Lipogenic activity in goats (Blanca celtibérica) with different body condition scores

The aim was to study the variation in the amount of adipose tissue, size and number of adipocytes and lipogenic enzyme activities in does with different body condition scores (BCS). These parameters were studied in the omental (OM), mesenteric (MES), perirenal (PR), subcutaneous (SC) and intermuscular (IM) fat depots of 22 adult, non-pregnant and non-lactating Blanca celtibérica does, with a BCS ranging from 1.5 to 4.5 (scale 0–5). SC adipose tissue showed the highest deposition-mobilization phase (highest fat relative to the variation per BCS unit of 74%), followed by OM (65%), PR (63%), MES (48%) and IM (46%) adipose depots. Adipocyte size varied with the amount of fat (P < 0.001), while the SC depot was the only depot that showed a positive correlation between adipocyte number and BCS (r² = 0.20; P < 0.05). The activities of glycerol 3-phosphate dehydrogenase (G3PDH) and fatty acid synthetase (FAS) enzymes were not generally affected by BCS, due to the fact that animals were on a maintenance diet prior to slaughter. The findings obtained in this work indicate that the processes of storage and mobilization of fat reserves in adult goats are principally due to variation in the size of the adipocyte cells. Therefore, the use of BCS could be a good method for predicting nutritional status in goats.     

MicroRNA-224 upregulation and AKT activation synergistically predict poor prognosis in patients with hepatocellular carcinoma

Background and aimPrevious evidence has shown that microRNA (miR)-224 may function as an onco-miRNA in hepatocellular carcinoma (HCC) cells by activating AKT signaling. However, little is known about the clinical significance of the combined expression of miR-224 and phosphorylated-AKT (pAKT) on human HCC. The aim of this study was to investigate the synergistical influence of miR-224 and pAKT on clinical characteristics and prognosis in patients with HCC.MethodsOne-hundred and thirty HCC patients who had undergone curative liver resection were selected. In situ hybridization and immunohistochemistry were respectively performed to detect the expression of miR-224 and pAKT in the respective tumors.ResultsCompared with the adjacent nonneoplastic liver tissues, the expression levels of miR-224 and pAKT protein in HCC tissues were both significantly increased (both P < 0.001). In addition, the combined upregulation of miR-224 and pAKT protein was significantly associated with serum AFP (P = 0.01), tumor stage (P = 0.002) and tumor grade (P = 0.008). Moreover, HCC patients highly expressing both miR-224 and pAKT protein had worse 5-year disease-free survival and 5-year overall survival (both P < 0.001). Furthermore, the Cox proportional hazards model showed that the combined upregulation of miR-224 and pAKT protein (miR-224-high/pAKT-high) may be independent poor prognostic factors for both 5-year disease-free survival (P = 0.008) and 5-year overall survival (P = 0.01) in HCC.ConclusionThese results indicate for the first time that miR-224 upregulation and AKT activation may synergistically associate with tumor progression of HCC. The combined high expression of miR-224 and pAKT may be a potential indicator for predicting unfavorable prognosis in HCC patients.     

A let-7 microRNA polymorphism in the KRAS 3′-UTR is prognostic in oropharyngeal cancer

