Scope
Our aim was to investigate whether the inflammatory state associated to metabolic syndrome (MetS) patients is affected by diets with different fat quality and quantity.
Methods and results
...Seventy‐five subjects from LIPGENE cohort were included in this feeding trial and randomly assigned to one of four diets: high saturated fatty acids (HSFA); high monounsaturated fatty acids (HMUFA) and two low‐fat, high complex carbohydrate (LFHCC) diets, supplemented with long‐chain n‐3 polyunsaturated fatty acids (LFHCC n‐3) or placebo (LFHCC), for 12 weeks each. A postprandial fat challenge, reflecting the intervention dietary fat composition, was conducted post‐intervention. The HMUFA diet significantly reduced postprandial nuclear transcription factor‐kappaB (NF‐kB) activity and the nuclear p65 protein levels relative to fasting values (p < 0.05). Furthermore, we observed a postprandial decrease in this protein with the HMUFA diet compared with the HSFA and LFHCC diets (p < 0.05). The postprandial response of inhibitory molecule from NF‐kB mRNA levels increased with the HMUFA diet compared with the HSFA and LFHCC n‐3 diets (p < 0.05). Postprandial tumor necrosis factor‐α and Metalloproteinase 9 mRNA levels were also reduced after the HMUFA diet compared with the HSFA diet (p < 0.05).
Conclusion
Our results indicate that the long‐term consumption of a healthy diet model with HMUFA attenuates the postprandial inflammatory state associated with MetS.
Genotypic and phenotypic data of 1,562 animals were analyzed to find genomic regions that potentially influence the birth weight (BW), weaning weight at seven months of age (WW) and yearling weight ...(YW) of Colombian Brahman cattle, with genotyping conducted using Illumina Bead chip array with 74,669 SNPs. A Single Step Genomic BLUP (ssGBLP), approach was used to estimate the proportion of variance explained by each marker. Multiple regions scattered across the genome were found to influence weights at different ages, also dependent on the trait component (direct or maternal). The most interesting regions were connected to previously identified QTLs and genes, such as ADAMTSL3, CAPN2, CAPN2, FABP6, ZEB2 influencing growth and weight traits. The identified regions will contribute to the development and refinement of genomic selection programs for Zebu Brahman cattle in Colombia.
Adipocyte dysfunction in obesity is commonly associated with impaired insulin signalling in adipocytes and insulin resistance. Insulin signalling has been associated with caveolae, which are coated ...by large complexes of caveolin and cavin proteins, along with proteins with membrane‐binding and remodelling properties. Here, we analysed the regulation and function of a component of caveolae involved in growth factor signalling in neuroendocrine cells, neuroendocrine long coiled‐coil protein‐2 (NECC2), in adipocytes. Studies in 3T3‐L1 cells showed that NECC2 expression increased during adipogenesis. Furthermore, NECC2 co‐immunoprecipitated with caveolin‐1 (CAV1) and exhibited a distribution pattern similar to that of the components of adipocyte caveolae, CAV1, Cavin1, the insulin receptor and cortical actin. Interestingly, NECC2 overexpression enhanced insulin‐activated Akt phosphorylation, whereas NECC2 downregulation impaired insulin‐induced phosphorylation of Akt and ERK2. Finally, an up‐regulation of NECC2 in subcutaneous and omental adipose tissue was found in association with human obesity and insulin resistance. This effect was also observed in 3T3‐L1 adipocytes exposed to hyperglycaemia/hyperinsulinemia. Overall, the present study identifies NECC2 as a component of adipocyte caveolae that is regulated in response to obesity and associated metabolic complications, and supports the contribution of this protein as a molecular scaffold modulating insulin signal transduction at these membrane microdomains.
The food industry faces significant challenges in generating biodegradable materials for packaging food. Studies on the production of edible films and coatings based on macromolecules such as ...carbohydrates, proteins, and lipids (and their combination) from cereal grains or legumes have provided helpful information about component concentrations, interactions, and the optimal conditions to elaborate films or coatings. However, the final application of edible films and coatings can depend on the compatibility between polymer matrix materials and their mechanical and barrier properties. This paper reviews the utilization of proteins from cereal and legumes in the development of edible films and the processing conditions that potentially modify the functional properties of the films, including the combination with additives to improve their properties enhancing food handling, transportation, storage, and preservation, without affecting the environment. In addition, the present research addresses the main methods to elaborate edible films and the use of novel technologies in film formulation.
