MiRNA expression profile of human subcutaneous adipose and during adipocyte differentiation

This is an open-access article distributed under the terms of the Creative Commons Attribution License.-- et al.[Background]: Potential regulators of adipogenesis include microRNAs (miRNAs), small non-coding RNAs that have been recently shown related to adiposity and differentially expressed in fat depots. However, to date no study is available, to our knowledge, regarding miRNAs expression profile during human adipogenesis. Thereby, the aim of this study was to investigate whether miRNA pattern in human fat cells and subcutaneous adipose tissue is associated to obesity and co-morbidities and whether miRNA expression profile in adipocytes is linked to adipogenesis. [Methodology/Principal Findings]: We performed a global miRNA expression microarray of 723 human and 76 viral mature miRNAs in human adipocytes during differentiation and in subcutaneous fat samples from non-obese (n=6) and obese with (n=9) and without (n=13) Type-2 Diabetes Mellitus (DM-2) women. Changes in adipogenesis-related miRNAs were then validated by RT-PCR. Fifty of 799 miRNAs (6.2%) significantly differed between fat cells from lean and obese subjects. Seventy miRNAs (8.8%) were highly and significantly up or down-regulated in mature adipocytes as compared to pre-adipocytes. Otherwise, 17 of these 799 miRNAs (2.1%) were correlated with anthropometrical (BMI) and/or metabolic (fasting glucose and/or triglycerides) parameters. We identified 11 miRNAs (1.4%) significantly deregulated in subcutaneous fat from obese subjects with and without DM-2. Interestingly, most of these changes were associated with miRNAs also significantly deregulated during adipocyte differentiation. [Conclusions/Significance]: The remarkable inverse miRNA profile revealed for human pre-adipocytes and mature adipocytes hints at a closely crosstalk between miRNAs and adipogenesis. Such candidates may represent biomarkers and therapeutic targets for obesity and obesity-related complications.This work was supported by research grants from the Ministerio de Educación y Ciencia (MEC) (SAF2008-02073), the Instituto de Salud Carlos III (CIBERObN, CB06/03/0010), and the Hospital Dr. Josep Trueta de Girona.Peer reviewe

Decreased STAMP2 expression in association with visceral adipose tissue dysfunction

10 páginas, 6 figuras, 2 tablas.-- et al.[Context]: Six-transmembrane protein of prostate 2 (STAMP2) is a counter-regulator of inflammation and insulin resistance according to findings in mice. However, there have been contradictory reports in humans. [Objective]: We aimed to explore STAMP2 in association with inflammatory and metabolic status of human obesity. [Design, Patients, and Methods]: STAMP2 gene expression was analyzed in adipose tissue samples (171 visceral and 67 sc depots) and during human preadipocyte differentiation. Human adipocytes were treated with macrophage-conditioned medium, TNF-α, and rosiglitazone. [Results]: In visceral adipose tissue, STAMP2 gene expression was significantly decreased in obese subjects, mainly in obese subjects with type 2 diabetes. STAMP2 gene expression and protein were significantly and inversely associated with obesity phenotype measures (body mass index, waist, hip, and fat mass) and obesity-associated metabolic disturbances (systolic blood pressure and fasting glucose). In addition, STAMP2 gene expression was positively associated with lipogenic (FASN, ACC1, SREBP1, THRSP14, TRα, and TRα1), CAV1, IRS1, GLUT4, and CD206 gene expression. In sc adipose tissue, STAMP2 gene expression was not associated with metabolic parameters. In both fat depots, STAMP2 gene expression in stromovascular cells was significantly higher than in mature adipocytes. STAMP2 gene expression was significantly increased during the differentiation process in parallel to adipogenic genes, being increased in preadipocytes derived from lean subjects. Macrophage-conditioned medium (25%) and TNF-α (100 ng/ml) administration increased whereas rosiglitazone (2 μM) decreased significantly STAMP2 gene expression in human differentiated adipocytes. [Conclusions]: Decreased STAMP2 expression (mRNA and protein) might reflect visceral adipose dysfunction in subjects with obesity and type 2 diabetes.Peer reviewe

