Differential gene expression profile in omental adipose tissue in women with polycystic ovary syndrome

10 pages, 2 figures, 5 tables.CONTEXT: The polycystic ovary syndrome (PCOS) is frequently associated with visceral obesity, suggesting that omental adipose tissue might play an important role in the pathogenesis of the syndrome. OBJECTIVE: The objective was to study the expression profiles of omental fat biopsy samples obtained from morbidly obese women with or without PCOS at the time of bariatric surgery. DESIGN: This was a case-control study. SETTINGS: We conducted the study in an academic hospital. PATIENTS: Eight PCOS patients and seven nonhyperandrogenic women submitted to bariatric surgery because of morbid obesity. INTERVENTIONS: Biopsy samples of omental fat were obtained during bariatric surgery. MAIN OUTCOME MEASURE: The main outcome measure was high-density oligonucleotide arrays. RESULTS: After statistical analysis, we identified changes in the expression patterns of 63 genes between PCOS and control samples. Gene classification was assessed through data mining of Gene Ontology annotations and cluster analysis of dysregulated genes between both groups. These methods highlighted abnormal expression of genes encoding certain components of several biological pathways related to insulin signaling and Wnt signaling, oxidative stress, inflammation, immune function, and lipid metabolism, as well as other genes previously related to PCOS or to the metabolic syndrome. CONCLUSION: The differences in the gene expression profiles in visceral adipose tissue of PCOS patients compared with nonhyperandrogenic women involve multiple genes related to several biological pathways, suggesting that the involvement of abdominal obesity in the pathogenesis of PCOS is more ample than previously thought and is not restricted to the induction of insulin resistance.This work was supported by PI020578, PI020741, PI050341, PI050551, RCMN C03/08, and RGDM 03/212 from Fondo de Investigación Sanitaria, Instituto de Salud Carlos III, and Grants 08.6/0021/2003 and GR/SAL/0137/2004 from the Consejería de Educación y Cultura, Comunidad de Madrid, Spain.Peer reviewe

Clinical nutrition as part of the treatment pathway of pancreatic cancer patients: an expert consensus

Consensus; Nutritional screening; Pancreatic cancerConsenso; Cribado nutricional; Cáncer de páncreasConsens; Cribratge nutricional; Càncer de pàncreesPurpose Malnutrition is a common problem among pancreatic cancer (PC) patients that negatively impacts on their quality of life (QoL) and clinical outcomes. The main objective of this consensus is to address the role of Medical Nutrition Therapy (MNT) into the comprehensive therapeutic management of PC patients. Methods A Spanish multidisciplinary group of specialists from the areas of Medical Oncology; Radiation Oncology; Endocrinology and Nutrition; and General Surgery agreed to assess the role of MNT as part of the best therapeutic management of PC patients. Results The panel established different recommendations focused on nutritional screening and nutritional screening tools, MNT strategies according to PC status, and MNT in palliative treatment. Conclusions There is an unmet need to integrate nutritional therapy as a crucial part of the multimodal care process in PC patients. Health authorities, health care professionals, cancer patients, and their families should be aware of the relevance of nutritional status and MNT on clinical outcomes and QoL of PC patients.Open Access funding provided thanks to the CRUE-CSIC agreement with Springer Nature.

Proteomic analysis of human omental adipose tissue in the polycystic ovary syndrome using two-dimensional difference gel electrophoresis and mass

