Nuestros investigadores

María del Carmen Mugueta Uriaque

Laboratorio de Bioquímica
Clínica Universidad de Navarra. Clínica Universidad de Navarra
Bioquímica y Genética
Facultad de Ciencias. Universidad de Navarra
Facultad de Medicina. Universidad de Navarra
Líneas de investigación
Calidad Laboratorio Clínico, Enfermedad Alzheimer, Obesidad, Proteínas plasmáticas

Publicaciones científicas más recientes (desde 2010)

Autores: Anon-Hidalgo, J.; Catalán, V; Rodríguez, Amaia; et al.
ISSN 2077-0383  Vol. 8  Nº 6  2019  págs. 878
Growth differentiation factor 11 (GDF11) is a member of the transforming growth factor (TGF)-beta superfamily which declines with age and has been proposed as an anti-aging factor with regenerative effects in skeletal muscle in mice. However, recent data in humans and mice are conflicting, casting doubts about its true functional actions. The aim of the present study was to analyze the potential involvement of GFD11 in energy homeostasis in particular in relation with thyroid hormones. Serum concentrations of GDF11 were measured by enzyme-linked immunosorbent assay (ELISA) in 287 subjects. A highly significant positive correlation was found between GDF11 and thyroid-stimulating hormone (TSH) concentrations (r = 0.40, p < 0.001). Neither resting energy expenditure (REE) nor REE per unit of fat-free mass (REE/FFM) were significantly correlated (p > 0.05 for both) with GDF11 levels. In a multiple linear regression analysis, the model that best predicted logGDF11 included logTSH, leptin, body mass index (BMI), age, and C-reactive protein (logCRP). This model explained 37% of the total variability of logGDF11 concentrations (p < 0.001), with only logTSH being a significant predictor of logGDF11. After segregating subjects by TSH levels, those within the low TSH group exhibited significantly decreased (p < 0.05) GDF11 concentrations as compared to the normal TSH group or the high TSH group. A significant correlation of GDF11 levels with logCRP (r = 0.19, p = 0.025) was found. GDF11 levels were not related to the presence of hypertension or cardiopathy. In conclusion, our results show that circulating concentrations of GDF11 are closely associated with TSH concentrations and reduced in subjects with low TSH levels. However, GDF11 is not related to the regulation of energy expenditure. Our data also suggest that GDF11 may be involved in the regulation of inflammation, without relation to cardiac function. Further research is needed to elucidate the role of GDF11 in metabolism and its potential involvement in thyroid pathophysiology.
Autores: Ezquerro, S.; Mocha, F.; Frühbeck, Gema; et al.
ISSN 0021-972X  Vol. 104  Nº 1  2019  págs. 21 - 37
CONTEXT: Human obesity is associated with increased circulating TNF-¿, a proinflammatory cytokine that induces hepatocyte cell death. OBJECTIVE: The potential beneficial effects of acylated and desacyl ghrelin in the progression of nonalcoholic fatty liver disease (NAFLD) to nonalcoholic steatohepatitis in obesity via the inhibition of TNF-¿-induced hepatocyte apoptosis, autophagic cell death, and pyroptosis were investigated. DESIGN, SETTINGS, AND PARTICIPANTS: Plasma ghrelin isoforms and TNF-¿ were measured in 158 participants, and hepatocyte cell death was evaluated in liver biopsies from 76 patients with morbid obesity undergoing bariatric surgery with available liver echography and pathology analysis. The effect of acylated and desacyl ghrelin on basal and TNF-¿-induced cell death was determined in vitro in human HepG2 hepatocytes. RESULTS: Circulating TNF-¿ and the acylated/desacyl ghrelin ratio were increased, whereas desacyl ghrelin levels were decreased in patients with obesity and NAFLD. Six months after bariatric surgery, decreased acylated/desacyl ghrelin levels, and improved hepatic function were found. Patients with obesity and type 2 diabetes showed increased hepatic ghrelin O-acyltransferase transcripts as well as an increased hepatic apoptosis, pyroptosis, and compromised autophagy. In HepG2 hepatocytes, acylated and desacyl ghrelin treatment reduced TNF-¿-induced apoptosis, evidenced by lower caspase-8 and caspase-3 cleavage, as well as TUNEL-positive cells and pyroptosis, revealed by decreased caspase-1 activation and lower high-mobility group box 1 expression. Moreover, acylated ghrelin suppressed TNF-¿-activated hepatocyte autophagy, as evidenced by a decreased LC3B-II/I ratio and increased p62 accumulation via AMPK/mTOR. CONCLUSIONS: Ghrelin constitutes a protective factor against hepatocyte cell death. The increased acylated/desacyl ghrelin ratio in patients with obesity and NAFLD might constitute a compensatory mechanism to overcome TNF-¿-induced hepatocyte apoptosis, autophagy, and pyroptosis.
