss endokrin aktiver Nahrungsmittelkontaminanten auf die Entstehung von Fettzellen

Herkömmliche Erklärungsmodelle wie genetische Veränderungen, Ernährungs- und „Lifestyle“-Faktoren reichen nicht aus, um den weltweiten Anstieg der Adipositas, insbesondere bei Kindern und Jugendlichen, zu erklären. Hormonell wirksame Substanzen (EDC), wie Bisphenol A (BPA), Diethylhexylphthalat (DEHP) und Tributylzinn (TBT) werden hauptsächlich über die Nahrung aufgenommen und stehen im Verdacht, Entwicklungsprozesse zu stören. Die Ergebnisse dieser Arbeit belegen im in vitro Differenzierungsmodell von murinen mesenchymalen Stammzellen, dass Umwelthormone die Entstehung von Fettzellen PPARg-unabhängig, bereits während der frühen Determinierungsphase, und PPARg-abhängig während der späteren adipogenen Differenzierung, beeinflussen. Die ubiquitäre Exposition mit Umwelthormonen könnte die Entstehung von Adipositas und Übergewicht somit bereits während früher Phasen der Entwicklung fördern.Rising obesity rates (“obesity pandemics”) and related disorders belong to the most serious health challenges worldwide and it has been shown that pre- and postnatal genotype-environment interactions may contribute to the high prevalence of obesity. Endocrine disrupting compounds (EDC) like bisphenol A (BPA), bis(2-ethylhexyl)phthalate (DEHP) and tributyltin (TBT) are ubiquitously present in the environment and known to cross the placenta and to affect endocrine mediated pathways. This work shows that BPA, DEHP and TBT affect the adipogenic differentiation of murine embryonic stem cells in a concentration-, stage- and compound-specific manner. EDC affect adipogenesis by altering cell fate commitment of mesenchymal stem cells and by enhancing final adipogenic differentiation by different and independent mechanisms. Our results on the impact of EDC on early cell fate development in undifferentiated progenitors may document a novel mechanistic insight into predisposition for obesity.von Ronald Bieman

A Reliability Study in a Cohort of 207 Apparently Healthy Participants

The reliability of single time point measurements of the novel adipokines retinol-binding protein 4 and omentin-1 in the blood has not been evaluated in large samples yet. The present study aimed to assess the amount of biological variation of these two adipokines within individuals. The study sample comprised 207 participants (124 women and 83 men) from Potsdam (Germany) and surrounding areas, with an average age of 56.5 years (SD 4.2). Blood samples were collected from each participant twice, approximately four months apart. Using enzyme linked immunosorbent assays, the concentrations of retinol- binding protein 4 and omentin-1 were determined in EDTA plasma. As indicators of reliability, intraclass correlation coefficients (ICCs) were calculated from the repeated biomarker measurements. The ICCs for repeated retinol- binding protein 4 and omentin-1 measurements were 0.77 (95% CI 0.71, 0.82) and 0.83 (95% CI 0.78, 0.87), respectively, indicating for both adipokines excellent reliability. ICCs were stable across strata according to sex, age, BMI, and blood pressure. Thus, for epidemiological studies it seems reasonable to rely on concentrations of retinol-binding protein 4 and omentin-1 in samples from a single time point if repeated measurements are not available

The Influence of Steroid Hormones on Tooth Wear in Children and in Adolescents

(1) Background: From a young age, boys are more often affected by tooth wear than girls. This suggests an influence of the male sex hormone (testosterone) on the aetiology of tooth wear. The aim of the present study was to investigate the incidence of tooth wear in relation to steroid hormone levels in children. (2) Methods: 1022 test persons aged between 10 and 18 (491 male, 531 female) from the LIFE Child study underwent medical and dental examination. Tooth wear was measured through clinical inspection. Blood samples were taken to determine hormone levels (testosterone, SHBG). The level of free testosterone was calculated from the ratio of testosterone to SHBG. Using multivariable methods, the incidence of tooth wear was analyzed as a function of hormone levels, while controlling for confounders such as age, sex, social status, and orthodontic treatment. (3) Results: The incidence of tooth wear increased with age in both sexes. Boys showed significantly more often attrition facets than girls (17.5% vs. 13.2%, p < 0.001). Subjects with tooth wear showed significantly higher free testosterone levels than those without (males: p < 0.001, females: p < 0.05). After controlling for confounding variables, the risk of tooth wear increased by approximately 30.0% with each year of life (odds ratio [OR]boys = 1.29, 95% confidence interval [CI] = 1.04–1.56; [OR]girls = 1.32, 95% CI = 1.08–1.61). In addition, the risk of tooth wear increased by 6.0% per free testosterone scale score only in boys (OR = 1.06, 95% CI = 1.01–1.12). (4) Conclusions: Tooth wear is common in children and in adolescents, and it increases steadily with age in both sexes. The stronger increase and the higher prevalence among male adolescents can be explained by the additional effect of free testosterone

