Examinando por Autor "Ortega Moreno, Lorena"

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Association of resistin polymorphisms with resistin levels and lipid profile in children
(Springer, 2014-08-06) Ortega Moreno, Lorena; Navarro, Pilar; Riestra, Pía; Gavela-Pérez, Teresa; Soriano-Guillén, Leandro; Garcés, Carmen
Previous research has found a correlation between resistin and lipid level variations. Polymorphisms in the resistin gene (RETN) could be involved in this relationship, but the results of the different studies are contradictory. The aim of this study was to examine the association between resistin and lipid levels, and to determine whether resistin polymorphisms are associated with resistin levels and lipid profile in prepubertal children and adolescents. The single nucleotide polymorphisms (SNPs) rs1862513 and rs10401670 were analyzed in 442 randomly selected 6- to 8-year-old children and 827 children aged 12-16 years. Anthropometric data were recorded. Lipid profile was determined using standard methods. Serum resistin levels were measured using a multiplexed bead immunoassay. Resistin polymorphisms were determined by TaqMan(®) allelic discrimination assays. A relationship was found between serum levels of resistin and the SNP rs10401670 in 6- to 8-year-old boys. SNP rs10401670 was also related to TC and LDL-cholesterol in 12- to 16-year-old boys and to HDL-C in 12- to 16-year-old girls. SNP rs1862513 was not related to any of the studied variables. Serum resistin levels were significantly and negatively associated with ApoAI levels in 12- to 16-year-old girls. A SNP in the 3'UTR region of RETN (rs10401670) is associated with resistin levels and lipid profile in children, showing different associations depending on age and gender.
Biological Treatments in Inflammatory Bowel Disease: A Complex Mix of Mechanisms and Actions
(MDPI, 2021-08-10) Ortega Moreno, Lorena; Fernández-Tomé, Samuel; Abalo, Raquel
Inflammatory bowel disease (IBD) is a chronic disease that requires lifelong medication and whose incidence is increasing over the world. There is currently no cure for IBD, and the current therapeutic objective is to control the inflammatory process. Approximately one third of treated patients do not respond to treatment and refractoriness to treatment is common. Therefore, pharmacological treatments, such as monoclonal antibodies, are urgently needed, and new treatment guidelines are regularly published. Due to the extremely important current role of biologics in the therapy of IBD, herein we have briefly reviewed the main biological treatments currently available. In addition, we have focused on the mechanisms of action of the most relevant groups of biological agents in IBD therapy, which are not completely clear but are undoubtfully important for understanding both their therapeutic efficacy and the adverse side effects they may have. Further studies are necessary to better understand the action mechanism of these drugs, which will in turn help us to understand how to improve their efficacy and safety. These studies will hopefully pave the path for a personalized medicine
Evidence of a causal relationship between high serum adiponectin levels and increased cardiovascular mortality rate in patients with type 2 diabetes
(BioMed Central, 2016) Ortega Moreno, Lorena; Copetti, Massimiliano; Fontana, Andrea; De Bonis, Concetta; Salvemini, Lucia; Trischitta, Vincenzo; Menzaghi, Claudia
Background Despite its beneficial role on insulin resistance and atherosclerosis, adiponectin has been repeatedly reported as an independent positive predictor of cardiovascular mortality. Methods A Mendelian randomization approach was used, in order to evaluate whether such counterintuitive association recognizes a cause-effect relationship. To this purpose, single nucleotide polymorphism rs822354 in the ADIPOQ locus which has been previously associated with serum adiponectin at genome-wide level, was used as an instrument variable. Our investigation was carried out in the Gargano Heart Study-prospective design, comprising 356 patients with type 2 diabetes, in whom both total and high molecular weight (HMW) adiponectin were measured and cardiovascular mortality was recorded (mean follow-up = 5.4 ± 2.5 years; 58 events/1922 person-year). Results The A allele of rs822354 was associated with both total and HMW adiponectin [β (SE) = 0.10 (0.042), p = 0.014 and 0.17 (0.06), p = 0.003; respectively]. In a Poisson model comprising age, sex, smoking habits, BMI, HbA1c, total cholesterol, HDL-cholesterol, triglycerides, insulin therapy and hypertension, both rs822354 (IRR = 1.94, 95 % CI 1.23–3.07; p = 0.005), as well as the genetic equivalent of total adiponectin change (IRR = 1.07, 95 % CI 1.02–1.12; p = 0.003) were significantly associated with cardiovascular mortality. The observed genetic effect was significantly greater than that exerted by the genetic equivalent change of serum adiponectin (p for IRR heterogeneity = 0.012). In the above-mentioned adjusted model, very similar results were obtained when HMW, rather than total, adiponectin was used as the exposure variable of interest. Conclusions Our data suggest that the paradoxical association between high serum adiponectin levels and increased cardiovascular mortality rate is based on a cause-effect relationship, thus pointing to an unexpected deleterious role of adiponectin action/metabolism on atherosclerotic processes.
