Torre, R. (Rafael) de la
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- Reduced Plasma Orexin-A Concentrations are Associated with Cognitive Deficits in Anorexia Nerviosa(Springer Science and Business Media LLC, 2019) Sánchez-Díaz, I. (Isabel); Fernandez-Garcia, J.C. (José C.); Casanueva, F.F. (Felipe F.); Garrido-Sánchez, L. (Lourdes); Tinahones, F.J. (Francisco J.); Torre, R. (Rafael) de la; Vintró-Alcaraz, C. (Cristina); Frühbeck, G. (Gema); Steward, T. (Trevor); Menchon, J.M. (José M.); Crujeiras, A.B. (Ana B.); Granero, R. (Roser); Baños, R. (Rosa); Agüera, Z. (Zaida); Jimenez-Murcia, S. (Susana); Rodriguez, A. (Amaia); Riesco, N. (Nadine); Botella, C. (Cristina); Ortega, F.J. (Francisco J.); Fernandez-Aranda, F. (Fernando); Sauchelli, S. (Sarah); Mestre-Bach, G. (Gemma); Fernandez-Real, J.M. (José Manuel)Orexins/hypocretins are neuropeptides implicated in numerous processes, including food intake and cognition. The role of these peptides in the psychopathology of anorexia nervosa (AN) remains poorly understood. The aim of the current study was to evaluate the associations between plasma orexin-A (OXA) concentrations and neuropsychological functioning in adult women with AN, and a matched control group. Fasting plasma OXA concentrations were taken in 51 females with AN and in 51 matched healthy controls. Set-shifting was assessed using the Wisconsin Card Sorting Test (WCST), whereas decision making was measured using the Iowa Gambling Task (IGT). The AN group exhibited lower plasma OXA levels than the HC group. Lower mean scores were obtained on the IGT in AN patients. WCST perseverative errors were significantly higher in the AN group compared to HC. In both the AN and HC group, OXA levels were negatively correlated with WCST non-perseverative errors. Reduced plasma OXA concentrations were found to be associated with set-shifting impairments in AN. Taking into consideration the function of orexins in promoting arousal and cognitive flexibility, future studies should explore whether orexin partly underpins the cognitive impairments found in AN.
- Association of irisin with fat mass, resting energy expenditure, and daily activity in conditions of extreme body mass index(Hindawi Publishing Corporation, 2014) Fernandez-Garcia, J.C. (José C.); Fagundo, A.B. (Ana B.); Casanueva, F.F. (Felipe F.); Amil, M. (María); Tinahones, F.J. (Francisco J.); Torre, R. (Rafael) de la; Pardo, M. (M.); Frühbeck, G. (Gema); Estivill, X. (Xavier); Crujeiras, A.B. (Ana B.); Rodriguez, R. (Roser); Baños, R. (Rosa); Agüera, Z. (Zaida); Jimenez-Murcia, S. (Susana); Gomez-Ambrosi, J. (Javier); Botella, C. (Cristina); Fernandez-Aranda, F. (Fernando); Fernandez-Real, J.M. (José Manuel)FNDC5/irisin has been recently postulated as beneficial in the treatment of obesity and diabetes because it is induced in muscle by exercise, increasing energy expenditure. However, recent reports have shown that WAT also secretes irisin and that circulating irisin is elevated in obese subjects. The aim of this study was to evaluate irisin levels in conditions of extreme BMI and its correlation with basal metabolism and daily activity. The study involved 145 female patients, including 96 with extreme BMIs (30 anorexic (AN) and 66 obese (OB)) and 49 healthy normal weight (NW). The plasma irisin levels were significantly elevated in the OB patients compared with the AN and NW patients. Irisin also correlated positively with body weight, BMI, and fat mass. The OB patients exhibited the highest REE and higher daily physical activity compared with the AN patients but lower activity compared with the NW patients. The irisin levels were inversely correlated with daily physical activity and directly correlated with REE. Fat mass contributed to most of the variability of the irisin plasma levels independently of the other studied parameters. Conclusion. Irisin levels are influenced by energy expenditure independently of daily physical activity but fat mass is the main contributing factor.