IntroductionThis study aimed to investigate the effect of genetic polymorphisms in miRNA sequences, miRNA target genes and miRNA processing genes as additional biomarkers to HPV for prognosis in oropharyngeal squamous cell carcinoma (OPSCC) patients. Secondarily, the prevalence of HPV-associated OPSCC in a European cohort was mapped.MethodsOPSCC patients (n = 122) were genotyped for ten genetic polymorphisms in pre-miRNAs (pre-mir-146a, pre-mir-196a2), in miRNA biosynthesis genes (Drosha, XPO5) and in miRNA target genes (KRAS, SMC1B). HPV status was assessed by p16 immunohistochemistry (IHC) and high-risk HPV in situ hybridization (ISH) or by p16 IHC and PCR followed by enzyme-immunoassay (EIA). Overall and disease specific survival were analysed using Kaplan–Meier plots (log-rank test). Cox proportional hazard model was used to calculate hazard ratios (HR).ResultsThe overall HPV prevalence rate in our Belgian/Dutch cohort was 27.9%. Patients with HPV⁺ tumours had a better 5-years overall survival (78% vs. 46%, p = 0.001) and a better 5-years disease specific survival (90% vs. 70%, p = 0.016) compared to patients with HPV⁻ tumours. In multivariate Cox analysis including clinical, treatment and genetic parameters, HPV negativity (HR = 3.89, p = 0.005), advanced T-stage (HR = 1.81, p = 0.050), advanced N-stage (HR = 5.86, p = 0.001) and >10 pack-years of smoking (HR = 3.45, p = 0.012) were significantly associated with reduced overall survival. The variant G-allele of the KRAS-LCS6 polymorphism was significantly associated with a better overall survival (HR = 0.40, p = 0.031).ConclusionsOur results demonstrate that OPSCC patients with the KRAS-LCS6 variant have a better outcome and suggest that this variant may be used as a prognostic biomarker for OPSCC.     

Effects of hydroxysafflor yellow A on ALDH1: Inhibition kinetics and molecular dynamics simulation

Hydroxysafflor yellow A (HSYA) is a potent natural antioxidant that displays important neuroprotective activity. Inhibition of acetaldehyde dehydrogenase 1 (ALDH1) has attracted the attention of researchers due to its overexpression in several types of cancers. We studied the effects of HSYA on ALDH1 by evaluating the inhibitory kinetics based on its antioxidant properties and performing computational simulation integrating methods. HSYA reversibly inhibited human recombinant ALDH1 via non-competitive inhibition (K_i = 0.267 ± 0.024 mM). We also investigated the tertiary structural changes via measuring intrinsic and ANS-binding fluorescence. The results indicated that the inactivation induced by HSYA was associated with structural changes. To obtain further information, we simulated the 3D structure of ALDH1 and conducted computational docking simulations as well as molecular dynamics simulations. The results indicated that 4 rings of HSYA interact with several residues near the ALDH1 active site. Our study provides insight into the inhibition of ALDH1 accompanied by structural changes. Based on its ALDH1-inhibiting effect and its potential as a natural antioxidant, HSYA is a potential agent for treating ALDH1-associated cancers.     

Fish-oil-derived n-3 polyunsaturated fatty acids reduce NLRP3 inflammasome activity and obesity-related inflammatory cross-talk between adipocytes and CD11b+ macrophages

Adipocyte–macrophage cross-talk propagates immune responses in obese adipose tissue (AT). Long-chain n-3 polyunsaturated fatty acids (LC n-3 PUFA) mitigate inflammation, partly through up-regulation of adiponectin; however, specific mechanisms are unclear. We determined if adipocyte–macrophage cross-talk could be mitigated by dietary LC n-3 PUFA and if this was dependent on adiponectin-mediated signaling. We utilized an in vitro co-culture model mimicking the ratio of adipocytes:macrophages in obese AT, whereby 3T3-L1 adipocytes were co-cultured with splenic CD11b⁺ macrophages from C57BL/6 mice fed high-fat control (HF-CON; 34% w/w fat) or fish oil diets (HF-FO; 34% w/w fat containing 7.6% w/w FO), as well as mice fed low-fat control (LF-CON; 10% w/w fat) or FO diets (LF-FO; 10% w/w fat containing 3% w/w FO). Co-culture conditions tested effects of soluble mediator-driven mechanisms (trans-well system), cell contact and low-dose lipopolysaccharide (LPS) mimicking acute or chronic inflammatory conditions. HF-FO macrophages from acute LPS-stimulated trans-well co-cultures had decreased mRNA expression of Casp1, Il1β and Il18, as well as cellular caspase-1 activity compared to HF-CON macrophages (P ≤ .05). Moreover, adipocytes from acute LPS-stimulated HF-FO co-cultures had decreased caspase-1 activity and decreased IL-1β/IL-18 levels following chronic LPS pretreatment compared to HF-CON co-cultures (P ≤ .05). Additionally, in contact co-cultures with adiponectin-neutralizing antibody, the FO-mediated modulation of NFκB activity and decrease in phosphorylated p65 NFκB, expression of NLRP3 inflammasome genes, M1 macrophage marker genes and inflammatory cytokine/chemokine secretion were controlled partly through adiponectin, while cellular caspase-1 activity and IL-1β/1L-18 levels were decreased independently of adiponectin (P ≤ .05). LC n-3 PUFA may decrease the intensity of adipocyte–macrophage cross-talk to mitigate obesity-associated pathologies.     

