Adipose tissue has recently been recognized as an important endocrine organ that plays a crucial role in energy metabolism and in the immune response in many metabolic tissues. With this regard, ...emerging evidence indicates that an important crosstalk exists between the adipose tissue and the brain. However, the contribution of adipose tissue to the development of age‐related diseases, including Alzheimer's disease, remains poorly defined. New studies suggest that the adipose tissue modulates brain function through a range of endogenous biologically active factors known as adipokines, which can cross the blood–brain barrier to reach the target areas in the brain or to regulate the function of the blood–brain barrier. In this review, we discuss the effects of several adipokines on the physiology of the blood–brain barrier, their contribution to the development of Alzheimer's disease and their therapeutic potential.
LINKED ARTICLES
This article is part of a themed issue From Alzheimer's Disease to Vascular Dementia: Different Roads Leading to Cognitive Decline. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v181.6/issuetoc
Although LC-MS untargeted metabolomics continues to expand into exiting research domains, methodological issues have not been solved yet by the definition of unbiased, standardized and globally ...accepted analytical protocols. In the present study, the response of the plasma metabolome coverage to specific methodological choices of the sample preparation (two SPE technologies, three sample-to-solvent dilution ratios) and the LC-ESI-MS data acquisition steps of the metabolomics workflow (four RP columns, four elution solvent combinations, two solvent quality grades, postcolumn modification of the mobile phase) was investigated in a pragmatic and decision tree-like performance evaluation strategy. Quality control samples, reference plasma and human plasma from a real nutrimetabolomic study were used for intermethod comparisons. Uni- and multivariate data analysis approaches were independently applied. The highest method performance was obtained by combining the plasma hybrid extraction with the highest solvent proportion during sample preparation, the use of a RP column compatible with 100% aqueous polar phase (Atlantis T3), and the ESI enhancement by using UHPLC-MS purity grade methanol as both organic phase and postcolumn modifier. Results led to the following considerations: submit plasma samples to hybrid extraction for removal of interfering components to minimize the major sample-dependent matrix effects; avoid solvent evaporation following sample extraction if loss in detection and peak shape distortion of early eluting metabolites are not noticed; opt for a RP column for superior retention of highly polar species when analysis fractionation is not feasible; use ultrahigh quality grade solvents and "vintage" analytical tricks such as postcolumn organic enrichment of the mobile phase to enhance ESI efficiency. The final proposed protocol offers an example of how novel and old-fashioned analytical solutions may fruitfully cohabit in untargeted metabolomics protocols.
Scope
The effects of triglyceride‐rich lipoproteins (TRLs) on the miRNA expression of endothelial cells, which are very involved in atherosclerosis, according to the type of diet are not known.
...Methods and Results
The differences between the effects of TRLs isolated from blood of subjects after a high‐fat meal with extra‐virgin olive oil (EVOO) and sunflower oil (SO) on the microRNA‐Seq profile related to atherosclerosis in human umbilical vein endothelial cells are analyzed. 28 upregulated microRNAs with EVOO‐derived TRLs, which can regulate 22 genes related to atherosclerosis, are found. 21 upregulated microRNAs with SO‐derived TRLs, which can regulate 20 genes related to atherosclerosis, are found. These microRNAs are mainly involved in angiogenesis, with a predominance of an anti‐angiogenic effect with EVOO‐derived TRLs. Other microRNAs upregulated with SO‐derived TRLs are involved in cardiovascular diseases. Pathways for the target genes obtained from the upregulated microRNA with EVOO‐derived TRLs are involved in lipid metabolism and inflammatory and defense response, while those with SO‐derived TRLs are involved in lipid metabolic process.
Conclusion
EVOO‐derived TRLs seem to produce a more atheroprotective profile than SO‐derived TRLs. This study provides alternative mechanisms on the protective role of EVOO against the atherogenic process through microRNA regulation in endothelial cells.
Triglyceride‐rich lipoproteins obtained after a high‐fat meal with extra‐virgin olive oil (EVOO) seem to produce a more atheroprotective miRNA profile than those obtained with sunflower oil (SO). Pathways for the target genes obtained from the upregulated miRNA with EVOO are involved in lipid metabolism and inflammatory and defense response, while those with SO are involved in lipid metabolic process.
(1) Background: There are conflicting results on whether weight loss after bariatric surgery (BS) might be associated with quality of life (QoL)/depressive symptomatology. We aim to determine whether ...BS outcomes are associated with QoL/depressive symptomatology in studied patients at the 8-year follow-up after BS, as well as their relationship with different serum proteins and miRNAs. (2) Methods: A total of 53 patients with class III obesity who underwent BS, and then classified into “good responders” and “non-responders” depending on the percentage of excess weight lost (%EWL) 8 years after BS (%EWL ≥ 50% and %EWL < 50%, respectively), were included. Basal serum miRNAs and different proteins were analysed, and patients completed tests to evaluate QoL/depressive symptomatology at 8 years after BS. (3) Results: The good responders group showed higher scores on SF-36 scales of physical functioning, role functioning—physical, role functioning—emotional, body pain and global general health compared with the non-responders. The expression of hsa-miR-101-3p, hsa-miR-15a-5p, hsa-miR-29c-3p, hsa-miR-144-3p and hsa-miR-19b-3p were lower in non-responders. Hsa-miR-19b-3p was the variable associated with the response to BS in a logistic regression model. (4) Conclusions: The mental health of patients after BS is limited by the success of the intervention. In addition, the expression of basal serum miRNAs related to depression/anxiety could predict the success of BS.