Inverse relation between FASN expression in human adipose tissue and the insulin resistance level

<p>Abstract</p> <p>Background</p> <p>Adipose tissue is a key regulator of energy balance playing an active role in lipid storage and may be a dynamic buffer to control fatty acid flux. Just like PPARγ, fatty acid synthesis enzymes such as FASN have been implicated in almost all aspects of human metabolic alterations such as obesity, insulin resistance or dyslipemia. The aim of this work is to investigate how FASN and PPARγ expression in human adipose tissue is related to carbohydrate metabolism dysfunction and obesity.</p> <p>Methods</p> <p>The study included eighty-seven patients which were classified according to their BMI and to their glycaemia levels in order to study FASN and PPARγ gene expression levels, anthropometric and biochemical variables.</p> <p>Results</p> <p>The main result of this work is the close relation between FASN expression level and the factors that lead to hyperglycemic state (increased values of glucose levels, HOMA-IR, HbA1c, BMI and triglycerides). The correlation of the enzyme with these parameters is inversely proportional. On the other hand, PPARγ is not related to carbohydrate metabolism.</p> <p>Conclusions</p> <p>We can demonstrate that FASN expression is a good candidate to study the pathophysiology of type II diabetes and obesity in humans.</p

The MRC1/CD68 ratio is positively associated with adipose tissue lipogenesis and with muscle mitochondrial gene expression in humans

This is an open-access article distributed under the terms of the Creative Commons Attribution License.[Background]: Alternative macrophages (M2) express the cluster differentiation (CD) 206 (MCR1) at high levels. Decreased M2 in adipose tissue is known to be associated with obesity and inflammation-related metabolic disturbances. Here we aimed to investigate MCR1 relative to CD68 (total macrophages) gene expression in association with adipogenic and mitochondrial genes, which were measured in human visceral [VWAT, n = 147] and subcutaneous adipose tissue [SWAT, n = 76] and in rectus abdominis muscle (n = 23). The effects of surgery-induced weight loss were also longitudinally evaluated (n = ).[Results]: MCR1 and CD68 gene expression levels were similar in VWAT and SWAT. A higher proportion of CD206 relative to total CD68 was present in subjects with less body fat and lower fasting glucose concentrations. The ratio MCR1/CD68was positively associated with IRS1gene expression and with the expression of lipogenic genes such as ACACA, FASN and THRSP, even after adjusting for BMI. The ratio MCR1/CD68 in SWAT increased significantly after the surgery-induced weight loss (+44.7%; p = 0.005) in parallel to the expression of adipogenic genes. In addition, SWAT MCR1/CD68ratio was significantly associated with muscle mitochondrial gene expression (PPARGC1A, TFAM and MT-CO3). AT CD206 was confirmed by immunohistochemistry to be specific of macrophages, especially abundant in crown-like structures. [Conclusion]: A decreased ratio MCR1/CD68 is linked to adipose tissue and muscle mitochondrial dysfunction at least at the level of expression of adipogenic and mitochondrial genes. © 2013 moreno-navarrete et al.This work was supported by grant SAF-2009-10461 and grant PI11-00214 from the Ministerio de Economía y Competitividad, Spain.Peer Reviewe

Study of caveolin-1 gene expression in whole adipose tissue and its subfractions and during differentiation of human adipocytes

