Burrell, M.A. (María Ángela)
- Publications
- item.page.relationships.isContributorAdvisorOfPublication
- item.page.relationships.isContributorOfPublication
19 results
Search Results
Now showing 1 - 10 of 19
- Increased expression levels of netrin-1 in visceral adipose tissue during obesity favour colon cancer cell migration(2023) Neira, G. (Gabriela); Valenti, V. (Víctor); Ferro, A. (Alberto); Baixauli-Fons, J. (Jorge); Ramirez, B. (Beatriz); Catalan, V. (Victoria); Mentxaka, A. (Amaia); Becerril, S. (Sara); Frühbeck, G. (Gema); Burrell, M.A. (María Ángela); Moncada, R. (Rafael); Silva, C. (Camilo); Gomez-Ambrosi, J. (Javier); Rodriguez, A. (Amaia); Claro, V. (Vasco)Simple Summary Netrin-1 (NTN-1) regulates obesity-associated low-grade inflammation, being also involved in the control of cell migration and proliferation. We aim to study whether excess visceral adipose tissue in patients with obesity and colon cancer is associated with increased NTN1 and the expression levels of its main receptors, promoting an inflammatory microenvironment that favours colon cancer development. Increased expression levels of NTN1 and its receptor NEO1 in the visceral adipose tissue from patients with obesity and colon cancer together with elevated DCC and UNC5B mRNA levels in patients with colon cancer were found. Moreover, the treatment of colorectal cancer cells with NTN-1 and with the adipocyte-derived secretome obtained from patients with obesity increased the migration of colorectal cancer cells. These results suggest that NTN-1 plays an important role in obesity-associated colon cancer development. Netrin (NTN)-1, an extracellular matrix protein with a crucial role in inflammation, is dysregulated during obesity (OB) and influences colon cancer (CC) progression. To decipher the mechanisms underlying CC development during obesity, we examined the expression of NTN1 and its receptors in the visceral adipose tissue (VAT) of 74 (25 normal weight (NW)) (16 with CC) and 49 patients with OB (12 with CC). We also evaluated the effect of caloric restriction (CR) on the gene expression levels of Ntn1 and its receptors in the colon from a rat model fed a normal diet. The impact of adipocyte-conditioned media (ACM) from patients with OB and NTN-1 was assessed on the expression levels of neogenin 1(NEO1), deleted in colorectal carcinomas (DCC) and uncoordinated-5 homolog B (UNC5B) in Caco-2 and HT-29 human colorectal cell lines, as well as on Caco-2 cell migration. Increased NTN1 and NEO1 mRNA levels in VAT were due to OB (p < 0.05) and CC (p < 0.001). In addition, an upregulation in the expression levels of DCC and UNC5B in patients with CC (p < 0.01 and p < 0.05, respectively) was observed. Decreased (p < 0.01) Ntn1 levels in the colon from rats submitted to CR were found. In vitro experiments showed that ACM increased DCC (p < 0.05) and NEO1 (p < 0.01) mRNA levels in HT-29 and Caco-2 cell lines, respectively, while UNC5B decreased (p < 0.01) in HT-29. The treatment with NTN-1 increased (p < 0.05) NEO1 mRNA levels in HT-29 cells and DCC (p < 0.05) in both cell lines. Finally, we revealed a potent migratory effect of ACM and NTN-1 on Caco-2 cells. Collectively, these findings point to increased NTN-1 during OB and CC fuelling cancer progression and exerting a strong migratory effect on colon cancer cells.