- Moderate-vigorous physical activity across body mass index in females: moderating effect of endocannabinoids and temperament(Public Library of Science, 2014) Fernandez-Garcia, J.C. (José C.); Fagundo, A.B. (Ana B.); Casanueva, F.F. (Felipe F.); Tinahones, F.J. (Francisco J.); Arcelus, J. (Jon); Torre, R. (Rafael) de la; Frühbeck, G. (Gema); Granero, R. (Roser); Rodriguez, R. (Roser); Gonzalez, M.L. (Marcela L.); Pastor, A. (Antoni); Baños, R. (Rosa); Agüera, Z. (Zaida); Jimenez-Murcia, S. (Susana); Gomez-Ambrosi, J. (Javier); Botella, C. (Cristina); Miro, J. (Jordi); Fernandez-Aranda, F. (Fernando); Sauchelli, S. (Sarah); Fernandez-Real, J.M. (José Manuel)BACKGROUND: Endocannabinoids and temperament traits have been linked to both physical activity and body mass index (BMI) however no study has explored how these factors interact in females. The aims of this cross-sectional study were to 1) examine differences among distinct BMI groups on daytime physical activity and time spent in moderate-vigorous physical activity (MVPA), temperament traits and plasma endocannabinoid concentrations; and 2) explore the association and interaction between MVPA, temperament, endocannabinoids and BMI. METHODS: Physical activity was measured with the wrist-worn accelerometer Actiwatch AW7, in a sample of 189 female participants (43 morbid obese, 30 obese, and 116 healthy-weight controls). The Temperament and Character Inventory-Revised questionnaire was used to assess personality traits. BMI was calculated by bioelectrical impedance analysis via the TANITA digital scale. Blood analyses were conducted to measure levels of endocannabinoids and endocannabinoid-related compounds. Path-analysis was performed to examine the association between predictive variables and MVPA. RESULTS: Obese groups showed lower MVPA and dysfunctional temperament traits compared to healthy-weight controls. Plasma concentrations of 2-arachidonoylglyceryl (2-AG) were greater in obese groups. Path-analysis identified a direct effect between greater MVPA and low BMI (b = -0.13, p = .039) and high MVPA levels were associated with elevated anandamide (AEA) levels (b = 0.16, p = .049) and N-oleylethanolamide (OEA) levels (b = 0.22, p = .004), as well as high Novelty seeking (b = 0.18, p<.001) and low Harm avoidance (b = -0.16, p<.001). CONCLUSIONS: Obese individuals showed a distinct temperament profile and circulating endocannabinoids compared to controls. Temperament and endocannabinoids may act as moderators of the low MVPA in obesity.
- Physical fitness and physical activity association with cognitive function and quality of life: baseline cross-sectional analysis of the PREDIMED-Plus trial(Springer Nature, 2020) Buil-Cosiales, P. (Pilar); Colmenarejo, G. (Gonzalo); Martinez, J.A. (José Alfredo); Martinez-Gonzalez, M.A. (Miguel Ángel); Micó-Pérez, R.M. (Rafael Manuel); Galilea-Zabalza, I. (Iñigo); Garcia-Rios, A. (Antonio); Daimiel, L. (Lidia); Tinahones, F.J. (Francisco J.); Vioque, J. (Jesús); Torre, R. (Rafael) de la; Zulet, M.A. (María Ángeles); Tur, J.A. (Josep A.); Romaguera, D. (Dora); Lapetra, J. (José); Paz-Graniel, I. (Indira); Schröder, H. (Helmut); López-Miranda, J. (José); Galdon, A. (Alba); Galmes-Panades, A.M. (Aina M.); Matia, P. (Pilar); Ros, E. (Emilio); Ordovas, J.M. (Jose Manuel); Micó, V. (Victor); Alonso-Gomez, A. (Ángel); Wärnberg, J. (Julia); Estruch, R. (Ramón); Vazquez-Ruiz, Z. (Zenaida); Diaz-Lopez, A. (Andres); Gaforio, J.J. (José Juan); Serra-Majem, L. (Luis); Corella, D. (Dolores); Vidal, J. (Josep); Pinto, X. (Xavier); Salas-Salvado, J. (Jordi); Cano-Ibañez, N. (Naomi); Sorli, J.V. (Jose V.); Cuenca-Royo, A. (Aida); Gisbert-Sellés, C. (Cristina)Physical activity (PA) has been hypothesized to be effective to maintaining cognitive function and delay cognitive decline in the elderly, but physical fitness (PF) could be a better predictor of cognitive function. We aimed to study the association between PA and PF with cognitive function and quality of life using cross-sectional data from 6874 participants of the PREDIMED-Plus trial (64.9 ± 4.9 years, 48.5% female). PF and PA were measured with a Chair Stand Test, the REGICOR and Rapid Assessment Physical Activity questionnaires. Cognitive function was measured with Mini-mental State Examination, Control Oral Word Association Test, Trail Making Test and Digit Span tests; whereas health-related quality of life was assessed with the SF36-HRQL test. Cognitive and quality of life scores were compared among PF quartiles and PA levels (low, moderate and high) with ANCOVA and with Chair Stand repetitions and energy expenditure from total PA with multivariable linear regression adjusted for confounding factors. PF associated with higher scores in phonemic and semantic verbal fluency tests and with lower TMT A time. However, PA was not associated with the neurocognitive parameters evaluated. Both PF and PA levels were strongly associated with a better quality of life. We concluded that PF, but not PA, is associated with a better cognitive function. This trial was retrospectively registered at the International Standard Randomized Controlled Trial (ISRCTN89898870, https://www.isrctn.com/ISRCTN89898870?q=ISRCTN89898870&filters=&sort=&offset=1&totalResults=1&page=1&pageSize=10&searchType=basic-search) on 07/24/2014.