Autores: Ezquerro, S. ; Mocha, F.; Frühbeck, Gema; et al.
ISSN 0014-2972  Vol. 49  Nº Supl. 1  2019  págs. 79 - 80
Autores: Conchillo, María de los Ángeles; et al.
ISSN 0954-691X  Vol. 28  Nº 2  2016  págs. 139 - 145
Objective Hypermetabolism in cirrhosis is associated with a high risk of complications and mortality. However, studies about underlying mechanisms are usually focussed on isolated potential determinants and specific etiologies, with contradictory results. We aimed at investigating differences in nutrition, metabolic hormones, and hepatic function between hypermetabolic and nonhypermetabolic men with cirrhosis of the liver. Patients and methods We prospectively enrolled 48 male cirrhotic inpatients. We evaluated their resting energy expenditure (REE) and substrate utilization by indirect calorimetry, body composition by dual-energy X-ray absorptiometry, liver function, and levels of major hormones involved in energy metabolism by serum sample tests. Patients with ascites, specific metabolic disturbances, and hepatocellular carcinoma were excluded. Results REE and REE adjusted per fat-free mass (FFM) were significantly increased in cirrhotic patients. Overall, 58.3% of cirrhotic patients were classified as hypermetabolic. Groups did not differ significantly in age, etiology of cirrhosis, liver function, presence of ascites, use of diuretics, â-blockers, or presence of transjugular intrahepatic portosystemic shunts. Hypermetabolic cirrhotic patients had lower weight, BMI (P< 0.05), nonprotein respiratory quotient (P< 0.01), leptin (P<0.05), and leptin adjusted per fat mass (FM) (P<0.05), but higher FFM% (P< 0.05) and insulin resistance [homeostatic model assessment-insulin resistance (HOMA-IR)] (P<0.05). Only HOMA-IR, leptin/FM, and FFM% were independently related to the presence of hypermetabolism. Conclusion Hypermetabolic cirrhotic men are characterized by lower weight, higher FFM%, insulin resistance, and lower leptin/FM when compared with nonhypermetabolic men. HOMA-IR, FFM%, and leptin/FM were independently associated with hypermetabolism, and may serve as easily detectable markers of this condition in daily clinical practice.
Autores: Mugueta, Carmen;
ISSN 1577-3558  Vol. 14   Nº 1  2013  págs. 129 - 145
Autores: Solas, Maite; Aisa, Bárbara; Tordera, R.M.; et al.
ISSN 0006-3002  Vol. 1832  Nº 12  2013  págs. 2332 - 2339
It is becoming evident that chronic exposure to stress not only might result in insulin resistance or cognitive deficits, but may also be considered a risk factor for pathologies such as depression or Alzheimer's disease (AD). There is great interest in determining the molecular mechanisms underlying interactions between stress, aging, memory and Alzheimer's disease (AD). We have used the chronic mild stress (CMS) model to study the effects of chronic stress on the aging process and the development of central insulin resistance and AD pathology. CMS aged mice showed cognitive impairments in the novel object recognition test. In addition, CMS aged mice displayed both peripheral insulin resistance, as shown by HOMA index, and decreased hippocampal levels of pIRS and downstream intracellular signaling (pAKT, pGSK and pERK1/2). Interestingly, there was a significant increase in both C99:C83 ratio and BACE1 levels in the hippocampus of CMS aged mice. Increased expression of the AD marker pTau was also found in stressed aged mice. Increased expression of the stress-activated protein kinase JNK was found in CMS aged mice, accompanied by significant decreases in glucocorticoid receptor (GR) expression and increases in mineralocorticoid receptor (MR) expression. It is suggested that the interaction of stress with aging should be considered when studying determinants of the onset and progression of AD.