<p>Abstract</p> <p>Context</p> <p>Caveolins are 21-24 kDa integral membrane proteins that serve as scaffolds to recruit numerous signaling molecules. Specific subclasses of caveolae carry out specific functions in cell metabolism. In particular, triglycerides are synthesized at the site of fatty acid entry in one of these caveolae classes.</p> <p>Objective and Methods</p> <p>We studied the expression of caveolin-1 (<it>CAV-1</it>) gene in association with metabolic variables in 90 visceral and 55 subcutaneous adipose tissue samples from subjects with a wide range of fat mass, in the stromovascular fraction (SVC) and isolated adipocytes, and during differentiation of human adipocytes.</p> <p>Results</p> <p><it>CAV-1 </it>gene expression was significantly decreased in visceral adipose tissue (v-<it>CAV-1</it>) of obese subjects. v-<it>CAV-1 </it>was positively associated with several lipogenic genes such as acetyl-coA carboxylase (<it>ACACA</it>, r = 0.34, p = 0.004) and <it>spot-14 </it>(r = 0.33, p = 0.004). In non-obese subjects v-<it>CAV-1 </it>also correlated with fatty acid synthase (<it>FAS</it>, r = 0.60, p < 0.0001). Subcutaneous (sc) adipose tissue (s<it>c-CAV-1</it>) gene expression was not associated with these lipogenic factors when obese and non-obese subjects were studied together. In obese subjects, however, sc-<it>CAV-1 </it>was associated with fatty acid synthase (<it>FAS</it>, r = 0.36, p = 0.02), sterol regulatory element binding protein-1c (<it>SREBP-1c </it>(r = 0.58, p < 0.0001), <it>ACACA </it>(r = 0.33, p = 0.03), <it>spot-14 </it>(r = 0.36, p = 0.02), <it>PPAR-γ co-activator-1 </it>(<it>PGC-1</it>, r = 0.88, n = 19). In these obese subjects, <it>sc-CAV-1 </it>was also associated with fasting triglycerides (r = -0.50, p < 0.0001).</p> <p><it>CAV-1 </it>expression in mature adipocytes was significantly higher than in stromal vascular cells. <it>CAV-1 </it>gene expression in adipocytes from subcutaneous adipose tissue (but not in adipocytes from visceral adipose tissue) was significatively associated with fasting triglycerides. <it>CAV-1 </it>gene expression did not change significantly during differentiation of human preadipocytes from lean or obese subjects despite significant increase of FAS gene expression.</p> <p>Conclusion</p> <p>Decreased <it>CAV-1 </it>gene expression was simultaneously linked to increased triglycerides and decreased lipogenic gene expression among obese subjects, paralleling the observations of hypertriglyceridemia in <it>CAV-1 </it>knockout mice. However, the regulation of <it>CAV-1 </it>gene expression seems independent of the adipogenic program.</p

Trust and contextual engagement with the PEPPER system: The qualitative findings of a clinical feasibility study

Background and aims. PEPPER (Patient Empowerment through Predictive PERsonalised decision support) is an EU-funded research project which aims to improve self-management of type 1 diabetes (T1D). The system comprises an AI insulin bolus recommender, coupled with a safety system. The aim of the qualitative arm of this clinical feasibility study was to examine the context of participants’ interaction with the PEPPER system and identify incidents where bolus recommendations were trusted and accepted. Methods. This was a multicentre (UK and Spain) non-randomised open-labelled 6-week pilot study. Thirteen adults with T1D participated in weekly telephone interviews to explore the context of their interactions and responses to PEPPER. Data was thematically analysed through conceptual frameworks for engagement with healthcare digital behaviour change interventions. Results. Participants reported their key interactions as responding to PEPPER bolus recommendations, inputting carbohydrate values, interpreting continuous glucose monitoring (CGM) values through visualization of personal data and dealing with safety alarms. Two themes were associated with trust and engagement with the system; ‘feeling monitored’ and ‘feeling in control’. The incidents where participants trusted PEPPER also enhanced personal expertise of T1D through insights provided by the safety system such as low glucose basal insulin for pump users. Benefits were balanced against technical challenges of the system, which were used to improve the PEPPER application and enhance user experience. Conclusion. Some participants suggested that even access to PEPPER for a temporary period could positively influence self-management strategies. Contextual interviewing is a valuable tool in mobile application development for diabetes decision support systems

Updating known distribution models for forecasting climate change impact on endangered species