BACKGROUND: Our aim was to study the protein expression profiles of omental adipose tissue biopsies obtained from morbidly obese women with or without polycystic ovary syndrome (PCOS) at the time of bariatric surgery to evaluate the possible involvement of visceral adiposity in the development of PCOS. METHODS: Ten PCOS patients and nine control samples were included. We used two-dimensional difference gel electrophoresis (2D-DIGE) followed by in-gel digestion, and mass spectrometry (MS) of selected protein spots. RESULTS: The 2D-DIGE technology allowed the analysis of 1840 protein spots in the comparative study of control and patient proteomes, revealing 15 statistically significant spot changes (>2-fold, P < 0.05). Unambiguous protein identification was achieved for 9 of these 15 spots by MS. This preliminary study revealed differences in expression of proteins that may be involved in lipid and glucose metabolism, oxidative stress processes and adipocyte differentiation; they include proapolipoprotein Apo-A1, annexin V, glutathione S-transferase M3 (GSTM3), triosephosphate isomerase, peroxiredoxin 2 isoform a, actin and adipocyte plasma membrane-associated protein. The most relevant finding was an increase of GSTM3 in the omental fat of PCOS patients confirming previous studies conducted by our group. CONCLUSIONS: Proteomic analysis of omental fat reveals differential expression of several proteins in PCOS patients and non-hyperandrogenic women presenting with morbid obesity. The application of this novel methodology adds further evidence to support the role of visceral adiposity in the pathogenesis of PCOS

Impacto de la cirugía bariátrica en la microbiota intestinal y el metaboloma fecal

Resumen del trabajo presentado a la 14ª Reunión de la Red Española de Bacterias Lácticas (RedBAl), celebrada de forma telemática del 8 al 10 de Septiembre de 2021.Introducción: El tratamiento de la obesidad severa mediante cirugía bariátrica presenta la mejor relación efectividad/coste, siendo el sleeve gástrico (SG) y el bypass gástrico (BPG) las técnicas laparoscópicas más utilizadas. El BPG está recomendado en pacientes con mayor exceso de peso (IMC>50). Aunque se han descrito alteraciones en la microbiota intestinal (MI) en relación con la obesidad, existen pocos estudios en obesidad severa en los que se haya caracterizado este ecosistema y el metaboloma fecal. Objetivos: Evaluar el impacto de la dieta pre-operatoria y la técnica de cirugía bariátrica sobre la MI y el metaboloma fecal en obesidad severa. Sujetos y métodos: Se incluyeron 40 pacientes de cirugía bariátrica (14 SG y 26 BPG), se recogió información clínica de interés, así como muestras de heces a cuatro tiempos: 1)-basal, 2)-tras dieta preoperatoria, 3)-al mes y 4)- a los tres meses de la cirugía. Se determinó la composición de la MI mediante secuenciación del gen ARNr 16S y la concentración fecal de varios metabolitos (ácidos grasos de cadena corta-AGCC, aminoácidos y aminas biógenas-AB) mediante cromatografía de gases y líquida. Resultados: Se han detectado diferencias significativas en la composición de la MI de la muestra basal de los pacientes de BPG y de SG y cambios estadísticamente significativos en la composición de la MI y en el metaboloma fecal entre las cuatro muestras, existiendo un mayor impacto en el BPG. En el caso del patrón fecal de AGCC, ambas cirugías disminuyeron la concentración de los AGCC mayoritarios, aunque no hubo diferencias significativas entre ambas. La concentración fecal de aminoácidos transcurridos tres meses desde la operación fue en general inferior en el grupo de pacientes sometidos a BPG, mientras que la concentración de AB fue superior en comparación con los individuos operados mediante SG. Conclusiones: Los pacientes con obesidad severa e IMC>50 tienen una MI diferente, con mayor abundancia de Firmicutes. La cirugía bariátrica y la dieta preoperatoria asociada modifican la composición de la MI y el perfil de metabolitos fecales, siendo estos cambios más profundos cuando se utiliza la técnica de BPG, probablemente por la alteración anatómica del tránsito intestinal

A body weight loss- and health-promoting gut microbiota is established after bariatric surgery in individuals with severe obesity