13-hydroxy linoleic acid increases expression of the cholesterol transporters ABCA1, ABCG1 and SR-BI and stimulates apoA-I-dependent cholesterol efflux in RAW264.7 macrophages

<p>Abstract</p> <p>Background</p> <p>Synthetic activators of peroxisome proliferator-activated receptors (PPARs) stimulate cholesterol removal from macrophages through PPAR-dependent up-regulation of liver × receptor α (LXRα) and subsequent induction of cholesterol exporters such as ATP-binding cassette transporter A1 (ABCA1) and scavenger receptor class B type 1 (SR-BI). The present study aimed to test the hypothesis that the hydroxylated derivative of linoleic acid (LA), 13-HODE, which is a natural PPAR agonist, has similar effects in RAW264.7 macrophages.</p> <p>Methods</p> <p>RAW264.7 macrophages were treated without (control) or with LA or 13-HODE in the presence and absence of PPARα or PPARγ antagonists and determined protein levels of LXRα, ABCA1, ABCG1, SR-BI, PPARα and PPARγ and apolipoprotein A-I mediated lipid efflux.</p> <p>Results</p> <p>Treatment of RAW264.7 cells with 13-HODE increased PPAR-transactivation activity and protein concentrations of LXRα, ABCA1, ABCG1 and SR-BI when compared to control treatment (P < 0.05). In addition, 13-HODE enhanced cholesterol concentration in the medium but decreased cellular cholesterol concentration during incubation of cells with the extracellular lipid acceptor apolipoprotein A-I (P < 0.05). Pre-treatment of cells with a selective PPARα or PPARγ antagonist completely abolished the effects of 13-HODE on cholesterol efflux and protein levels of genes investigated. In contrast to 13-HODE, LA had no effect on either of these parameters compared to control cells.</p> <p>Conclusion</p> <p>13-HODE induces cholesterol efflux from macrophages via the PPAR-LXRα-ABCA1/SR-BI-pathway.</p

A two-and-a-half-year-old breastfed toddler presenting with anemia: a case report

BACKGROUND: Anemia is a common presentation in children but the differential diagnosis of iron deficiency and β-thalassemia remains a diagnostic challenge. Red blood cell indices have been shown to perform weakly in such scenarios. One potential cause is breastfeeding, but the evidence for unusually prolonged exclusive breastfeeding as a cause of iron deficiency anemia in older (>2 years) toddlers is sparse and the association of breastfeeding with iron deficiency in this age group of older toddlers is not unequivocally established. In this case we describe an unusual cause of nutritional iron deficiency anemia in the age group of 2–3 years. CASE PRESENTATION: We describe a two-and-a-half-year-old Turkish boy who presented to our outpatient clinic with recurrent diarrhea and anemia. The patient was febrile (99.1°F) with pale skin and signs of mild dehydration. A reduced nutritional status with a weight of 11.5 kg between the 3rd and 10th percentile was noted. Nutritional evaluation revealed that the boy was still exclusively breastfed with more than 6 times breastfeedings per day. Iron supplementation ameliorated the anemia and reduced hypochromic red blood cells. CONCLUSION: The case demonstrates that unusually prolonged (longer than two years) exclusive breastfeeding is a potential cause of iron deficiency anemia in older toddlers. We discuss a simple combination of laboratory tests with ferritin and red cell distribution width that together with a nutritional evaluation provide a quick diagnosis and show that even at such an advanced stage of nutritional iron deficiency oral iron supplementation is an effective treatment