Association between selenium nutritional status and metabolic risk factors in men with visceral obesity

Background and aimPrevious evidence has suggested an association between selenium and cardiovascular disease, which is main outcome of metabolic syndrome. The aim of this study was to examine possible correlation between selenium nutritional status and metabolic risk factors in men with visceral obesity.MethodsPlasma samples were collected from 123 Indonesian men with visceral obesity. Their metabolic risk factors and selenium nutritional status were analyzed. The eligible subjects (n = 78) were stratified according to the International Diabetes Federation: obese, obese plus one component, and obese plus two components or more. Obese plus two components or more were diagnostic criteria of metabolic syndrome. Pearson's correlation was performed to examine the correlation in each group.ResultsIn the obese group, selenium positively correlated with high-density lipoprotein (HDL) cholesterol (r = 0.390, P < 0.05) and with fatty acid binding protein-4 (FABP4) (r = 0.474, P < 0.05); glutathione peroxidase-3 (GPx3) activity was inversely correlated with FABP4 (r = ?467, P < 0.05). In the obese plus one component group, GPx3 activity positively correlated with HDL cholesterol (r = 0.413, P < 0.05). In the metabolic syndrome group, selenium negatively correlated with monocytes chemoattractant protein (MCP)-1 (r = ?0.429, P < 0.05).ConclusionsThese results show that the association between selenium nutritional status and metabolic risk factors is limited to particular group of obese men with or without metabolic syndrome.     

Improving and evaluating the soil cover indicator for agricultural land in Canada

A soil cover days (SCD) model has been developed by Agriculture and Agri-Food Canada for use as an agri-environmental indicator to monitor the relationship between agricultural production activities and agri-environmental quality. The SCD indicator integrates information on crops, soils, climate, and field activities to estimate the total equivalent number of days that agricultural soils are covered by crop canopy, crop residue and snow in a given year. Daily cover fractions of plant and residue for a given crop in an ecoregion are simulated using typical crop calendar and field management practices, and the equivalent number of days that soil is covered by snow in winter is derived from long term climate normals. The equivalent SCD for a spatial unit is then derived as the area-weighted sum of different crops and different management practices within the unit. This paper presents the SCD framework, details an assessment of the accuracy of the model and outlines future improvements. Annual snow days derived from 30-year climate normals as used in the model was strongly correlated (excluding mountain areas) with that derived from satellite data (R² = 0.45, n = 48), even though the remote sensing product showed significant temporal and spatial variability. Crop residue fraction estimated by the model was strongly correlated with field data collected over major crop areas and crop types (R² = 0.74, n = 55), and modelled plant cover fraction was well correlated with that derived from remote sensing data (R² = 0.57, n = 57). Large discrepancies were observed for some samples due to deviation of the actual crop calendar from that estimated using climate normals. National map showing the change in the indicator from 1981 to 2011 reveals changes in crop and residue management practices.     

Dysregulation of exosomal miR-192 and miR-194 expression in lung adenocarcinoma patients