Abstract
Adipocyte dysfunction in obesity is commonly associated with impaired insulin signalling in adipocytes and insulin resistance. Insulin signalling has been associated with caveolae, which are ...coated by large complexes of caveolin and cavin proteins, along with proteins with membrane‐binding and remodelling properties. Here, we analysed the regulation and function of a component of caveolae involved in growth factor signalling in neuroendocrine cells, neuroendocrine long coiled‐coil protein‐2 (
NECC
2), in adipocytes. Studies in 3T3‐L1 cells showed that
NECC
2 expression increased during adipogenesis. Furthermore,
NECC
2 co‐immunoprecipitated with caveolin‐1 (
CAV
1) and exhibited a distribution pattern similar to that of the components of adipocyte caveolae,
CAV
1, Cavin1, the insulin receptor and cortical actin. Interestingly,
NECC
2 overexpression enhanced insulin‐activated Akt phosphorylation, whereas
NECC
2 downregulation impaired insulin‐induced phosphorylation of Akt and
ERK
2. Finally, an up‐regulation of
NECC
2
in subcutaneous and omental adipose tissue was found in association with human obesity and insulin resistance. This effect was also observed in 3T3‐L1 adipocytes exposed to hyperglycaemia/hyperinsulinemia. Overall, the present study identifies
NECC
2 as a component of adipocyte caveolae that is regulated in response to obesity and associated metabolic complications, and supports the contribution of this protein as a molecular scaffold modulating insulin signal transduction at these membrane microdomains.
Lipid droplets (LDs) are organelles that coordinate lipid storage and mobilization, both processes being especially important in cells specialized in managing fat, the adipocytes. Proteomic analyses ...of LDs have consistently identified the small GTPase Rab18 as a component of the LD coat. However, the specific contribution of Rab18 to adipocyte function remains to be elucidated. Herein, we have analyzed Rab18 expression, intracellular localization and function in relation to the metabolic status of adipocytes. We show that Rab18 production increases during adipogenic differentiation of 3T3-L1 cells. In addition, our data show that insulin induces, via phosphatidylinositol 3-kinase (PI3K), the recruitment of Rab18 to the surface of LDs. Furthermore, Rab18 overexpression increased basal lipogenesis and Rab18 silencing impaired the lipogenic response to insulin, thereby suggesting that this GTPase promotes fat accumulation in adipocytes. On the other hand, studies of the β-adrenergic receptor agonist isoproterenol confirmed and extended previous evidence for the participation of Rab18 in lipolysis. Together, our data support the view that Rab18 is a common mediator of lipolysis and lipogenesis and suggests that the endoplasmic reticulum (ER) is the link that enables Rab18 action on these two processes. Finally, we describe, for the first time, the presence of Rab18 in human adipose tissue, wherein the expression of this GTPase exhibits sex- and depot-specific differences and is correlated to obesity. Taken together, these findings indicate that Rab18 is involved in insulin-mediated lipogenesis, as well as in β-adrenergic-induced lipolysis, likely facilitating interaction of LDs with ER membranes and the exchange of lipids between these compartments. A role for Rab18 in the regulation of adipocyte biology under both normal and pathological conditions is proposed.
We aimed to identify the plasma miRNA profile of antiphospholipid syndrome (APS) patients and to investigate the potential role of specific circulating miRNAs as non-invasive disease biomarkers. ...Ninety APS patients and 42 healthy donors were recruited. Profiling of miRNAs by PCR-array in plasma of APS patients identified a set of miRNAs differentially expressed and collectively involved in clinical features. Logistic regression and ROC analysis identified a signature of 10 miRNA ratios as biomarkers of disease. In addition, miRNA signature was related to fetal loss, atherosclerosis, and type of thrombosis, and correlated with parameters linked to inflammation, thrombosis, and autoimmunity. Hard clustering analysis differentiated 3 clusters representing different thrombotic risk profile groups. Significant differences between groups for several miRNA ratios were found. Moreover, miRNA signature remained stable over time, demonstrated by their analysis three months after the first sample collection. Parallel analysis in two additional cohorts of patients, including thrombosis without autoimmune disease, and systemic lupus erythematosus without antiphospholipid antibodies, each displayed specific miRNA profiles that were distinct from those of APS patients.
