Browsing by MeSH term "Oleic Acids"
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Publication Beneficial effects of dietary supplementation with olive oil, oleic acid, or hydroxytyrosol in metabolic syndrome: Systematic review and meta-analysis(Elsevier, 2021-08-20) Pastor, Rosario; Bouzas, Cristina; Tur, Josep ABackground and aims: Olive oil and components might have a beneficial effect on Metabolic Syndrome (MetS). The aim of this review and meta-analysis was to assess whether those effects are related to hydroxytyrosol or oleic acid contents, or the combination of them as olive oil, and how powerful is this effect. Methods: A systematic literature search was performed in MEDLINE via Pubmed, Web of Science (WOS) core collection, and Virtual Health Library (VHL) via LILACS and IBECS (Spain). MeSH terms used were obesity, body weight, body mass index, adipose tissue, lipid metabolism, LDL, HDL, VLDL, insulin resistance, glucose, insulin, hypertension, arterial pressure, olive oil, oleic acid, and other (non-MeSH) terms: total antioxidant capacity, total antioxidant status, hydroxytyrosol (PROSPERO ID: CRD42021247614). Results of the included studies were meta-analyzed with the RevMan 5.3 program, assuming a random effects model. Results: 76 research articles (67 different trials) were identified. Hydroxytyrosol had no effect on MetS [combined standardized mean differences (SMD) = 0.01 (CI 95%: [-0.23, 0.25], I-2 = 83%; p = 0.920)]. Oleic acid had no significant beneficial effect on MetS [SMD = 0.03 (CI 95%: [-0.01, 0.07], I-2 = 0%); p = 0.150], but it improved lipid profile [SMD = 0.06 (CI 95%: [-0.00, 0.12], I-2 = 0%); p = 0. 050]. Olive oil had no effect on MetS [SMD =-0.01 (CI 95%: [-0.05, 0.03]), I-2 = 55%; p = 0.550)]. The supplementation with hydroxytyrosol, oleic acid or olive oil showed a beneficial effect on antioxidant capacity related to components of MetS [SMD = 0.31 (CI 95%: [-0.34, 0.95], I-2 = 81%)]; p = 0.35). Conclusion: Most research articles compared olive oil and oleic acid with other strategies specially designed for MetS management. Our findings suggest that olive oil or oleic acid consumption are as good as the other strategies to manage MetS.Publication Biophysical and biological impact on the structure and IgE-binding of the interaction of the olive pollen allergen Ole e 7 with lipids.(Elsevier, 2020) Oeo-Santos, Carmen; López-Rodríguez, Juan Carlos; García-Mouton, Cristina; San Segundo-Acosta, Pablo; Jurado, Aurora; García-Álvarez, Begoña; Pérez-Gil, Jesús; Villalba, Mayte; Barderas Manchado, Rodrigo; Cruz, Antonio; Moreno-Aguilar, Carmen; Ministerio de Economía y Competitividad (España); Ministerio de Ciencia, Innovación y Universidades (España); Comunidad de Madrid (España); Instituto de Salud Carlos III; Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF); Regional Government of Andalusia (España); Fundación AlergosurOle e 7 allergen from Olea europaea pollen possesses a major clinical relevance because it produces severe symptoms, such as anaphylaxis, in allergic patients exposed to high olive pollen counts. Ole e 7 is a non-specific lipid transfer protein (nsLTP) characterized by the presence of a tunnel-like hydrophobic cavity, which may be suitable for hosting and, thus, transporting lipids -as it has been described for other nsLTPs-. The identification of the primary amino acid sequence of Ole e 7, and its production as a recombinant allergen, allowed characterizing its lipid-binding properties and its effect at air-liquid interfaces. Fluorescence and interferometry experiments were performed using different phospholipid molecular species and free fatty acids to analyse the lipid-binding ability and specificity of the allergen. Molecular modelling of the allergen was used to determine the potential regions involved in lipid interaction. Changes in Ole e 7 structure after lipid interaction were analysed by circular dichroism. Changes in the IgE binding upon ligand interaction were determined by ELISA. Wilhelmy balance measurements and fluorescence surfactant adsorption tests were performed to analyse the surface activity of the allergen. Using these different approaches, we have demonstrated the ability of Ole e 7 to interact and bind to a wide range of lipids, especially negatively charged phospholipids and oleic acid. We have also identified the protein structural regions and the residues potentially involved in that interaction, suggesting how lipid-protein interactions could define the behaviour of the allergen once inhaled at the airways.Publication Exposure to a Highly Caloric Palatable Diet During Pregestational and Gestational Periods Affects Hypothalamic and Hippocampal Endocannabinoid Levels at Birth and Induces Adiposity and Anxiety-Like Behaviors in Male Rat Offspring.