- Microspore embryogenesis induction by mannitol and TSA results in a complex regulation of epigenetic dynamics and gene expression in bread wheat(2023) Burrell, M.A. (María Ángela); Valero-Rubira, I. (Isabel); Vallés, M.P. (María Pilar); Castillo, A.M. (Ana María)Reprogramming of microspores development towards embryogenesis mediated by stress treatment constitutes the basis of doubled haploid production. Recently, compounds that alter histone post-translational modifications (PTMs) have been reported to enhance microspore embryogenesis (ME), by altering histones acetylation or methylation. However, epigenetic mechanisms underlying ME induction efficiency are poorly understood. In this study, the epigenetic dynamics and the expression of genes associated with histone PTMs and ME induction were studied in two bread wheat cultivars with different ME response. Microspores isolated at 0, 3 and 5 days, treated with 0.7M mannitol (MAN) and 0.7M mannitol plus 0.4 mu M trichostatin A (TSA), which induced ME more efficiently, were analyzed. An additional control of gametophytic development was included. Microspores epigenetic state at the onset of ME induction was distinctive between cultivars by the ratio of H3 variants and their acetylated forms, the localization and percentage of labeled microspores with H3K9ac, H4K5ac, H4K16ac, H3K9me2 and H3K27me3, and the expression of genes related to pollen development. These results indicated that microspores of the high responding cultivar could be at a less advanced stage in pollen development. MAN and TSA resulted in a hyperacetylation of H3.2, with a greater effect of TSA. Histone PTMs were differentially affected by both treatments, with acetylation being most concerned. The effect of TSA was observed in the H4K5ac localization pattern at 3dT in the mid-low responding cultivar. Three gene networks linked to ME response were identified. TaHDT1, TaHAG2, TaYAO, TaNFD6-A, TabZIPF1 and TaAGO802-B, associated with pollen development, were down-regulated. TaHDA15, TaHAG3, TaHAM, TaYUC11D, Ta-2B-LBD16 TaMS1 and TaDRM3 constituted a network implicated in morphological changes by auxin signaling and cell wall modification up-regulated at 3dT. The last network included TaHDA18, TaHAC1, TaHAC4, TaABI5, TaATG18fD, TaSDG1a-7A and was related to ABA and ethylene hormone signaling pathways, DNA methylation and autophagy processes, reaching the highest expression at 5dT. The results indicated that TSA mainly modified the regulation of genes related to pollen and auxin signaling. This study represents a breakthrough in identifying the epigenetic dynamics and the molecular mechanisms governing ME induction efficiency, with relevance to recalcitrant wheat genotypes and other crops.
- Intracellular killing of Brucella melitensis in human macrophages with microspheres-encapsulated gentamicin(Oxford University Press, 2006-06-26) Lecaroz, M.C. (María Concepción); Blanco-Prieto, M.J. (María José); Gamazo, C. (Carlos); Burrell, M.A. (María Ángela)Objectives: Treatment of human brucellosis demands antibiotic targeting into the mononuclearphagocytic system. The aim of this work was to prepare and characterize particulate carriers containing gentamicin and to study their interactions with phagocytic cells and bactericidal activity against intracellular Brucella melitensis. Methods: Different poly(lactide-co-glycolide) (PLGA)polymers with free carboxylic end-group wereusedto formulate micro- and nanoparticles containing gentamicin, by a water-oil-water solvent-evaporation technique. PLGA 502H and 75:25H microparticles were selected because they showed the highest gentamicin loadings as well as good physico-chemical properties and sustained release in vitro. Results: Gentamicin-containing microspheres of both polymers were successfully phagocytosed by infected THP-1 human monocytes, and immunocytochemistry studies revealed that the antibiotic reached Brucella-specific compartments. A dose of 30 mg of encapsulated gentamicin was able to reduce intracellular Brucella infection by 2.2 log. Conclusions: Altogether, these results suggest that 502H and 75:25H microspheres are suitable carriers for gentamicin targeting inside human macrophages and thus for brucellosis treatment.