, antiphospholipid antibodies of IgG isotype promoted deregulation in selected miRNAs and their potential atherothrombotic protein targets in monocytes and endothelial cells. Taken together, differentially expressed circulating miRNAs in APS patients, modulated at least partially by antiphospholipid antibodies of IgG isotype, might have the potential to serve as novel biomarkers of disease features and to typify patients' atherothrombotic status, thus constituting a useful tool in the management of the disease.
The advent of anti-tumor necrosis factor alpha (anti-TNFα) drugs has considerably improved medical management in rheumatoid arthritis (RA) patients, although it has been reported to be ineffective in ...a fraction of them. MicroRNAs (miRNAs) are small, non-coding RNAs that act as fine-tuning regulators of gene expression. Targeting miRNAs by gain or loss of function approaches have brought therapeutic effects in various disease models. The aim of this study was to investigate serum miRNA levels as predictive biomarkers of response to anti-TNFα therapy in RA patients.
In total, 95 RA patients undergoing anti-TNFα/disease-modifying antirheumatic drugs (anti-TNFα/DMARDs) combined treatments were enrolled. Serum samples were obtained at 0 and 6 months and therapeutic efficacy was assessed. miRNAs were isolated from the serum of 10 patients before and after anti-TNFα/DMARDs combination therapy, cDNA transcribed and pooled, and human serum miRNA polymerase chain reaction (PCR) arrays were performed. Subsequently, selected miRNAs were analyzed in a validation cohort consisting of 85 RA patients. Correlation studies with clinical and serological variables were also performed.
Ninety percent of RA patients responded to anti-TNFα/DMARDs combination therapy according to European League Against Rheumatism (EULAR) criteria. Array analysis showed that 91% of miRNAS were overexpressed and 9% downregulated after therapy. Functional classification revealed a preponderance of target mRNAs involved in reduction of cells maturation--especially on chondrocytes--as well as in immune and inflammatory response, cardiovascular disease, connective tissue and musculoskeletal system. Six out of ten miRNAs selected for validation were found significantly upregulated by anti-TNFα/DMARDs combination therapy (miR-16-5p, miR-23-3p, miR125b-5p, miR-126-3p, miRN-146a-5p, miR-223-3p). Only responder patients showed an increase in those miRNAs after therapy, and paralleled the reduction of TNFα, interleukin (IL)-6, IL-17, rheumatoid factor (RF), and C-reactive protein (CRP). Correlation studies demonstrated associations between validated miRNAs and clinical and inflammatory parameters. Further, we identified a specific plasma miRNA signature (miR-23 and miR-223) that may serve both as predictor and biomarker of response to anti-TNFα/DMARDs combination therapy.
miRNA levels in the serum of RA patients before and after anti-TNFα/DMARDs combination therapy are potential novel biomarkers for predicting and monitoring therapy outcome.
To evaluate long-term visual and anatomical outcomes in neovascular age-related macular degeneration (nAMD) patients treated with anti-vascular endothelial growth factor (VEGF) agents depending on ...the time delay from confirmed diagnosis to treatment initiation.
Seventy-three nAMD patients (73 eyes) treated with anti-VEGF agents for 12 months using the pro re nata regimen were included in this retrospective longitudinal study. Patients were split into 3 groups according to the time from diagnosis to first anti-VEGF injection: < 48 h (group 1); 48 h-7 days (group 2); > 7 days (group 3). Decimal best-corrected visual acuity (VA) and macular thickness (MT) were recorded at baseline and 1–2-, 3–4-, 6- and 12-month later. Furthermore, age, gender as well as the applied treatment and number of injections after 12 months of treatment were also registered and compared.
Long-term effect of the treatment demonstrated enhanced VA in group 1 patients compared with the rest of groups after 1–2-, 6-, and 12-month follow-up (P < 0.05). Positive effects of early treatment were additionally corroborated by the augmented percentage of patients with normal VA in the group 1 respect to the rest of groups over studied time points (P < 0.05). Moreover, the VA gain in nAMD at group 1 was obtained with a mean of 3.7 intravitreal injections over 1-year follow-up period. Regarding MT, non-significant difference was observed among groups.
An early initial treatment with VEGF inhibitors is critical to achieve the best functional benefits of this therapy in new-onset nAMD patients.
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•Anti-VEGF therapy within 48 h from diagnosis leads to long-term visual gain in nAMD.•Visual gain is achieved with low IV injection number if early treatment is applied.•A prompt first anti-VEGF injection promotes long-term anatomical benefits in nAMD.