Gut Microbiota and Dietary Factors as Modulators of the Mucus Layer in Inflammatory Bowel Disease
(MDPI, 2021-09-21) Ortega Moreno, Lorena; Fernández-Tomé, Samuel; Chaparro, María; Gisbert P., Javier
The gastrointestinal tract is optimized to efficiently absorb nutrients and provide a competent barrier against a variety of lumen environmental compounds. Different regulatory mechanisms jointly collaborate to maintain intestinal homeostasis, but alterations in these mechanisms lead to a dysfunctional gastrointestinal barrier and are associated to several inflammatory conditions usually found in chronic pathologies such as inflammatory bowel disease (IBD). The gastrointestinal mucus, mostly composed of mucin glycoproteins, covers the epithelium and plays an essential role in digestive and barrier functions. However, its regulation is very dynamic and is still poorly understood. This review presents some aspects concerning the role of mucus in gut health and its alterations in IBD. In addition, the impact of gut microbiota and dietary compounds as environmental factors modulating the mucus layer is addressed. To date, studies have evidenced the impact of the three-way interplay between the microbiome, diet and the mucus layer on the gut barrier, host immune system and IBD. This review emphasizes the need to address current limitations on this topic, especially regarding the design of robust human trials and highlights the potential interest of improving our understanding of the regulation of the intestinal mucus barrier in IBD.
Human intestinal pro-inflammatory CD11chighCCR2+CX3CR1+ macrophages, but not their tolerogenic CD11c−CCR2−CX3CR1− counterparts, are expanded in inflammatory bowel disease
(Springer Nature, 2018) Bernardo, David; Marin, Alicia C; Fernández-Tomé, Samuel; Montalban-Arqués, Ana; Carrasco, A; Tristan, E; Ortega Moreno, Lorena; Mora-Gutierrez, Irene; Diaz-Guerra, A; Caminero-Fernández, R; Miranda, P; Casals, F; Caldas, M; Jiménez, M; Casabona, Sergio; de la Morena, F; Esteve, M; Santander, Cecilio; Chaparro, María; Gisbert, Javier P.
Although macrophages (Mϕ) maintain intestinal immune homoeostasis, there is not much available information about their subset composition, phenotype and function in the human setting. Human intestinal Mϕ (CD45+HLA-DR+CD14+CD64+) can be divided into subsets based on the expression of CD11c, CCR2 and CX3CR1. Monocyte-like cells can be identified as CD11chighCCR2+CX3CR1+ cells, a phenotype also shared by circulating CD14+ monocytes. On the contrary, their Mϕ-like tissue-resident counterparts display a CD11c−CCR2−CX3CR1− phenotype. CD11chigh monocyte-like cells produced IL-1β, both in resting conditions and after LPS stimulation, while CD11c− Mϕ-like cells produced IL-10. CD11chigh pro-inflammatory monocyte-like cells, but not the others, were increased in the inflamed colon from patients with inflammatory bowel disease (IBD), including Crohn's disease and ulcerative colitis. Tolerogenic IL-10-producing CD11c− Mϕ-like cells were generated from monocytes following mucosal conditioning. Finally, the colonic mucosa recruited circulating CD14+ monocytes in a CCR2-dependent manner, being such capacity expanded in IBD. Mϕ subsets represent, therefore, transition stages from newly arrived pro-inflammatory monocyte-like cells (CD11chighCCR2+CX3CR1+) into tolerogenic tissue-resident (CD11c−CCR2−CX3CR1−) Mϕ-like cells as reflected by the mucosal capacity to recruit circulating monocytes and induce CD11c− Mϕ. The process is nevertheless dysregulated in IBD, where there is an increased migration and accumulation of pro-inflammatory CD11chigh monocyte-like cells.