Non-small cell lung cancer (NSCLC) is the main reason of cancer linked mortality and around 80% of cases diagnosed in advanced stage. Therefore current study designed to evaluate the deregulation of miRNA-194 and miRNA-192 in different body fluid of Non small cell lung cancer participants. Present study recruited newly diagnosed histopathologically confirmed. It was observed that the 40% NSCLC participants showed elevated miR-194 expression and 60% NSCLC participants showed reduced miR-194 expression in serum sample while in Bronchial wash, only 20% NSCLC participants showed elevated miR-194 expression while 80% showed reduced miR-194 expression (p = 0.003). It was found that the 54% NSCLC participants showed elevated miR-192 expression and 55% NSCLC participants showed reduced miR-192 expression in serum sample while In Bronchial wash sample, only 25% NSCLC participants showed high miR-192 expression while 75% showed low miR-192 expression (P = 0.0004). Expression of miR-194 was significantly associated with TNM stages (p < 0.0001, p < 0.0001), distant organ metastases (p < 0.0001, p < 0.0001), pathological grade (p = 0.0009, p = 0.0005) among serum sample and bronchial wash sample. Same observation was found with expression of miR-192 and it was significantly associated with TNM stages (p < 0.0001, p < 0.0001), distant organ metastases (p < 0.0001, p < 0.0001), pathological grade (p = 0.006, p = 0.001) among serum sample and bronchial wash sample. It was observed that the NSCLC participants who had high serum based miR-194 expression showed 22 months of overall median survival while low expression of serum based miR-194 expression showed 18 months of overall median survival. Present study suggests that decreased expression of miR-194 and miR-192 was significantly associated with different clinical features of NSCLC cases. However, significantly higher number of NSCLC cases showed low expression of miR-194 and miR-192 in bronchial lavage sample. Decreased poor overall survival was found to be associated with bronchial wash sample with respect to low miR-194 and miR-192 expression while NSCLC participants showed better overall survival with high miR-194 and miR-192 expression. This suggested decreased expression of miR-192 and miR-194 expression could be the potential prognostic marker among NSCLC participants.     

Downregulation of miR-192 causes hepatic steatosis and lipid accumulation by inducing SREBF1: Novel mechanism for bisphenol A-triggered non-alcoholic fatty liver disease

Exposure to Bisphenol A (BPA) has been associated with the development of nonalcoholic fatty liver disease (NAFLD) but the underlying mechanism remains unclear. Given that microRNA (miRNA) is recognized as a key regulator of lipid metabolism and a potential mediator of environmental cues, this study was designed to explore whether exposure to BPA-triggered abnormal steatosis and lipid accumulation in the liver could be modulated by miR-192. We showed that male post-weaning C57BL/6 mice exposed to 50 μg/kg/day of BPA by oral gavage for 90 days displayed a NAFLD-like phenotype. In addition, we found in mouse liver and human HepG2 cells that BPA-induced hepatic steatosis and lipid accumulation were associated with decreased expression of miR-192, upregulation of SREBF1 and a series of genes involved in de novo lipogenesis. Downregulation of miR-192 in BPA-exposed hepatocytes could be due to defective pre-miR-192 processing by DROSHA. Using HepG2 cells, we further confirmed that miR-192 directly acted on the 3′UTR of SREBF1, contributing to dysregulation of lipid homeostasis in hepatocytes. MiR-192 mimic and lentivirus-mediated overexpression of miR-192 improved BPA-induced hepatic steatosis by suppressing SREBF1. Lastly, we noted that lipid accumulation was not a strict requirement for developing insulin resistance in mice after BPA treatment. In conclusion, this study demonstrated a novel mechanism in which NAFLD associated with BPA exposure arose from alterations in the miR-192-SREBF1 axis.     

Índice triglicéridos y glucosa: un indicador útil de insulinorresistencia

IntroductionInsulin resistance assessment requires sophisticated methodology of difficult application. Therefore, different estimators for this condition have been suggested. The aim of this study was to evaluate the triglycerides and glucose (TyG) index as a marker of insulin resistance and to compare it to the triglycerides/HDL cholesterol ratio (TG/HDL-C), in subjects with and without metabolic syndrome (MS).Material and methodsAn observational, cross-sectional study was conducted on 525 adults of a population from Bahia Blanca, Argentina, who were divided into two groups: with MS (n = 89) and without MS (n = 436). The discriminating capacities for MS of the TyG index, calculated as Ln (TG [mg/dL] x glucose [mg/dL]/2), and the TG/HDL-C ratio were evaluated. Pre-test probability for MS was 30%.ResultsThe mean value of the TyG index was higher in the group with MS as compared to the group without MS and its correlation with the TG/HDL-C ratio was good. The cut-off values for MS in the overall population were 8.8 for the TyG index (sensitivity = 79%, specificity = 86%), and 2.4 for the TG/HDL-C ratio (sensitivity = 88%, specificity = 72%). The positive likelihood ratios and post-test probabilities for these parameters were 5.8 vs 3.1 and 72% vs 58% respectively. The cut-off point for the TyG index was 8.8 in men and 8.7 in women; the respective values for TG/C-HDL were 3.1 in men and 2.2 in women.ConclusionsThe TyG index was a good discriminant of MS. Its simple calculation warrants its further study as an alternative marker of insulin resistance.     