- Effect of guanylin peptides on pancreas steatosis and function in experimental diet-induced obesity and after bariatric surgery(2023) Valenti, V. (Víctor); Otero, A. (Aarón); Catalan, V. (Victoria); Álvarez-Cienfuegos, J. (Javier); Becerril, S. (Sara); Frühbeck, G. (Gema); Burrell, M.A. (María Ángela); Martín-Rodríguez, M. (Marina); Gomez-Ambrosi, J. (Javier); Rodriguez, A. (Amaia); Moncada-Durruti, R. (Rafael)Introduction: Obesity contributes to ectopic fat deposition in non-adipose organs, including the pancreas. Pancreas steatosis associates with inflammation and beta-cell dysfunction, contributing to the onset of insulin resistance and type 2 diabetes. An improvement of pancreatic steatosis and indices of insulin resistance is observed following bariatric surgery, but the underlying mechanisms remain unknown. We sought to analyze whether guanylin (GUCA2A) and uroguanylin (GUCA2B), two gut hormones involved in the regulation of satiety, food preference and adiposity, are involved in the amelioration of pancreas fat accumulation after bariatric surgery. Methods: Pancreas steatosis, inflammation, islet number and area were measured in male Wistar rats with diet-induced obesity (n=125) subjected to surgical (sham operation and sleeve gastrectomy) or dietary (pair-fed to the amount of food eaten by gastrectomized animals) interventions. The tissue distribution of guanylate cyclase C (GUCY2C) and the expression of the guanylin system were evaluated in rat pancreata by real-time PCR, Western-blot and immunohistochemistry. The effect of guanylin and uroguanylin on factors involved in insulin secretion and lipogenesis was determined in vitro in RIN-m5F beta-cells exposed to lipotoxic conditions. Results: Sleeve gastrectomy reduced pancreas steatosis and inflammation and improved insulin sensitivity and synthesis. An upregulation of GUCA2A and GUCY2C, but not GUCA2B, was observed in pancreata from rats with dietinduced obesity one month after sleeve gastrectomy. Interestingly, both guanylin and uroguanylin diminished the lipotoxicity in palmitate-treated RIN-m5F beta-cells, evidenced by lower steatosis and downregulated lipogenic factors Srebf1, Mogat2 and Dgat1. Both guanylin peptides reduced insulin synthesis (Ins1 and Ins2) and release from RIN-m5F beta-cells, but only guanylin upregulated Wnt4, a factor that controls beta-cell proliferation and function. Discussion: Together, sleeve gastrectomy reduced pancreatic steatosis and improved beta-cell function. Several mechanisms, including the modulation of inflammation and lipogenesis as well as the upregulation of GUCA2A in the pancreas, might explain this beneficial effect of bariatric surgery.
- Expression of leptin and adiponectin in the rat oviduct(2007-06-15T08:33:02Z) Tena-Sempere, M. (Manuel); Burrell, M.A. (María Ángela); Archanco, M. (M.)SUMMARY In mammals, the oviduct is an important source of factors that play key roles in reproductive and developmental events. The major components of oviduct fluid are oviductspecific glycoproteins, but other proteins are synthesized and secreted by the oviduct epithelium. Leptin and adiponectin are two hormones originally identified in adipocytes that play a critical role not only in the control of energy balance and metabolism but also in diverse functions such as reproduction. This study investigates the presence and distribution of leptin and adiponectin in the rat oviduct through a combination of immunohistochemistry and reverse transcription–polymerase chain reaction techniques. Using both techniques, it has been detected that the oviduct of cycling rats expresses leptin and adiponectin. Immunoreactivity for both adipokines appears in the apical region of the secretory epithelial cells, only in the isthmus and ampulla. The immunostain is stronger in the isthmus and changes throughout the estrous cycle in the ampulla, increasing from proestrous to estrous. The results presented here are a further contribution to the identification of leptin and adiponectin produced and secreted by the oviduct epithelium, which must be taken into account for a better understanding of the reproductive events that take place in this organ.
- The diffuse endocrine system: from embryogenesis to carcinogenesis(Elsevier, 2003) Sesma, M.P. (María Pilar); Villaro, A.C. (Ana Cristina); Burrell, M.A. (María Ángela); Montuenga-Badia, L.M. (Luis M.); Guembe, L. (L.); Bodegas-Frías, E. (Elena); Calvo-González, A. (Alfonso); Sola, J.J. (Jesús Javier)In the present review we will summarise the current knowledge about the cells comprising the Diffuse Endocrine System (DES) in mammalian organs. We will describe the morphological, histochemical and functional traits of these cells in three major systems gastrointestinal, respiratory and prostatic. We will also focus on some aspects of their ontogeny and differentiation, as well as to their relevance in carcinogenesis, especially in neuroendocrine tumors. The first chapter describes the characteristics of DES cells and some of their specific biological and biochemical traits. The second chapter deals with DES in the gastrointestinal organs, with special reference to the new data on the differentiation mechanisms that leads to the appearance of endocrine cells from an undifferentiated stem cell. The third chapter is devoted to DES of the respiratory system and some aspects of its biological role, both, during development and adulthood. Neuroendocrine hyperplasia and neuroendocrine lung tumors are also addressed. Finally, the last chapter deals with the prostatic DES, discussing its probable functional role and its relevance in hormone-resistant prostatic carcinomas.