Immunomodulatory E ect of Gut Microbiota-Derived Bioactive Peptides on Human Immune System from Healthy Controls and Patients with Inflammatory Bowel Disease
(MDPI, 2019) Fernández-Tomé, Samuel; Marin, Alicia C; Ortega Moreno, Lorena; Baldan-Martin, Montse; Mora-Gutierrez, Irene; Lanas-Gimeno, Aitor; Moreno-Monteagudo, Jose Andrés; Santander, Cecilio; Sánchez, Borja; Chaparro, María; Gisbert, Javier P.; Bernardo, David
Bioactive peptides secreted by probiotic Bifidobacterium longum (peptide B7) and opportunistic pathogen Bacteroides fragilis (peptide B12) modulate the intestinal cytokine milieu in health. Here, we characterized their capacity to modulate both the mucosal cytokine production and the phenotype of circulating antigen presenting cells (APCs) in active inflammatory bowel disease (IBD). The IBD mucosa produced higher levels of pro-inflammatory cytokines referred to healthy controls (HCs). Peptides B7 and B12, however, did not ameliorate the mucosal cytokine milieu in IBD. Human circulating APCs (B-cells, monocytes, plasmacytoid dendritic cells (pDCs), and conventional dendritic cells (cDCs)) were characterized by flow cytometry in presence/absence of the peptides. Circulating B-cells, monocytes, and cDCs from IBD patients were more activated than those from HCs. Peptide B7, but not B12, decreased CCR2 expression on all APC subsets from HC, but not IBD patients. Moreover, both peptides tend to further increase their pro-inflammatory profile in IBD. In summary, IBD patients display mucosal and circulating APC pro-inflammatory properties. Peptide B7 immunomodulatory capacity elicited over circulating APCs from HC, but not IBD patients, suggests the presence of disrupted modulatory mechanisms for this peptide in IBD. Future studies should address the effect of bacteria-derived immunomodulatory peptides in non-inflamed (quiescent) IBD patients.
Long Non-Coding RNA Signatures in the Ileum and Colon of Crohn’s Disease Patients and Effect of Anti-TNF-alpha Treatment on Their Modulation
(MDPI, 2023) Baldan-Martin, Montse; Rubín de Célix, Cristina; Orejudo, Macarena; Ortega Moreno, Lorena; Fernández-Tomé, Samuel; Soleto, Irene; Ramírez, Cristina; Arroyo, Ricardo; Fernández, Paloma; Santander, Cecilio; Moreno-Monteagudo, Jose Andrés; Casanova, María José; Casals, Fernando; Casabona, Sergio; Becerro, Irene; Lozano, Juan J; Aransay, Ana Maria; Chaparro, María; Gisbert, Javier P.
Biological therapies only benefit one-third of patients with Crohn’s disease (CD). For this reason, a deeper understanding of the mechanisms by which biologics elicit their effect on intestinal mucosa is needed. Increasing evidence points toward the involvement of long noncoding RNAs (lncRNAs) in the pathogenesis of CD, although their role remains poorly studied. We aimed to characterize lncRNA profiles in the ileum and colon from CD patients and evaluate the effect of anti-TNF-α treatment on their transcription. Terminal ileum and left colon samples from 30 patients (active CD = 10, quiescent CD = 10, and healthy controls (HCs) = 10) were collected for RNA-seq. The patients were classified according to endoscopic activity. Furthermore, biopsies were cultured with infliximab, and their transcriptome was determined by Illumina gene expression array. A total of 678 differentially expressed lncRNAs between the terminal ileum and left colon were identified in HCs, 438 in patients with quiescent CD, and 468 in patients with active CD. Additionally, we identified three new lncRNAs in the ileum associated with CD activity. No differences were observed when comparing the effect of infliximab according to intestinal location, presence of disease (CD vs. HC), and activity (active vs. quiescent). The expression profiles of lncRNAs are associated with the location of intestinal tissue, being very different in the ileum and colon. The presence of CD and disease activity are associated with the differential expression of lncRNAs. No modulatory effect of infliximab has been observed in the lncRNA transcriptome.