Association of serum amyloid A levels with adipocyte size and serum levels of adipokines: Differences between men and women

The aim of this study was to characterize the association between adipocyte enlargement and circulating levels of serum amyloid A (SAA). Furthermore, we wanted to search for possible associations with measures of glycemic control and levels of circulating adipokines and/or inflammatory markers in men and women with a large range in body mass index. The study cohort consisted of 167 subjects, 114 non-diabetic and 53 with Type 2 diabetes. Adipocyte diameter as well as circulating levels of SAA, C-reactive protein (CRP), adiponectin, leptin, interleukin-6, tumor necrosis factor alpha, glucose and insulin were measured. Women had higher serum levels of SAA than men (p = 0.044). SAA levels were weakly but positively correlated with BMI (p = 0.043) and % body fat (p = 0.027) in all subjects as well as subcutaneous adipocyte diameter (p = 0.034) in women. Furthermore, in all subjects we found correlations between SAA levels and levels of CRP (p < 0.001), interleukin-6 (p < 0.001), leptin (p = 0.003), insulin (p = 0.006), HbA1c (p = 0.02) and HOMA-IR (p = 0.002). A majority of the correlations were strongest in women. In conclusion, serum levels of SAA are strongly correlated with serum levels of inflammatory markers as well as measures of glycemic control. There seems to be large sex differences in these associations suggesting that sex-specific factors need to be considered when analyzing SAA levels in relation to metabolic disease.     

MicroRNA miR-7 is preferentially expressed in endocrine cells of the developing and adult human pancreas

MicroRNAs (miRNA) are small non-coding RNAs that inhibit gene expression through binding to complementary messenger RNA sequences. miRNAs have been predicted to target genes important for pancreas development, proper endocrine cell function and metabolism. We previously described that miRNA-7 (miR-7) was the most abundant and differentially expressed islet miRNA, with 200-fold higher expression in mature human islets than in acinar tissue. Here we have analyzed the temporal and spatial expression of miR-7 in human fetal pancreas from 8 to 22 weeks of gestational age (wga). Human fetal (8–22 wga) and adult pancreases were processed for immunohistochemistry, in situ hybridization, and quantitative RT-PCR of miRNA and mRNA. miR-7 was expressed in the human developing pancreas from around 9 wga and reached its maximum expression levels between 14 and 18 wga, coinciding with the exponential increase of the pancreatic endocrine hormones. Throughout development miR-7 expression was preferentially localized to endocrine cells and its expression persisted in the adult pancreas. The present study provides a detailed analysis of the spatiotemporal expression of miR-7 in developing human pancreas. The specific localization of miR-7 expression to fetal and adult endocrine cells indicates a potential role for miR-7 in endocrine cell differentiation and/or function. Future functional studies of a potential role for miR-7 function in islet cell differentiation and physiology are likely to identify novel targets for the treatment of diabetes and will lead to the development of improved protocols for generating insulin-producing cells for cell replacement therapy.     