- Sleeve gastrectomy induces weight loss in diet-induced obese rats even if high-fat feeding is continued(Rapid Communications, 2010-09-12) Valenti, V. (Víctor); Ramirez, B. (Beatriz); Fernández-González, S. (Secundino); Becerril, S. (Sara); Burrell, M.A. (María Ángela); Rodriguez, A. (Amaia)Abstract BACKGROUND: Sleeve gastrectomy (SG) has been used for the surgical treatment of morbid obesity as a first or definitive procedure with satisfactory results. The objective of this study in rats was to establish the effects of SG on weight loss depending on the post-surgical type of diet followed. METHODS: Thirty male Wistar rats were fed ad libitum during 3 months on a high-fat diet (HFD) to induce obesity. After this first phase, rats were subdivided in three groups of ten rats each and underwent a sham intervention, an SG, or no surgery but were pair-fed to the amount of food eaten by the animals of the SG group. At this time point, half of the animals in each group continued to be fed on the HFD, while the other half was switched to a normal chow diet (ND). Thus, the following subgroups were established: sham-ND, sleeve-ND, pair-fed-ND as well as sham-HFD, sleeve-HFD, and pair-fed-HFD. Body weight and food intake were recorded daily for 4 weeks. The feed efficiency rate (FER) was determined from weekly weight gains and caloric consumption during this period. RESULTS: Statistically significant (P < 0.05) differences in body weight were observed between the six experimental groups after 4 weeks of the interventions with rats in the sleeve-ND group experimenting the highest weight loss (-78.2 ± 10.3 g) and animals in the pair-fed-HFD group exhibiting the lowest weight reduction (-4.0 ± 0.1 g). Interestingly, the FER value of rats that underwent the SG and continued to be fed on a HFD was significantly (P < 0.05) lower than that of sham operated and pair-fed animals on the same diet. CONCLUSION: The positive effects of SG on weight reduction are observed in obese rats submitted to the intervention and subsequently following an ND or even an HFD.
- Uroguanylin prevents hepatic steatosis, mitochondrial dysfunction and fibrosis in obesity-associated NAFLD(Elsevier, 2023) Valenti, V. (Víctor); Colina, I. (Inmaculada); Catalan, V. (Victoria); Becerril, S. (Sara); Frühbeck, G. (Gema); Fernández-Sáez, E.M. (Eva M.); Losarcos, M. (Maite); Burrell, M.A. (María Ángela); Martín, M. (Mariana); Moncada, R. (Rafael); Mugueta, C. (Carmen); Silva, C. (Camilo); Gomez-Ambrosi, J. (Javier); Rodriguez, A. (Amaia); Escalada, J. (Javier)Background: The biological mediators supporting the resolution of liver steatosis, inflammation and fibrosis after bariatric surgery in patients with obesity and NAFLD remain unclear. We sought to analyze whether uroguanylin and guanylin, two gut hormones involved in the regulation of satiety, food preference and adiposity, are involved in the amelioration of obesity-associated NAFLD after bariatric surgery. Methods: Proguanylin (GUCA2A) and prouroguanylin (GUCA2B) were measured in 214 participants undergoing bariatric surgery with biopsy-proven NAFLD diagnosis. Pathways involved in lipid metabolism, mitochondrial network and fibrogenesis were evaluated in liver biopsies (n = 137). The effect of guanylin and uroguanylin on these metabolic functions was assessed in HepG2 hepatocytes and LX-2 hepatic stellate cells (HSC) under lipotoxic and profibrogenic conditions. Results: Plasma and hepatic expression of GUCA2B were decreased in obesity-associated NAFLD. Both GUCA2A and GUCA2B levels were increased after sleeve gastrectomy and Roux-en-Y gastric bypass in parallel to the improved liver function. The liver of patients with type 2 diabetes showed impaired mitochondrial β-oxidation, biogenesis, dynamics as well as increased fibrosis. Uroguanylin diminished the lipotoxicity in palmitate-treated HepG2 hepatocytes, evidenced by decresased steatosis and lipogenic factors, as well as increased mitochondrial network expression, AMPK-induced β-oxidation and oxygen consumption rate. Additionally, uroguanylin, but not guanylin, reversed HSC myofibroblast transdifferentiation as well as fibrogenesis after TGF-β1 stimulation. Conclusions: Uroguanylin constitutes a protective factor against lipotoxicity, mitochondrial dysfunction and fibrosis. Increased GUCA2B levels might contribute to improve liver injury in patients with obesity-associated NAFLD after bariatric surgery.