Long Non-Coding RNAs and Their Potential Role as Biomarkers in Inflammatory Bowel Disease
(MDPI, 2024-08-13) Ortega Moreno, Lorena; Chaparro, María; Gisbert, Javier P.
Inflammatory bowel disease is a chronic inflammatory disease that encompasses entities such as Crohn’s disease and ulcerative colitis. Its incidence has risen in newly industrialised countries over time, turning it into a global disease. Lately, studies on inflammatory bowel disease have focused on finding non-invasive and specific biomarkers. Long non-coding RNAs may play a role in the pathophysiology of inflammatory bowel disease and therefore they may be considered as potential biomarkers for this disease. In the present article, we review information in the literature on the relationship between long non-coding RNAs and inflammatory bowel disease. We especially focus on understanding the potential function of these RNAs as non-invasive biomarkers, providing information that may be helpful for future studies in the field.
Lunasin Peptide is a Modulator of the Immune Response in the Human Gastrointestinal Tract
(Wiley, 2021-04-22) Fernández-Tomé, Samuel; Indiano-Romacho, Pedro; Mora-Gutiérrez, Irene; Pérez-Rodríguez, Leticia; Ortega Moreno, Lorena; Marin, Alicia C; Baldán-Martín, Montse; Moreno-Monteagudo, Jose Andrés; Santander, Cecilio; Chaparro, María; Hernández-Ledesma, Blanca; Gisbert P., Javier; Bernardo, David
Introduction: Lunasin is a soybean bioactive peptide with a variety of beneficial properties against chronic disorders. However, its effect in human primary intestinal cells remains unknown. Hence, this study aims to characterize its ex vivo biological activity in the human intestinal mucosa. Methods and Results: Human intestinal biopsies, obtained from healthy controls, are ex vivo conditioned with lunasin both in the presence/absence of lipopolysaccharide (LPS). Peptide maintains its stability during biopsy culture by HPLC-MS/MS analysis. Lunasin is bioactive in the human mucosa, as it induces IL-1𝜷, TNF-𝜶, IL-17A, CCL2, and PGE2/COX-2 gene expression together with an increased expression of tolerogenic IL-10 and TGF𝜷, while it also downregulates the expression of iNOS and subunit p65 from NF-𝜿B. Indeed, lunasin also abrogates the LPS-induced pro-inflammatory response, downregulating IL-17A, IFN𝜸, and IL-8 expression, and inducing IL-10 and TGF𝜷 expression. These results are also mirrored in the cell-free culture supernatants at the protein level by Multiplex. Moreover, lunasin further induces a regulatory phenotype and function on human intestinal conventional dendritic cell and macrophage subsets as assessed by flow cytometry. Conclusions: We hereby have characterized lunasin as an immunomodulatory peptide with potential capacity to prevent immune and inflammatory-mediated disorders in the human gastrointestinal tract.
Metabolomics study of COVID-19 patients in four different clinical stages
(2022) Valdés, Alberto; Ortega Moreno, Lorena; Rojo Rello, Silvia; Orduña, Antonio; Bernardo, David; Cifuentes, Alejandro
SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) is the coronavirus strain causing the respiratory pandemic COVID-19 (coronavirus disease 2019). To understand the pathobiology of SARSCoV- 2 in humans it is necessary to unravel the metabolic changes that are produced in the individuals once the infection has taken place. The goal of this work is to provide new information about the altered biomolecule profile and with that the altered biological pathways of patients in different clinical situations due to SARS-CoV-2 infection. This is done via metabolomics using HPLC–QTOF–MS analysis of plasma samples at COVID-diagnose from a total of 145 adult patients, divided into different clinical stages based on their subsequent clinical outcome (25 negative controls (non-COVID); 28 positive patients with asymptomatic disease not requiring hospitalization; 27 positive patients with mild disease defined by a total time in hospital lower than 10 days; 36 positive patients with severe disease defined by a total time in hospital over 20 days and/or admission at the ICU; and 29 positive patients with fatal outcome or deceased). Moreover, follow up samples between 2 and 3 months after hospital discharge were also obtained from the hospitalized patients with mild prognosis. The final goal of this work is to provide biomarkers that can help to better understand how the COVID-19 illness evolves and to predict how a patient could progress based on the metabolites profile of plasma obtained at an early stage of the infection. In the present work, several metabolites were found as potential biomarkers to distinguish between the end-stage and the early-stage (or non-COVID) disease groups. These metabolites are mainly involved in the metabolism of carnitines, ketone bodies, fatty acids, lysophosphatidylcholines/phosphatidylcholines, tryptophan, bile acids and purines, but also omeprazole. In addition, the levels of several of these metabolites decreased to “normal” values at hospital discharge, suggesting some of them as early prognosis biomarkers in COVID-19 at diagnose.