Validation of a free software for unsupervised assessment of abdominal fat in MRI

PurposeTo demonstrate the accuracy of an unsupervised (fully automated) software for fat segmentation in magnetic resonance imaging. The proposed software is a freeware solution developed in ImageJ that enables the quantification of metabolically different adipose tissues in large cohort studies.MethodsThe lumbar part of the abdomen (19 cm in craniocaudal direction, centered in L3) of eleven healthy volunteers (age range: 21–46 years, BMI range: 21.7–31.6 kg/m²) was examined in a breath hold on expiration with a GE T1 Dixon sequence. Single-slice and volumetric data were considered for each subject. The results of the visceral and subcutaneous adipose tissue assessments obtained by the unsupervised software were compared to supervised segmentations of reference. The associated statistical analysis included Pearson correlations, Bland-Altman plots and volumetric differences (VD_%).ResultsValues calculated by the unsupervised software significantly correlated with corresponding supervised segmentations of reference for both subcutaneous adipose tissue – SAT (R = 0.9996, p < 0.001) and visceral adipose tissue – VAT (R = 0.995, p < 0.001). Bland-Altman plots showed the absence of systematic errors and a limited spread of the differences. In the single-slice analysis, VD_% were (1.6 ± 2.9)% for SAT and (4.9 ± 6.9)% for VAT. In the volumetric analysis, VD_% were (1.3 ± 0.9)% for SAT and (2.9 ± 2.7)% for VAT.ConclusionsThe developed software is capable of segmenting the metabolically different adipose tissues with a high degree of accuracy. This free add-on software for ImageJ can easily have a widespread and enable large-scale population studies regarding the adipose tissue and its related diseases.     

Hígado graso no alcohólico y su asociación con variables clínicas y bioquímicas en niños y adolescentes obesos: efecto de un año de intervención en el estilo de vida

ObjectiveTo study the frequency of non-alcoholic fatty liver disease (NAFLD), its relationship to clinical and biochemical variables, and the effect 12-month's lifestyle intervention in obese children and adolescents.MethodsThirty-six obese patients aged 7 to 18 years, 42% female and 58% male, 72.2% prepubertal and 27.8% pubertal, were selected. Anthropometric measurements and glucose, insulin (baseline and after a glucose load), lipid profile, C-reactive protein, and aminotransferase tests were performed before and 12 months after dietary and physical activity intervention. Liver ultrasound was performed to determine the presence of NAFLD.ResultsNAFLD was found in 66.7% (n = 24), and was mild in 30.6%, moderate in 27.8%, and severe in 8.3%. Subjects with NAFLD had higher body mass index (BMI, p = 0.007), waist (p = 0.005), fat area (p = 0.002), basal insulin (p = 0.01), and HOMA-IR (p = 0.008) values and lower QUICKI (p = 0.02) values than those with no NAFLD. After intervention, physical activity increased (p = 0.0001) and calorie intake remained unchanged. NAFLD disappeared in 9 patients (37.5%, p = 0.02) and disease severity decreased in 3 patients (12.5%). In addition, BMI Z-score (p = 0.005), fat area (p = 0.0001), basal insulin (p < 0.05), insulin resistance (p < 0.005), lipid profile (p < 0.03), and transaminases decreased. Weight loss was the main variable accounting for NAFLD improvement.ConclusionThis group of obese children and adolescents showed a high frequency of NAFLD. The lifestyle intervention with weight reduction is effective for the treatment of NAFLD.     

Identification of reference microRNAs and suitability of archived hemopoietic samples for robust microRNA expression profiling

In many cancers, including neuroblastoma, microRNA (miRNA) expression profiling of peripheral blood (PB) and bone marrow (BM) may increase understanding of the metastatic process and lead to the identification of clinically informative biomarkers. The quality of miRNAs in PB and BM samples archived in PAXgene? blood RNA tubes from large-scale clinical studies and the identity of reference miRNAs for standard reporting of data are to date unknown. In this study, we evaluated the reliability of expression profiling of 377 miRNAs using quantitative polymerase chain reaction (qPCR) in PB and BM samples (n = 90) stored at ?80 °C for up to 5 years in PAXgene? blood RNA tubes. There was no correlation with storage time and variation of expression for any single miRNA (r < 0.50). The profile of miRNAs isolated as small RNAs or co-isolated with small/large RNAs was highly correlated (r = 0.96). The mean expression of all miRNAs and the geNorm program identified miR-26a, miR-28-5p, and miR-24 as the most stable reference miRNAs. This study describes detailed methodologies for reliable miRNA isolation and profiling of PB and BM, including reference miRNAs for qPCR normalization, and demonstrates the suitability of clinical samples archived at ?80 °C into PAXgene? blood RNA tubes for miRNA expression studies.     