Transcriptome Analyses of Adipose Tissue Samples Identify EGFL6 as a Candidate Gene Involved in Obesity-Related Adipose Tissue Dysfunction in Children

Obesity develops early in childhood and is accompanied by early signs of adipose tissue (AT) dysfunction and metabolic disease in children. In order to analyse the molecular processes during obesity-related AT accumulation in children, we investigated genome-wide expression profiles in AT samples, isolated adipocytes, and stromal vascular fraction (SVF) cells and assessed their relation to obesity as well as biological and functional AT parameters. We detected alterations in gene expression associated with obesity and related parameters, i.e., BMI SDS, adipocyte size, macrophage infiltration, adiponectin, and/or leptin. While differential gene expression in AT and adipocytes shared an enrichment in metabolic pathways and pathways related to extracellular structural organisation, SVF cells showed an overrepresentation in inflammatory pathways. In adipocytes, we found the strongest positive association for epidermal growth factor-like protein 6 (EGFL6) with adipocyte hypertrophy. EGFL6 was also upregulated during in vitro adipocyte differentiation. In children, EGFL6 expression was positively correlated to parameters of AT dysfunction and metabolic disease such as macrophage infiltration into AT, hs-CRP, leptin levels, and HOMA-IR. In conclusion, we provide evidence for early alterations in AT gene expression related to AT dysfunction in children and identified EGFL6 as potentially being involved in processes underlying the pathogenesis of metabolic disease

Osteocalcin Is Independently Associated with C-Reactive Protein during Lifestyle-Induced Weight Loss in Metabolic Syndrome

Bone-derived osteocalcin has been suggested to be a metabolic regulator. To scrutinize the relation between osteocalcin and peripheral insulin sensitivity, we analyzed changes in serum osteocalcin relative to changes in insulin sensitivity, low-grade inflammation, and bone mineral density following lifestyle-induced weight loss in individuals with metabolic syndrome (MetS). Participants with MetS were randomized to a weight loss program or to a control group. Before and after the 6-month intervention period, clinical and laboratory parameters and serum osteocalcin levels were determined. Changes in body composition were analyzed by dual-energy X-ray absorptiometry (DXA). In participants of the intervention group, weight loss resulted in improved insulin sensitivity and amelioration of inflammation. Increased serum levels of osteocalcin correlated inversely with BMI (r = −0.63; p < 0.001), total fat mass (r = −0.58, p < 0.001), total lean mass (r = −0.45, p < 0.001), C-reactive protein (CRP) (r = −0.37; p < 0.01), insulin (r = −0.4; p < 0.001), leptin (r = −0.53; p < 0.001), triglycerides (r = −0.42; p < 0.001), and alanine aminotransferase (ALAT) (r = −0.52; p < 0.001). Regression analysis revealed that osteocalcin was independently associated with changes in CRP but not with changes in insulin concentration, fat mass, or bone mineral density, suggesting that weight loss-induced higher serum osteocalcin is primarily associated with reduced inflammation

Gene expression profile of CD14+ blood monocytes following lifestyle-induced weight loss in individuals with metabolic syndrome.

Lifestyle-induced weight loss is regarded as an efficient therapy to reverse metabolic syndrome (MetS) and to prevent disease progression. The objective of this study was to investigate whether lifestyle-induced weight loss modulates gene expression in circulating monocytes. We analyzed and compared gene expression in monocytes (CD14+ cells) and subcutaneous adipose tissue biopsies by unbiased mRNA profiling. Samples were obtained before and after diet-induced weight loss in well-defined male individuals in a prospective controlled clinical trial (ICTRP Trial Number: U1111-1158-3672). The BMI declined significantly (- 12.6%) in the treatment arm (N = 39) during the 6-month weight loss intervention. This was associated with a significant reduction in hsCRP (- 45.84%) and circulating CD14+ cells (- 21.0%). Four genes were differentially expressed (DEG's) in CD14+ cells following weight loss (ZRANB1, RNF25, RB1CC1 and KMT2C). Comparative analyses of paired CD14+ monocytes and subcutaneous adipose tissue samples before and after weight loss did not identify common genes differentially regulated in both sample types. Lifestyle-induced weight loss is associated with specific changes in gene expression in circulating CD14+ monocytes, which may affect ubiquitination, histone methylation and autophag