Modelo de riesgo de mortalidad precoz en pacientes ancianos con enfermedad aguda atendidos por servicios de emergencias prehospitalarias
(Sociedad Española de Medicina de Urgencias y Emergencias, 2020-06) Martín-Rodríguez, Francisco; Sanz-García, Ancor; Ortega Moreno, Lorena; del Pozo Vegas, Carlos; Castro-Villamor, Miguel A.; Martín-Conty, José Luis; López-Izquierdo, Raúl; Ortega Rabbione, Guillermo
Objectives: To develop and validate a prehospital risk model to predict early in-hospital mortality (#48 hours) in patients aged 65 years or older. Material and methods: Prospective multicenter observational study in a cohort of patients aged 65 years or older attended by advanced life support emergency services and transferred to 5 Spanish hospitals between April 2018 and July 2019. We collected demographic, clinical and laboratory variables. A risk score was constructed and validated based on the analysis of prehospital variables associated with death within 48 hours. Predictors were selected by logistic regression. Results: A total of 1759 patients were recruited. The median age was 79 years (interquartile range, 72-85 years), and 766 (43.5%) were women. One hundred eight patients (6.1%) died within 48 hours. Predictors in the Prehospital Older Adults Warning Scale (POAWS) were age, systolic blood pressure, temperature, the ratio of oxygen saturation to the fraction of inspired oxygen, score on the Glasgow coma scale, and lactic acid concentration in venous blood. The area under the receiver operating characteristic curve of the model to predict early mortality was 0.853 (95% CI, 0.80-0.91; P<.001). Mortality in patients at high risk (POAWS score, >7) was 69%. Conclusion: The prehospital POAWS score can be used to stratify risk for death within 48 hours in patients aged 65 years or older.
New Pieces for an Old Puzzle: Approaching Parkinson’s Disease from Translatable Animal Models, Gut Microbiota Modulation, and Lipidomics
(2023) Ortega Moreno, Lorena; Bagues, Ana; Martínez, Vicente; Abalo, Raquel
Parkinson’s disease (PD) is a severe neurodegenerative disease characterized by disabling motor alterations that are diagnosed at a relatively late stage in its development, and non-motor symptoms, including those affecting the gastrointestinal tract (mainly constipation), which start much earlier than the motor symptoms. Remarkably, current treatments only reduce motor symptoms, not without important drawbacks (relatively low efficiency and impactful side effects). Thus, new approaches are needed to halt PD progression and, possibly, to prevent its development, including new therapeutic strategies that target PD etiopathogeny and new biomarkers. Our aim was to review some of these new approaches. Although PD is complex and heterogeneous, compelling evidence suggests it might have a gastrointestinal origin, at least in a significant number of patients, and findings in recently developed animal models strongly support this hypothesis. Furthermore, the modulation of the gut microbiome, mainly through probiotics, is being tested to improve motor and non-motor symptoms and even to prevent PD. Finally, lipidomics has emerged as a useful tool to identify lipid biomarkers that may help analyze PD progression and treatment efficacy in a personalized manner, although, as of today, it has only scarcely been applied to monitor gut motility, dysbiosis, and probiotic effects in PD. Altogether, these new pieces should be helpful in solving the old puzzle of PD.