Obesity has reached an epidemic level worldwide, and bariatric surgery (BS) has been proven to be the most efficient therapy to reduce severe obesity-related comorbidities. Given that the gut microbiota plays a causal role in obesity development and that surgery may alter the gut environment, investigating the impact of BS on the microbiota in the context of severe obesity is important. Although, alterations at the level of total gut bacteria, total gene content and total metabolite content have started to be disentangled, a clear deficit exists regarding the analysis of the active fraction of the microbiota, which is the fraction that is most reactive to the BS. Here, active gut microbiota and associated metabolic functions were evaluated using shotgun proteomics and metabolomics in 40 severely obese volunteers. Samples from each volunteer were obtained under basal conditions, after a short high protein and calorie-restricted diet, and 1 and 3 months after BS, including laparoscopic surgery through Roux-en-Y Gastric Bypass or Sleeve Gastrectomy. The results revealed for the first time the most active microbes and metabolic flux distribution pre- and post-surgery and deciphered main differences in the way sugars and short-fatty acids are metabolized, demonstrating that less energy-generating and anaerobic metabolism and detoxification mechanisms are promoted post-surgery. A comparison with non-obese proteome data further signified different ways to metabolize sugars and produce short chain fatty acids and deficiencies in proteins involved in iron transport and metabolism in severely obese individuals compared to lean individuals.This work was funded by grants SAF2015-65878-R, BIO2017-85522-R, PID2019-105969GB-I00 and RTI2018-095166-B-I00 from the Ministry of Science, Innovation and Universities, by the Ministry of Science and Innovation, by the Instituto de Salud Carlos III (projects PIE14/00045 and AC17/00022), Fundación Agencia Española contra el Cáncer and Instituto de Salud Carlos III(projects ERA NET TRANSCAN-2 AC17/00022 and AECC 2017-1485), Generalitat Valenciana (project Prometeo/2018/A/133) and co-financed by the European Regional Development Fund (ERDF). The proteomic analysis was performed in the Proteomics Facility of The Spanish National Center for Biotechnology (CNB-CSIC) that belongs to ProteoRed, PRB3-ISCIII, supported by grant PT17/0019.Peer reviewe

CIBERER : Spanish national network for research on rare diseases: A highly productive collaborative initiative

Altres ajuts: Instituto de Salud Carlos III (ISCIII); Ministerio de Ciencia e Innovación.CIBER (Center for Biomedical Network Research; Centro de Investigación Biomédica En Red) is a public national consortium created in 2006 under the umbrella of the Spanish National Institute of Health Carlos III (ISCIII). This innovative research structure comprises 11 different specific areas dedicated to the main public health priorities in the National Health System. CIBERER, the thematic area of CIBER focused on rare diseases (RDs) currently consists of 75 research groups belonging to universities, research centers, and hospitals of the entire country. CIBERER's mission is to be a center prioritizing and favoring collaboration and cooperation between biomedical and clinical research groups, with special emphasis on the aspects of genetic, molecular, biochemical, and cellular research of RDs. This research is the basis for providing new tools for the diagnosis and therapy of low-prevalence diseases, in line with the International Rare Diseases Research Consortium (IRDiRC) objectives, thus favoring translational research between the scientific environment of the laboratory and the clinical setting of health centers. In this article, we intend to review CIBERER's 15-year journey and summarize the main results obtained in terms of internationalization, scientific production, contributions toward the discovery of new therapies and novel genes associated to diseases, cooperation with patients' associations and many other topics related to RD research