- Osteopontin deletion prevents the development of obesity and hepatic steatosis via impaired adipose tissue matrix remodeling and reduced inflammation and fibrosis in adipose tissue and liver in mice(2014) Ramirez, B. (Beatriz); Catalan, V. (Victoria); Becerril, S. (Sara); Lancha, A. (Andoni); Frühbeck, G. (Gema); Burrell, M.A. (María Ángela); Gomez-Ambrosi, J. (Javier); Salvador, J. (Javier); Rodriguez, A. (Amaia); Sainz, N. (Neira)Osteopontin (OPN) is a multifunctional extracellular matrix (ECM) protein involved in multiple physiological processes. OPN expression is dramatically increased in visceral adipose tissue in obesity and the lack of OPN protects against the development of insulin resistance and inflammation in mice. We sought to unravel the potential mechanisms involved in the beneficial effects of the absence of OPN. We analyzed the effect of the lack of OPN in the development of obesity and hepatic steatosis induced by a high-fat diet (HFD) using OPN-KO mice. OPN expression was upregulated in epididymal white adipose tissue (EWAT) and liver in wild type (WT) mice with HFD. OPN-KO mice had higher insulin sensitivity, lower body weight and fat mass with reduced adipose tissue ECM remodeling and reduced adipocyte size than WT mice under a HFD. Reduced MMP2 and MMP9 activity was involved in the decreased ECM remodeling. Crown-like structure number in EWAT as well as F4/80-positive cells and Emr1 expression in EWAT and liver increased with HFD, while OPN-deficiency blunted the increase. Moreover, our data show for the first time that OPN-KO under a HFD mice display reduced fibrosis in adipose tissue and liver, as well as reduced oxidative stress in adipose tissue. Gene expression of collagens Col1a1, Col6a1 and Col6a3 in EWAT and liver, as well as the profibrotic cytokine Tgfb1 in EWAT were increased with HFD, while OPN-deficiency prevented this increase. OPN deficiency prevented hepatic steatosis via reduction in the expression of molecules involved in the onset of fat accumulation such as Pparg, Srebf1, Fasn, Mogat1, Dgat2 and Cidec. Furthermore, OPN-KO mice exhibited higher body temperature and improved BAT function. The present data reveal novel mechanisms of OPN in the development of obesity, pointing out the inhibition of OPN as a promising target for the treatment of obesity and fatty liver.
- PRDM16: The intercovertible adipo-myocyte switch(Elsevier, 2009-04) Sesma, M.P. (María Pilar); Frühbeck, G. (Gema); Burrell, M.A. (María Ángela)Both brown and white adipocytes were previously considered to be derived from the same precursor cell, despite being histologically and functionally different. However, a recent study shows that overexpression of the transcriptional regulator positive regulatory domain containing 16 (PRDM16) determines the development of brown adipocytes from a progenitor that expresses myoblast markers. Surprisingly, loss of PRDM16 from these precursors does not lead to white adipocyte differentiation. Thus, PRDM16 controls a bidirectional cell fate switch between skeletal myoblasts and brown adipocytes