Peptides encrypted in the human intestinal microbial-exoproteome as novel biomarkers and immunomodulatory compounds in the gastrointestinal tract
(Elsevier, 2019-01) Fernández-Tomé, Samuel; Montalban-Arqués, Ana; Díaz-Guerra, Alba; Galván-Román, JM; Marin, Alicia C; Mora-Gutiérrez, Irene; Ortega Moreno, Lorena; Santander, Cecilio; Sánchez, Borja; Chaparro, María; P. Gisbert, Javier; Bernardo, David
Peptides encrypted in the intestinal microbial-exoproteome mediate the host-microbiota crosstalk, which is disrupted in inflammatory bowel disease (IBD). Here, the MAHMI database was used for the identification of 20 novel intestinal bacterial peptides. Our results revealed that serum IgA levels directed towards the peptides, but not IgG, discriminated healthy controls from IBD patients. Indeed, they also differentiated patients with ulcerative colitis from Crohńs disease and, within them, patients with and without intestinal inflammation. All peptides were immunomodulatory as they changed the intestinal cytokine milieu following human lamina propria mononuclear cells culture (with/out LPS), revealing a Bifidobacterium longum subsp. longum peptide with the highest tolerogenic properties. Therefore, bacterial peptides encrypted in the human gut metaproteome may have utility as non-invasive biomarkers to aid on IBD diagnosis and monitoring. These peptides also display immunomodulatory effects on the intestinal mucosa revealing them as novel functional compounds for non-drug therapeutic strategies in IBD
Profiling of Human Circulating Dendritic Cells and Monocyte Subsets Discriminates Between Type and Mucosal Status in Patients With Inflammatory Bowel Disease
(2021) Ortega Moreno, Lorena; Fernández-Tomé, Samuel; Chaparro, María; Marin, Alicia C; Mora-Gutierrez, Irene; Santander, Cecilio; Baldan-Martin, Montse; Gisbert, Javier P.; Bernardo, David
[Background]: Intestinal dendritic cells (DC) and macrophages drive disease progression in patients with inflammatory bowel disease (IBD). We aimed to characterize the activation and homing profile of human circulating DC and monocyte subsets in healthy control patients (CP) and IBD patients.
Relationship between polymorphisms in the sulfotransferase SULT2A1 gene and dehydroepiandrosterone sulfate concentration in children
(Frontiers Media, 2013) García-Anguita, Alicia; Ortega Moreno, Lorena; Garcés, Carmen
Dehydroepiandrosterone sulfate (DHEA-S) is the most abundant circulating steroid hormone in humans, and has important physiological effects. A relationship has been suggested between variations of DHEA-S concentration and polymorphisms in the gene encoding sulfotransferase (SULT2A1), an enzyme that catalyzes the formation of DHEA-S from DHEA. We have investigated the relationship between the single nucleotide polymorphisms (SNPs) rs2637125 and rs182420 in the SULT2A1 gene and plasma DHEA-S concentration in children at two different ages. The sample population comprised 981 healthy 6-8-year-olds and 792 12-16-year-old children. In total, 12-16-year-old boys homozygous for the rare allele of rs182420 (CC) showed significantly lower DHEA-S concentration than TC boys, and both (TC and CC) had lower levels than TT boys. In all, 12-16 -year-old boy carriers of the rare allele for the rs2637125 polymorphism also showed lower levels of DHEA-S than GG carriers. No differences were observed in DHEA-S concentrations across genotypes in 6-8-year-old children. Our data show an age-related association of polymorphisms in the SULT2A1 gene with lower DHEA-S, suggesting that these polymorphisms may affect DHEA-S concentration in adults
Relationship of Adiponectin with Sex Hormone Levels in Adolescents
(Karger Publishers, 2013-02-15) Riestra, Pía; García-Anguita, Alicia; Ortega Moreno, Lorena; Garcés, Carmen
Background/Aims: Adiponectin is an adipose tissue-derived adipocytokine which, starting at puberty, is present in lower levels in males than in females. In adults, a relationship between adiponectin levels and sexual hormones has been suggested, but this association remains unclear in children. Our study aimed to analyze the relationship of adiponectin with dehydroepiandrosterone sulfate, testosterone, estradiol, and sex hormone-binding globulin (SHBG) in adolescents. Methods: The population-based sample included 785 healthy 12- to 16-year-old children. Testosterone, estradiol, and dehydroepiandrosterone sulfate levels were assessed by radioimmunoassay. SHBG was measured by immunoradiometric assay. Adiponectin concentrations were measured by ELISA. Results: Adiponectin levels were positively correlated with SHBG and negatively correlated with the free androgen index independently of body mass index (BMI) and fat mass. No significant correlations were observed between adiponectin and total testosterone or estradiol. Multiple linear regression analysis showed that, after adjustment for BMI, SHBG appears as the primary predictor of adiponectin levels in both sexes, accounting for 5.7% of the variation in adiponectin levels in boys and 7.5% in girls. Conclusion: Adiponectin is related to free androgen index and SHBG levels in adolescents after adjusting for BMI and fat mass, thus suggesting an association between adiponectin levels and androgen bioavailability that would explain the sex-based differences in adiponectin levels through life.