To plan endangered species conservation and to design adequate management programmes, it is necessary to predict their distributional response to climate change, especially under the current situation of rapid change. However, these predictions are customarily done by relating de novo the distribution of the species with climatic conditions with no regard of previously available knowledge about the factors affecting the species distribution. We propose to take advantage of known species distribution models, but proceeding to update them with the variables yielded by climatic models before projecting them to the future. To exemplify our proposal, the availability of suitable habitat across Spain for the endangered Bonelli’s Eagle (Aquila fasciata) was modelled by updating a pre-existing model based on current climate and topography to a combination of different general circulation models and Special Report on Emissions Scenarios. Our results suggested that the main threat for this endangered species would not be climate change, since all forecasting models show that its distribution will be maintained and increased in mainland Spain for all the XXI century. We remark on the importance of linking conservation biology with distribution modelling by updating existing models, frequently available for endangered species, considering all the known factors conditioning the species’ distribution, instead of building new models that are based on climate change variables only.Ministerio de Ciencia e Innovación and FEDER (project CGL2009-11316/BOS

The APOA1BP-SREBF-NOTCH axis is associated with reduced atherosclerosis risk in morbidly obese patients

Background and Aims: Atherosclerosis is characterized by an inflammatory disease linked to excessive lipid accumulation in the artery wall. The Notch signalling pathway has been shown to play a key regulatory role in the regulation of inflammation. Recently, in vitro and pre-clinical studies have shown that apolipoprotein A-I binding protein (AIBP) regulates cholesterol metabolism (SREBP) and NOTCH signalling (haematopoiesis) and may be protective against atherosclerosis, but the evidence in humans is scarce. Methods: We evaluated the APOA1BP-SREBF-NOTCH axis in association with atherosclerosis in two well-characterized cohorts of morbidly obese patients (n = 78) within the FLORINASH study, including liver transcriptomics, 1H-NMR plasma metabolomics, high-resolution ultrasonography evaluating carotid intima-media thickness (cIMT), and haematological parameters. Results: The liver expression levels of APOA1BP were associated with lower cIMT and leukocyte counts, a better plasma lipid profile and higher circulating levels of metabolites associated with lower risk of atherosclerosis (glycine, histidine and asparagine). Conversely, liver SREBF and NOTCH mRNAs were positively associated with atherosclerosis, liver steatosis, an unfavourable lipid profile, higher leukocytes and increased levels of metabolites linked to inflammation and CVD such as branched-chain amino acids and glycoproteins. APOA1BP and NOTCH signalling also had a strong association, as revealed by the negative correlations among APOA1BP expression levels and those of all NOTCH receptors and jagged ligands. Conclusions: We here provide the first evidence in human liver of the putative APOA1BP-SREBF-NOTCH axis signalling pathway and its association with atherosclerosis and inflammation

How is COVID-19 affecting patients with obsessive-compulsive disorder? A longitudinal study on the initial phase of the pandemic in a Spanish cohort

Background: Although the consequences of the COVID-19 pandemic on emotional health are evident, little is known about its impact on patients with obsessive-compulsive disorder (OCD). Methods: One hundred and twenty-seven patients with OCD who attended a specialist OCD Clinic in Barcelona, Spain, were assessed by phone from April 27 to May 25, 2020, during the early phase of the pandemic, using the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) and a structured interview that collected clinical and sociodemographic information. Results were compared with those for 237 healthy controls from the same geographic area who completed an online survey. Results: Although 65.3% of the patients with OCD described a worsening of their symptoms, only 31.4% had Y-BOCS scores that increased >25%. The risk of getting infected by SARS-CoV2 was reported as a new obsession by 44.8%, but this only became the main obsessive concern in approximately 10% of the patients. Suicide-related thoughts were more frequent among the OCD cohort than among healthy controls. The presence of prepandemic depression, higher Y-BOCS scores, contamination/washing symptoms, and lower perceived social support all predicted a significantly increased risk of OCD worsening. Conclusions: Most patients with OCD appear to be capable of coping with the emotional stress of the COVID-19 outbreak and its consequences during the initial phase of the pandemic. Nevertheless, the current crisis constitutes a risk factor for a significant worsening of symptoms and suicidal ideation. Action is needed to ensure effective and individualized follow-up care for patients with OCD in the COVID-19 era