SAR and optimization of thiazole analogs as potent stearoyl-CoA desaturase inhibitors

Elevated stearoyl-CoA desaturase (SCD) activity has been linked to a number of metabolic disorders including obesity and type II diabetes. Compound 3j, a potent SCD inhibitor (human HepG2 IC₅₀ = 1 nM) was identified from the optimization of a lead thiazole compound MF-152 with over 100-fold improvement in potency. In a 4-week chronic oral dosing at 0.2 mg/kg, 3j gave a robust 24% prevention of body weight gain in mice fed on a high fat diet accompanied with an improved metabolic profile on insulin and glucose levels.     

Enhancement in liver SREBP-1c/PPAR-α ratio and steatosis in obese patients: Correlations with insulin resistance and n-3 long-chain polyunsaturated fatty acid depletion

Sterol receptor element-binding protein-1c (SREBP-1c) and peroxisome proliferator-activated receptor-α (PPAR-α) mRNA expression was assessed in liver as signaling mechanisms associated with steatosis in obese patients. Liver SREBP-1c and PPAR-α mRNA (RT-PCR), fatty acid synthase (FAS) and carnitine palmitoyltransferase-1a (CPT-1a) mRNA (real-time RT-PCR), and n-3 long-chain polyunsaturated fatty acid (LCPUFA)(GLC) contents, plasma adiponectin levels (RIA), and insulin resistance (IR) evolution (HOMA) were evaluated in 11 obese patients who underwent subtotal gastrectomy with gastro-jejunal anastomosis in Roux-en-Y and 8 non-obese subjects who underwent laparoscopic cholecystectomy (controls). Liver SREBP-1c and FAS mRNA levels were 33% and 70% higher than control values (P < 0.05), respectively, whereas those of PPAR-α and CPT-1a were 16% and 65% lower (P < 0.05), respectively, with a significant 62% enhancement in the SREBP-1c/PPAR-α ratio. Liver n-3 LCPUFA levels were 53% lower in obese patients who also showed IR and hipoadiponectinemia over controls (P < 0.05). IR negatively correlated with both the hepatic content of n-3 LCPUFA (r = ? 0.55; P < 0.01) and the plasma levels of adiponectin (r = ? 0.62; P < 0.005). Liver SREBP-1c/PPAR-α ratio and n-3 LCPUFA showed a negative correlation (r = ? 0.48; P < 0.02) and positive associations with either HOMA (r = 0.75; P < 0.0001) or serum insulin levels (r = 0.69; P < 0.001). In conclusion, liver up-regulation of SREBP-1c and down-regulation of PPAR-α occur in obese patients, with enhancement in the SREBP-1c/PPAR-α ratio associated with n-3 LCPUFA depletion and IR, a condition that may favor lipogenesis over FA oxidation thereby leading to steatosis.     

Circulating levels of irisin in patients with anorexia nervosa and different stages of obesity – Correlation with body mass index

Irisin was recently identified as cleavage product of fibronectin type III domain containing 5 (FNDC5) and shown to increase energy expenditure in mice and humans and therefore was discussed as potential treatment option in obesity. However, the regulation of irisin under conditions of severely altered body weight such as anorexia nervosa and obesity remains to be investigated. We analyzed circulating irisin levels over a broad spectrum of body weight in 40 patients with anorexia nervosa (mean body mass index, BMI 12.6 ± 0.7 kg/m²), normal weight controls (22.6 ± 0.9 kg/m²) and obese patients with BMI of 30–40 (36.9 ± 1.2 kg/m²), 40–50 (44.9 ± 1.1 kg/m²) and >50 (70.1 ± 2.7 kg/m², n = 8/group). Correlation analyses were performed between irisin and different body indices, parameters of body composition and hormones involved in various homeostatic processes. Obese patients showed higher circulating irisin levels compared to normal weight and anorexic patients (p < 0.05) resulting in a correlation of irisin with body weight (r = 0.47, p < 0.01) and BMI (r = 0.50, p < 0.001). Plasma irisin was also positively correlated with fat mass (r = 0.48, p < 0.01), body cell mass (r = 0.45, p < 0.01) and fat free mass (r = 0.40, p < 0.05). Insulin levels were positively correlated with irisin (r = 0.45, p < 0.01), whereas circulating ghrelin, cortisol, thyroid-stimulating hormone or C-reactive protein were not (p > 0.05). These data indicate that circulating irisin is affected under conditions of altered BMI with highest levels in severely obese patients. The increase of irisin under conditions of obesity may indicate a physiological function to improve glucose tolerance which is often impaired in obese subjects.     