Relationship of Dehydroepiandrosterone Sulfate with Overweight and Insulin Sensitivity in 12–16-Year-old Spanish Children
(Thieme Gruppe, 2013) García-Anguita, Alicia; Ortega Moreno, Lorena; Garcés, Carmen
DHEA-S is the most abundant steroid hormone in human circulation. Although a relationship of DHEA-S with obesity-related diseases has been reported, the metabolic role of this hormone remains unclear, particularly in children. In our study, we have investigated the relationship of DHEA-S levels with anthropometric variables, insulin, HOMA, and free fatty acids in adolescents. The study sample included 812 healthy 12–16-year-old children (383 boys and 429 girls). Plasma DHEA-S was determined by RIA, insulin concentrations by IRMA, and free fatty acids by using a commercial kit. Insulin resistance was estimated using the HOMA index. No significant differences in plasma DHEA-S levels were found between sexes. DHEA-S levels in overweight children were significantly higher than in normal-weight children. DHEA-S levels were significantly correlated with weight and BMI after adjusting for age. Significant positive correlations between DHEA-S and free fatty acids levels were found after adjusting for age and BMI, particularly in boys, but not between DHEA-S levels and insulin or HOMA in either gender. DHEA-S levels in 12–16-year-old children are correlated with weight and BMI independently of age. We failed to find any association between DHEA-S and insulin levels, but we did find a significant correlation between DHEA-S and free fatty acids levels, suggesting that its association with free fatty acids may be related to the onset of the association of DHEA-S with insulin resistance
Serum adipokines as non‑invasive biomarkers in Crohn’s disease
(2020) Ortega Moreno, Lorena; Sanz García, Ancor; Fernández de la Fuente, Marina J; Arroyo Solera, Ricardo; Fernández-Tomé, Samuel; Marin, Alicia C; Mora-Gutierrez, Irene; Fernández, Paloma; Baldan-Martin, Montse; Chaparro, María; Gisbert, Javier P.; Bernardo, David
Adipose tissue secretes molecules that can promote activity in Crohn’s disease. We aimed to evaluate the role of serum adipokines as possible biomarkers in Crohn’s disease. Serum samples were obtained from 40 patients with endoscopically active or quiescent Crohn’s disease and 36 healthy controls. Serum leptin, ghrelin, resistin and adiponectin levels were analysed by Multiplex in a Luminex 200 system technology. Receiver Operating Characteristic curves were performed to evaluate the adipokines discriminatory capacity. A logistic regression adjusted by possible confounders (i.e. gender, age, BMI) was performed for those adipokines that showed an area under the curve> 0.7. No diferences were found in age, gender or BMI among groups. Distribution for serum resistin was diferent among the three groups of study, and only this adipokine showed an area under the curve of 0.75 comparing actives patients and healthy control groups. Resistin median concentration was selected as a cut-of for a logistic regression analysis; odds ratio along its 95% confdence interval adjusted by gender, age, and BMI yielded a value of 5.46 (1.34–22.14) comparing actives patients and healthy controls. High concentration of serum resistin is probably associated to activity, being this association independent of gender, age or BMI.