- Smelling the dark proteome: Functional characterization of PITH domain-containing protein 1 (C1orf128) in olfactory metabolism(ACS Publications, 2020) Elortza, F. (Felix); Perez-Mediavilla, L.A. (Luis Alberto); Azkargorta, M. (Mikel); Torre, R. (Rafael) de la; Ferrer, I. (Isidro); Fernandez-Irigoyen, J. (Joaquín); Ohigashi, I. (Izumi); Iloro, I. (Ibon); Kondo, H. (Hiroyuki); Lachén-Montes, M. (Mercedes); Mendizuri, N. (Naroa); Santamaria, E. (Enrique); Ausin, K. (Karina); Robledo-Ramón, P. (Patricia)The Human Proteome Project (HPP) consortium aims to functionally characterize the dark proteome. On the basis of the relevance of olfaction in early neurodegeneration, we have analyzed the dark proteome using data mining in public resources and omics data sets derived from the human olfactory system. Multiple dark proteins localize at synaptic terminals and may be involved in amyloidopathies such as Alzheimer’s disease (AD). We have characterized the dark PITH domain-containing protein 1 (PITHD1) in olfactory metabolism using bioinformatics, proteomics, in vitro and in vivo studies, and neuropathology. PITHD1–/– mice exhibit olfactory bulb (OB) proteome changes related to synaptic transmission, cognition, and memory. OB PITHD1 expression increases with age in wild-type (WT) mice and decreases in Tg2576 AD mice at late stages. The analysis across 6 neurological disorders reveals that olfactory tract (OT) PITHD1 is specifically upregulated in human AD. Stimulation of olfactory neuroepithelial (ON) cells with PITHD1 alters the ON phosphoproteome, modifies the proliferation rate, and induces a pro-inflammatory phenotype. This workflow applied by the Spanish C-HPP and Human Brain Proteome Project (HBPP) teams across the ON-OB-OT axis can be adapted as a guidance to decipher functional features of dark proteins. Data are available via ProteomeXchange with identifiers PXD018784 and PXD021634.
- Modulation of the endocannabinoids N-arachidonoylethanolamine (AEA) and 2-arachidonoylglycerol (2-AG) on executive functions in humans(Public Library of Science, 2013-06-19) Fernandez-Garcia, J.C. (José C.); Fagundo, A.B. (Ana B.); Casanueva, F.F. (Felipe F.); Tinahones, F.J. (Francisco J.); Torre, R. (Rafael) de la; Moragrega, I. (Inés); Tarrega, S. (Salomé); Pino-Gutierrez, A. (Amparo) del; Frühbeck, G. (Gema); Menchon, J.M. (José M.); Granero, R. (Roser); Rodriguez, R. (Roser); Pastor, A. (Antoni); Baños, R. (Rosa); Agüera, Z. (Zaida); Jimenez-Murcia, S. (Susana); Gomez-Ambrosi, J. (Javier); Botella, C. (Cristina); Fernandez-Aranda, F. (Fernando); Fernandez-Real, J.M. (José Manuel)Animal studies point to an implication of the endocannabinoid system on executive functions. In humans, several studies have suggested an association between acute or chronic use of exogenous cannabinoids (Δ9-tetrahydrocannabinol) and executive impairments. However, to date, no published reports establish the relationship between endocannabinoids, as biomarkers of the cannabinoid neurotransmission system, and executive functioning in humans. The aim of the present study was to explore the association between circulating levels of plasma endocannabinoids N-arachidonoylethanolamine (AEA) and 2-Arachidonoylglycerol (2-AG) and executive functions (decision making, response inhibition and cognitive flexibility) in healthy subjects. One hundred and fifty seven subjects were included and assessed with the Wisconsin Card Sorting Test; Stroop Color and Word Test; and Iowa Gambling Task. All participants were female, aged between 18 and 60 years and spoke Spanish as their first language. Results showed a negative correlation between 2-AG and cognitive flexibility performance (r = -.37; p<.05). A positive correlation was found between AEA concentrations and both cognitive flexibility (r = .59; p<.05) and decision making performance (r = .23; P<.05). There was no significant correlation between either 2-AG (r = -.17) or AEA (r = -.08) concentrations and inhibition response. These results show, in humans, a relevant modulation of the endocannabinoid system on prefrontal-dependent cognitive functioning. The present study might have significant implications for the underlying executive alterations described in some psychiatric disorders currently associated with endocannabinoids deregulation (namely drug abuse/dependence, depression, obesity and eating disorders). Understanding the neurobiology of their dysexecutive profile might certainly contribute to the development of new treatments and pharmacological approaches.