Body mass index,iron absorption and iron status in childbearing age women

BackgroundThe prevalence of obesity has increased at an alarming rate worldwide. Some studies have observed an association between iron (Fe) deficiency (ID) and obesity, however more research is needed.ObjectiveTo assess whether body mass index (BMI) is associated with both Fe absorption and Fe status.MethodsA cross sectional sample of 318 Chilean childbearing age women was studied. The women received either a single dose of 0.5 mg of Fe (n = 137, group 1) or 3 mg of Fe plus ascorbic acid (1:2 molar ratio) (n = 181, group 2), both as FeSO₄ with labeled radioisotopes. Fe absorption was assessed through radio Fe erythrocyte incorporation. Fe status was determined by hemoglobin (Hb), mean corpuscular volume, serum Fe, total iron binding capacity, transferrin saturation, erythrocyte Zn protoporphyrin and serum ferritin (SF).Results29%, 47% and 24% of the women were classified as normal, overweight or obese, respectively. Fe absorption was significantly lower in obese women (p < 0.05). In group 1, the geometric mean and range ±1 SD of the percentage of Fe absorption for normal-weight women was 32.9% vs. 19.7% in obese. For group 2, this percentage was 36% vs. 30%, respectively (2-way ANOVA: BMI classification and Fe dose p < 0.05; interaction p = 0.34). Although Fe absorption was lower in obese women, they had higher SF (p < 0.01) and Hb (p < 0.05) concentrations.ConclusionAlthough we did not observe a relationship between BMI and Fe status, obese women displayed lower Fe absorption compared with overweight and normal weight women, possibly due to subclinical inflammation associated with obesity.     

Role of microRNA-27a in down-regulation of angiogenic factor AGGF1 under hypoxia associated with high-grade bladder urothelial carcinoma

Hypoxia stimulates angiogenesis under a variety of pathological conditions, including malignant tumors by inducing expression of angiogenic factors such as VEGFA. Surprisingly, here we report significant association between down-regulation of a new angiogenic factor AGGF1 and high-grade urothelial carcinoma. The proportion of strong AGGF1 expression cases was significantly lower in the high-grade urothelial carcinoma group than that in the low-grade urothelial carcinoma group (P = 1.40 × 10^− 5) or than that in the normal urothelium tissue group (P = 2.11 × 10^− 4). We hypothesized that tumor hypoxia was responsible for differential expression of the AGGF1 protein in low- and high-grade urothelial carcinomas, and therefore investigated the molecular regulatory mechanism for AGGF1 expression under hypoxia. Under hypoxic conditions, AGGF1 protein levels declined without any change in mRNA levels and protein stability. Hypoxia-induced down-regulation of AGGF1 was mediated by miR-27a. Overexpression of miR-27a suppressed AGGF1 expression through translational inhibition, but not by RNA degradation. Moreover, the hypoxia-induced decrease of AGGF1 expression disappeared after miR-27a expression was inhibited. Furthermore, down-regulation of AGGF1 reduced hypoxia-induced apoptosis in cancer cells. Taken together, the results of this study indicate that (1) hypoxia down-regulates expression of the AGGF1 protein, but not AGGF1 mRNA, by inducing expression of miR-27a; (2) Down-regulation of AGGF1 had an apparent protective role for cancer cells under hypoxia; (3) Down-regulation of the AGGF1 protein confers a significant risk of high-grade human urothelial bladder carcinoma.