Serum Adiponectin and Glomerular Filtration Rate in Patients with Type 2 Diabetes
(PlosOne, 2015) Ortega Moreno, Lorena; Lamacchia, Olga; Copetti, Massimiliano; Salvemini, Lucia; De Bonis, Concetta; De Cosmo, Salvatore; Cignarelli, Mauro; Trischitta, Vincenzo; Menzaghi, Claudia
High serum adiponectin has been increased in several conditions of kidney disease. Only sparse and conflicting results have been reported in patients with type 2 diabetes (T2D), a subgroup of individuals who are at high risk for renal dysfunction. The aim of this study was to fill up this gap of knowledge by investigating such association in a large sample of Italian diabetic patients. The association between serum adiponectin levels and estimated glomerular filtration rate (eGFR by Chronic Kidney Disease-Epidemiology Collaboration CKD-EPI equation) was investigated in 1,243 patients with T2D from two cross-sectional Italian studies: 878 from San Giovanni Rotondo (SGR) and 365 from Foggia (FG). Serum adiponectin was inversely associated with eGFR in SGR [β (standard error, SE) for 1 standard deviation (SD) of adiponectin = -3.26 (0.64)] and in FG [β(SE)=-5.70(1.28)] sample, as well as in the two studies combined [β(SE)=-3.99(0.59)];(p<0.0001 for all). In this combined analysis, the association was still significant after adjusting for sex, smoking habits, body mass index (BMI), waist circumference, diabetes duration, glycated hemoglobin (HbA1c), albumin creatinine ratio (ACR) and anti-hyperglycemic, anti-hypertensive and anti-dyslipidemic treatments [β (SE)= -2.19 (0.59), p = 0.0001]. A stronger association between each SD adiponectin increment and low eGFR was observed among patients with micro-/macro-albuminuria, as compared to those with normo-albuminuria [adjusted β(SE)=-4.42(1.16) ml/min/ 1.73m2 vs. -1.50 (0.67) ml/min/1.73m2 , respectively; p for adiponectin-by-albuminuric status = 0.022]. For each adiponectin SD increment, the odds of having eGFR < 60 ml/min/1.73m2 increased by 41% (odds ratio, OR = 1.41; 95% confidence interval, CI 1.21–1.64) in SGR sample, 53% (OR = 1.53; 95% CI 1.21–1.94) in FG sample, and 44% (OR = 1.44; 95%CI 1.27–1.64) in the two studies considered together (p<0.0001 for all). In the combined sample, further adjustment for the above mentioned covariates did not change the observed association (OR = 1.36; 95%CI 1.16–1.60; p<0.0001). Our study, so far the largest addressing the relationship between serum adiponectin and GFR in T2D, strongly suggests that the paradoxical inverse association, previously reported in different clinical sets, is also observed in diabetic patients. Further studies are needed to unravel the biology underlying this counterintuitive relationship.
Serum Orotidine: A Novel Biomarker of Increased CVD Risk in T2D Discovered: Through Metabolomics Studies
(2022) Shah, Hetal; Ortega Moreno, Lorena; Morieri, Mario Luca; Tang, Yaling; Mendonca, Christine; Jobe, Jenny Marie; Thacker, Jonathan B.; Mitri, Joanna; Monti, Stefano; Niewczas, Monica; Pennathur, Subramaniam; Doria, Alessandro
OBJECTIVE To identify novel biomarkers of cardiovascular disease (CVD) risk in type 2 diabetes (T2D) via a hypothesis-free global metabolomics study, while taking into account renal function, an important confounder often overlooked in previous metabolomics studies of CVD. RESEARCH DESIGN AND METHODS We conducted a global serum metabolomics analysis using theMetabolon platform in a discovery set from the Joslin Kidney Study having a nested case-control design comprising 409 individuals with T2D. Logistic regression was applied to evaluate the association between incident CVD events and each of the 671 metabolites detected by the Metabolon platform, before and after adjustment for renal function and other CVD risk factors. Significant metabolites were followed up with absolute quantification assays in a validation set from the Joslin Heart Study including 599 individuals with T2D with and without clinical evidence of significant coronary heart disease (CHD). RESULTS In the discovery set, serum orotidine and 2-piperidinone were significantly associated with increased odds of incident CVD after adjustment for glomerular filtration rate (GFR) (odds ratio [OR] per SD increment 1.94 [95% CI 1.39–2.72], P 5 0.0001, and 1.62 [1.26–2.08], P 5 0.0001, respectively). Orotidine was also associated with increased odds of CHD in the validation set (OR 1.39 [1.11–1.75]), while 2-piperidinone did not replicate. Furthermore, orotidine, being inversely associated with GFR, mediated 60% of the effects of declining renal function on CVD risk. Addition of orotidine to established clinical predictors improved (P < 0.05) C statistics and discrimination indices for CVD risk (DAUC 0.053, rIDI 0.48, NRI 0.42) compared with the clinical predictors alone. CONCLUSIONS Through a robust metabolomics approach, with independent validation, we have discovered serum orotidine as a novel biomarker of increased odds of CVD in T2D, independent of renal function. Additionally, orotidine may be a biological mediator of the increased CVD risk associated with poor kidney function and may help improve CVD risk prediction in T2D.