Abstract
Background
Recent reports have suggested that air pollution may impact thyroid function, although the evidence is still scarce and inconclusive. In this study we evaluated the association of ...exposure to air pollutants to thyroid function parameters in a nationwide sample representative of the adult population of Spain.
Methods
The Di@bet.es study is a national, cross-sectional, population-based survey which was conducted in 2008-2010 using a random cluster sampling of the Spanish population. The present analyses included 3859 individuals, without a previous thyroid disease diagnosis, and with negative thyroid peroxidase antibodies (TPO Abs) and thyroid-stimulating hormone (TSH) levels of 0.1-20 mIU/L. Participants were assigned air pollution concentrations for particulate matter <2.5μm (PM
2.5
) and Nitrogen Dioxide (NO
2
), corresponding to the health examination year, obtained by means of modeling combined with measurements taken at air quality stations (CHIMERE chemistry-transport model). TSH, free thyroxine (FT4), free triiodothyronine (FT3) and TPO Abs concentrations were analyzed using an electrochemiluminescence immunoassay (Modular Analytics E170 Roche).
Results
In multivariate linear regression models, there was a highly significant negative correlation between PM
2.5
concentrations and both FT4 (p<0.001), and FT3 levels (
p
<0.001). In multivariate logistic regression, there was a significant association between PM
2.5
concentrations and the odds of presenting high TSH OR 1.24 (1.01-1.52)
p
=0.043, lower FT4 OR 1.25 (1.02-1.54)
p
=0.032 and low FT3 levels 1.48 (1.19-1.84)
p
=<0.001 per each IQR increase in PM
2.5
(4.86 μg/m
3
). There was no association between NO
2
concentrations and thyroid hormone levels. No significant heterogeneity was seen in the results between groups of men, pre-menopausal and post-menopausal women.
Conclusions
Exposures to PM
2.5
in the general population were associated with mild alterations in thyroid function.
SCOPE: The effects that fatty acids (FAs) exert on G protein‐coupled receptor‐120 (GPR120) levels, a receptor for FAs, are still unknown. We analyzed the association between GPR120 and obesity, and ...the FA effects on its expression. METHODS AND RESULTS: GPR120 levels were analyzed in visceral adipose tissue (VAT) from nonobese and morbidly obese subject. VAT GPR120 mRNA and protein levels were lower in morbidly obese subjects (p = 0.004). After, these subjects underwent a high‐fat meal. GPR120 mRNA expression in peripheral blood mononuclear cells in the fasting state was lower in morbidly obese subjects (p = 0.04), with a decrease 3 h after a high‐fat meal only in morbidly obese subjects (p = 0.043). Also, incubations of visceral adipocytes from these subjects were made with different FAs. In nonobese subjects, palmitic, oleic, linoleic, and docosahexaenoic acids produced an increase in GPR120 mRNA and protein levels (p < 0.05). In morbidly obese subjects, only linoleic acid produced an increase in GPR120 mRNA and protein levels (p < 0.05). CONCLUSION: Morbidly obese subjects had lower GPR120 mRNA and protein levels in VAT and a lower mRNA expression after a high‐fat meal in peripheral blood mononuclear cells. The FAs effect on GPR120 mRNA and protein levels in visceral adipocytes was lower in morbidly obese subjects.
Aims
The paraoxonase‐1 (PON1) enzyme could play an important role in the anti‐oxidant capacity of high‐density lipoprotein. However, there are no studies which analyse the evolution of the three ...activities of PON1 (PON arylesterase, PON paraoxonase and PON lactonase) after Roux‐en‐Y Gastric Bypass (RYGB) in morbidly obese subjects. We analysed the association of PON concentration and activities with the evolution of morbidly obese subjects who underwent RYGB, and its relationship with biochemical variables and different atherogenic indices.
Methods
Twenty‐seven non‐obese and 82 morbidly obese subjects were studied before and 6 months after RYGB.
Results
Before RYGB, morbidly obese subjects had a lower PON1 concentration (P < 0.05) and higher PON lactonase activity (P < 0.001) than non‐obese subjects, with no differences in PON arylesterase and PON paraoxonase activities. After RYGB, PON1 concentration (P < 0.05) and PON lactonase activity (P < 0.001) decreased with regard to the presurgery state. PON lactonase activity correlated with the atherogenic index of plasma before (r = 0.19, P = 0.047) and after RYGB (r = 0.27, P = 0.035). In different multiple lineal regression analysis models, presurgery PON lactonase activity was associated with total cholesterol (β = 0.909, P < 0.001), LDL (β = 0.632, P = 0.006) and DBP (β = 0.230, P = 0.030) (R2 = 0.295), postsurgery PON lactonase activity was associated with esterified cholesterol (β = 0.362, P = 0.011) (R2 = 0.131), and the change (Δ) in PON lactonase activity after RYGB was associated with Δesterified cholesterol (β = 0.304, P = 0.030) (R2 = 0.093).