Autores: Rodríguez, Amaia; Gómez-Ambrosi, J; Catalán, V; et al.
Revista: Diabetologia
ISSN 0012-186X  Vol. 55  Nº 11  2012  págs. 3038 - 3050
Autores: Varo, N; Mugueta, Carmen; et al.
Revista: Nutricion Hospitalaria
ISSN 0212-1611  Vol. 26  Nº 1  2011  págs. 144 - 151
Autores: Gil, Francisco Javier; Aisa, Bárbara; et al.
ISSN 1387-2877  Vol. 22  Nº 3  2010  págs. 829 - 838
The present work investigated the involvement of cortisol and its receptors, glucocorticoid receptor (GR) and mineralocorticoid receptor (MR), in Alzheimer's disease (AD). Cortisol was measured in cerebrospinal fluid (CSF) samples from controls, mild cognitive impairment (MCI), progressive MCI evolving to AD, and AD. CSF cortisol levels do not seem to have a prognostic value, as increases in cortisol levels were found only in AD patients. GR expression was decreased while MR expression was increased in the frontal cortex of AD. When considering degeneration (ratio to synaptophysin and the post-synaptic marker PSD95), GR expression was similar between controls and AD, suggesting that GR loss was due to synaptic degeneration in AD. Increases in cortisol levels and MR expression were associated to an apolipoprotein E4 genotype. Cognitive status was negatively associated to CSF cortisol. In apolipoprotein E4 carriers, MR but not GR expression, negatively correlated to Mini-Mental Status Examination score and positively correlated to frontal cortex amyloid-ß levels. It is concluded that there is a dysregulation of the hypothalamus-pituitary-adrenal axis in AD that seems to be consequence rather than cause of AD.
Autores: Gil, Francisco Javier; Solas, Maite; et al.
Revista: Journal of Alzheimer s Disease
ISSN 1387-2877  Vol. 22  Nº 2  2010  págs. 405 - 413
Previous studies have failed to reach consensus on insulin levels in cerebrospinal fluid of Alzheimer's disease (AD) patients and on its relation to pathological features. We performed a new analysis in patients at different stages of AD, and investigated the relationship of insulin levels with biochemical disease markers and with cognitive score. We included 99 patients from our Memory Clinic (Karolinska University Hospital, Sweden), including: 27 patients with mild AD, 13 that progressed from mild cognitive impairment (MCI) to AD in two years time, 26 with MCI stable after two years, and 33 with subjective cognitive impairment. Insulin was significantly decreased in the cerebrospinal fluid of both women and men with mild AD. Insulin deficits were seen in women belonging to both MCI groups, suggesting that this occurs earlier than in men. Insulin was positively associated with amyloid-ß 1-42 (Aß1-42) levels and cognitive score. Furthermore, total-tau/(Aß1-42*insulin) ratio showed strikingly better sensitivity and specificity than the total-tau/Aß1-42 ratio for early AD diagnosis in women.
Autores: Solas, Maite; Aisa, Bárbara; Mugueta, Carmen; et al.