Treatment of hypothyroidism with combinations of levothyroxine plus liothyronine

9 pages, 3 figures, 4 tables.-- Review.CONTEXT: Combined infusion of levothyroxine plus liothyronine, as opposed to levothyroxine alone, is the only way of restoring the concentrations of circulating TSH, T4, and T3 as well as those of both T4 and T3 in all tissues of thyroidectomized rats. Considering the substantial differences in thyroid hormone secretion, transport, and metabolism between rats and humans, whether or not combined levothyroxine plus liothyronine replacement therapy has advantages over treatment with levothyroxine alone in hypothyroid patients is still questioned. EVIDENCE ACQUISITION: We conducted a systematic review of all the published controlled studies comparing treatment with levothyroxine alone with combinations of levothyroxine plus liothyronine in hypothyroid patients, identified through the Entrez-PubMed search engine. EVIDENCE SYNTHESIS: Nine controlled clinical trials were identified that compared treatment with levothyroxine alone and treatment with combinations of levothyroxine plus liothyronine and included a sufficient number of adult hypothyroid patients to yield meaningful results. In only one study did the combined therapy appear to have beneficial effects on the mood, quality of life, and psychometric performance of the patients over levothyroxine alone. These results have not been confirmed by later studies using either T3 substitution protocols or approaches with fixed combinations of levothyroxine plus liothyronine, including those based on the physiological proportion in which T3 and T4 are secreted by the human thyroid. However, in some of these studies the patients preferred levothyroxine plus liothyronine combinations, for reasons not explained by changes in the psychological and psychometric tests employed. Yet patients' preference should be balanced against the possibility of adverse events resulting from the addition of liothyronine to levothyroxine, even in the small doses used in these studies. CONCLUSIONS: Until clear advantages of levothyroxine plus liothyronine are demonstrated, the administration of levothyroxine alone should remain the treatment of choice for replacement therapy of hypothyroidism.This work was supported by Grant 01/0430/01 from the Consejería de Educación, Comunidad de Madrid (to J.I.B.-C.) and by grants from the Fondo de Investigación Sanitaria, Instituto de Salud Carlos III (01/ F072 to J.I.B.-C.; and RCMN 03/08 and PI 03/1417 to G.M.d.E.).Peer reviewe

Treatment of hypothyroidism with levothyroxine or a combination of levothyroxine plus L-triiodothyronine

At present, the drug of choice for the treatment of hypothyroidism is levothyroxine sodium, even though the thyroid gland secretes both thyroxine and 30,3,5-triiodothyronine; the latter is the more active of the two at the cellular level because of its higher affinity for the nuclear thyroid hormone receptors. To date, combined levothyroxine plus liothyronine treatment for hypothyroidism has been evaluated in 15 clinical trials in humans. In two studies, combined therapy seemed to have beneficial effects on mood, quality of life, and psychometric performance of patients, compared with levothyroxine alone; in some of these studies, the patients preferred levothyroxine plus liothyronine combinations. This preference should be balanced against the possibility of adverse events resulting from the addition of liothyronine to levothyroxine. Until clear advantages of levothyroxine plus liothyronine are refdemonstrated, the administration of levothyroxine alone should remain the treatment of choice for replacement therapy of hypothyroidism.Peer Reviewe

Improved resolution of the human adipose tissue proteome at alkaline and wide range pH by the addition of hydroxyethyl disulfide

Polycystic ovary syndrome is a very common disease affecting 6.5% of women. It is frequently associated with obesity with the link between the two disorders being insulin resistance. From morbidly obese women submitted to surgical treatment of obesity, we obtain intra-abdominal adipose tissue samples in order to compare protein patterns between women with and without polycystic ovary syndrome by two-dimensional gel electrophoresis (2-DE) analysis. Adipose tissue is a complex material extremely rich in lipids. To improve protein solubilization a lysis buffer containing 8.4 m urea, 2.4 m thiourea, 5% 3-((3-cholamidoproyl)dimethyl-amino)-1-propanesulfonate and 50 mm dithiothreitol was used and samples were centrifuged to remove fat. Hydroxyethyl disulfide was added to increase resolution in the alkaline region (Olsson, I., Larsson, K., Palmgren, R., Bjellqvist, B., Proteomics 2002, 2, 1630-1632) and it also improved resolution in a wide pH range (3-10). Our work shows for the first time 2-DE maps of human adipose tissue and identifies some of the proteins by mass spectrometry. This information will aid studies on metabolic diseases such as polycystic ovary syndrome, obesity, hypertension and type 2 diabetes