Conclusions
PON lactonase activity is associated with the presence of morbid obesity and with an impaired lipid profile. All associations found could indicate the relationship between PON lactonase activity and the development of atherosclerosis.
Oesophageal Squamous Cell Carcinoma (ESCC) is one of the two main subtypes of oesophageal cancer, affecting mainly populations in Asia. Though there have been great efforts to develop methods for a ...better prognosis, there is still a limitation in the staging of this affection. As a result, ESCC is detected at advances stages, when the interventions on the patient do not have such a positive outcome, leading in many cases to recurrence and to a very low 5-year survival rate, causing high mortality. A way to decrease the number of deaths is the use of biomarkers that can trace the advance of the disease at early stages, when surgical or chemotherapeutic methodologies would have a greater effect on the evolution of the subject. The new high throughput omics technologies offer an unprecedented chance to screen for thousands of molecules at the same time, from which a new set of biomarkers could be developed. One of the most convenient types of samples is saliva, an accessible body fluid that has the advantage of being non-invasive for the patient, being easy to store or to process. This review will focus on the current status of the new omics technologies regarding salivaomics in ESCC, or when not evaluated yet, the achievements in related diseases.
Alterations in intestinal microbiota composition could promote a proinflammatory state in adipose tissue that is associated with obesity and insulin resistance. Our aim was to identify the gut ...microbiota associated with insulin resistance in appendix samples from morbidly obese patients classified in 2 groups, high (IR-MO) and low insulin-resistant (NIR-MO), and to determine the possible association between these gut microbiota and variables associated with insulin resistance and the expression of genes related to inflammation and macrophage infiltration in adipose tissue. Appendix samples were obtained during gastric bypass surgery and the microbiome composition was determined by 16S rRNA pyrosequencing and bioinformatics analysis by QIIME. The Chao and Shannon indices for each study group suggested similar bacterial richness and diversity in the appendix samples between both study groups. 16S rRNA pyrosequencing showed that the IR-MO group had a significant increase in the abundance of
,
,
,
,
,
,
,
,
and
compared to the NIR-MO group. Moreover, in the IR-MO group we found a significant positive correlation between the abundance of
,
,
and
and the visceral adipose tissue expression level of IL6, TNF alpha, ILB1 and CD11b respectively, and significant negative correlations between the abundance of
and
, and plasma glucose and insulin levels, respectively. In conclusion, an appendix dysbiosis occurs in IR-MO patients, with a loss of butyrate-producing bacteria, essential to maintenance of gut integrity, together with an increase in mucin-degrading bacteria and opportunistic pathogens. The microbiota present in the IR-MO group were related to low grade inflammation in adipose tissue and could be useful for developing strategies to control the development of insulin resistance.
Obesity and obesity-related metabolic diseases are characterized by gut microbiota and epigenetic alterations. Recent insight has suggested the existence of a crosstalk between the gut microbiome and ...the epigenome. However, the possible link between alterations in gut microbiome composition and epigenetic marks in obesity has been not explored yet. The aim of this work is to establish a link between the gut microbiota and the global DNA methylation profile in a group of obese subjects and to report potential candidate genes that could be epigenetically regulated by gut microbiota in adipose tissue.
Gut microbiota composition was analyzed in DNA stool samples from 45 obese subjects by 16S ribosomal RNA (rRNA) gene sequencing. Twenty patients were selected based on their Bacteroidetes-to-Firmicutes ratio (BFR): HighBFR group (BFR > 2.5,
= 10) and LowBFR group (BFR < 1.2,
= 10). Genome-wide analysis of DNA methylation pattern in both whole blood and visceral adipose tissue of these selected patients was performed with an Infinium EPIC BeadChip array-based platform. Gene expression analysis of candidate genes was done in adipose tissue by real-time quantitative PCR.
Genome-wide analysis of DNA methylation revealed a completely different DNA methylome pattern in both blood and adipose tissue in the low BFR group vs. the high BFR group. Two hundred fifty-eight genes were differentially methylated in both blood and adipose tissue, of which several potential candidates were selected for gene expression analysis. We found that in adipose tissue, both
and
were hypomethylated and overexpressed in the low BFR group compared with the high BFR group. β values of both genes significantly correlated with the BFR ratio and the relative abundance of Bacteroidetes and/or Firmicutes.
In this study, we demonstrate that the DNA methylation status is associated with gut microbiota composition in obese subjects and that the expression levels of candidate genes implicated in glucose and energy homeostasis (e.g.,
and
) could be epigenetically regulated by gut bacterial populations in adipose tissue.
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