ISSN 0893-133X  Vol. 35  Nº 8  2010  págs. 1664 - 1673
There is much interest in understanding the mechanisms responsible for interactions among stress, aging, memory and Alzheimer's disease. Glucocorticoid secretion associated with early life stress may contribute to the variability of the aging process and to the development of neuro- and psychopathologies. Maternal separation (MS), a model of early life stress in which rats experience 3 h of daily separation from the dam during the first 3 weeks of life, was used to study the interactions between stress and aging. Young (3 months) MS rats showed an altered hypothalamic-pituitary-adrenal (HPA) axis reactivity, depressive-like behavior in the Porsolt swimming test and cognitive impairments in the Morris water maze and new object recognition test that persisted in aged (18 months) rats. Levels of insulin receptor, phosphorylated insulin receptor and markers of downstream signaling pathways (pAkt, pGSK3 beta, pTau, and pERK1 levels) were significantly decreased in aged rats. There was a significant decrease in pERK2 and in the plasticity marker ARC in MS aged rats compared with single MS or aged rats. It is interesting to note that there was a significant increase in the C99 : C83 ratio, A beta levels, and BACE1 levels the hippocampus of MS aged rats, suggesting that in aged rats subjected to early life stress, there was an increase in the amyloidogenic processing of amyloid precursor protein (APP). These results are integrated in a tentative mechanism through which aging interplay with stress to influence cognition as the basis of Alzheimer disease (AD). The present results may provide the proof-of-concept for the use of glucocorticoid-/insulin-related drugs in the treatment of AD.
Autores: Salgado, Josefa; González, Álvaro; Alegre, Estíbaliz; et al.
Libro:  Principios de bioquímica clínica y patología molecular
2014  págs. 341-346
Complejo de glucoproteínas asociadas con la distrofina, distrofias musculares de Duchenne y Becker, técnicas bioquímicas diagnósticas de las distrofias musculares de Duchenne y Becker, otras distrofias.
Autores: González, Álvaro; Alegre, Estíbaliz; Monreal, José Ignacio; et al.
Libro:  Principios de bioquímica clínica y patología molecular
2014  págs. 347-353
Cadena respiratoria mitocondrial y fosforilación oxidativa, ADN mitocondrial, origen de las proteínas mitocondriales, alteraciones del ADN mitocondrial y envejecimiento, enfermedades mitocondriales o citopatías mitocondriales, estudio bioquímico general de las citopatías mitocondriales.
Autores: Salgado, Josefa; González, Álvaro; Alegre, Estíbaliz; et al.
Libro:  Principios de bioquímica clínica y patología molecular
2014  págs. 275 - 285
Desarrollo tumoral, marcadores tumorales, determinación de los marcadores tumorales, principales marcadores tumorales séricos, aplicación de los marcadores tumorales farmacogenómica y farmacogenética.
Autores: Mugueta, Carmen; Varo, N;
Libro:  Fundamentos de Nutrición y Dietética. Bases metodológicas y aplicaciones
2011  págs. 251 - 255
Autores: Varo, N; Mugueta, Carmen;
Libro:  Fundamentos de Nutrición y Dietética. Bases metodológicas y aplicaciones
2011  págs. 263 - 267




1. Premio para la comunicación ¿Estudio de los niveles de serotonina durante el trasplante hepático¿ en el XV Congreso Nacional de la Sociedad Española de Bioquímica Clínica y Patología Molecular, celebrado en Madrid del 31 de Octubre al 2 de Noviembre de 1996. 2. Premio para la comunicación ¿Record of preanalytical errors in the laboratory information system¿ en el XXII National Congress of the Spanish Society of Clinical Biochemistry and Molecular Pathology, celebrado en Barcelona del 1 al 5 de Junio de 2003. Primer firmante. 3. Premio para la comunicación "Niveles de insulina en el líquido cefalorraquídeo de pacientes con enfermedad de Alzheimer" en el III Congreso Nacional del Laboratorio Clínico. Valencia, 14-16 octubre de 2009. Primer firmante. 4. Primer premio SEEDO 2013 de Investigación básica en Obesidad. A. Rodríguez, J. Gómez-Ambrosi, V. Catalán, F. Rotellar, V. Valentí, C. Silva, C. Mugueta, M. R. Pulido, R. Vázquez, J. Salvador, M. M. Malagón, I. Colina, G. Frühbeck. The ghrelin O-acyltransferase¿ghrelin system reduces TNF-¿-induced apoptosis and autophagy in human visceral adipocytes. Diabetologia 2012 Nov;55(11):3038-50. doi: 10.1007/s00125-012-2671-5. Epub 2012 Aug 7.