(Frontiers Media, 2016-01-06) Ramírez-López, María Teresa; Vázquez, Mariam; Bindila, Laura; Lomazzo, Ermelinda; Hofmann, Clementine; Blanco, Rosario Noemí; Alén, Francisco; Antón, María; Decara, Juan; Ouro, Daniel; Orio, Laura; Suarez, Juan; Lutz, Beat; Rodríguez de Fonseca, Fernando; Gómez de Heras, Raquel; [Ramírez-López,MT; Vázquez,M; Blanco,RN; Alén,F; Antón,M; Ouro,L; Rodríguez de Fonseca,F; Gómez de Heras,R] Departamento de Psicobiología, Facultad de Psicología, Universidad Complutense de Madrid, Madrid, Spain. [Vázquez,M; Degara,J; Suarez,J; Rodríguez de Fonseca,F] Unidad de Gestión Clínica de Salud Mental, Instituto IBIMA, Hospital Regional Universitario de Málaga, Universidad de Málaga, Málaga, Spain. [Bindila,L; Lomazzo,E; Hofmann,C; Lutz,B] Institute of Physiological Chemistry, University Medical Center of the Johannes Gutenberg University of Mainz, Mainz, Germany.Exposure to unbalanced diets during pre-gestational and gestational periods may result in long-term alterations in metabolism and behavior. The contribution of the endocannabinoid system to these long-term adaptive responses is unknown. In the present study, we investigated the impact of female rat exposure to a hypercaloric-hypoproteic palatable diet during pre-gestational, gestational and lactational periods on the development of male offspring. In addition, the hypothalamic and hippocampal endocannabinoid contents at birth and the behavioral performance in adulthood were investigated. Exposure to a palatable diet resulted in low weight offspring who exhibited low hypothalamic contents of arachidonic acid and the two major endocannabinoids (anandamide and 2-arachidonoylglycerol) at birth. Palmitoylethanolamide, but not oleoylethanolamide, also decreased. Additionally, pups from palatable diet-fed dams displayed lower levels of anandamide and palmitoylethanolamide in the hippocampus. The low-weight male offspring, born from palatable diet exposed mothers, gained less weight during lactation and although they recovered weight during the post-weaning period, they developed abdominal adiposity in adulthood. These animals exhibited anxiety-like behavior in the elevated plus-maze and open field test and a low preference for a chocolate diet in a food preference test, indicating that maternal exposure to a hypercaloric diet induces long-term behavioral alterations in male offspring. These results suggest that maternal diet alterations in the function of the endogenous cannabinoid system can mediate the observed phenotype of the offspring, since both hypothalamic and hippocampal endocannabinoids regulate feeding, metabolic adaptions to caloric diets, learning, memory, and emotions.Publication Oleic Acid Protects Against Insulin Resistance by Regulating the Genes Related to the PI3K Signaling Pathway(Multidisciplinary Digital Publishing Institute (MDPI), 2020-08-12) López-Gómez, Carlos; Santiago-Fernández, Concepción; García-Serrano, Sara; García-Escobar, Eva; Gutiérrez-Repiso, Carolina; Rodríguez-Díaz, Cristina; Ho-Plágaro, Ailec; Martín-Reyes, Flores; Garrido-Sánchez, Lourdes; Valdés, Sergio; Rodríguez-Cañete, Alberto; Rodríguez-Pacheco, Francisca; García-Fuentes, Eduardo; [López-Gómez,C; Santiago-Fernández,C; Rodríguez-Díaz,C; Ho-Plágaro,A; Martín-Reyes,F; Rodríguez-Pacheco,F; García-Fuentes,E] Unidad de Gestión Clínica de Aparato Digestivo, Hospital Universitario Virgen de la Victoria/Instituto de Investigación Biomédica de Málaga-IBIMA, Málaga, Spain. [García-Serrano,S; García-Escobar,E; Valdés,S] Unidad de Gestión Clínica de Endocrinología y Nutrición, Hospital Regional Universitario de Málaga/Instituto de Investigación Biomédica de Málaga-IBIMA, Málaga, Spain. [García-Serrano,S; García-Escobar,E; Valdés,S; Rodríguez-Pacheco,F] CIBER de Diabetes y Enfermedades Metabólicas Asociadas-CIBERDEM, Málaga, Spain. [Gutiérrez-Repiso,C; Garrido-Sánchez,L] Unidad de Gestión Clínica de Endocrinología y Nutrición, Hospital Universitario Virgen de la Victoria/Instituto de Investigación Biomédica de Málaga-IBIMA, Málaga, Spain. [Garrido-Sánchez,L] CIBER Fisiopatología de la Obesidad y Nutrición-CIBEROBN, Málaga, Spain. [Rodríguez-Cañete,A] Unidad de Gestión Clínica de Cirugía General, Digestiva y Trasplantes, Hospital Regional Universitario de Málaga, Málaga, Spain.The effects of different types of fatty acids on the gene expression of key players in the IRS1/PI3K signaling pathway have been poorly studied. Material and Methods: We analyzed IRS1, p85α, and p110β mRNA expression and the fatty acid composition of phospholipids in visceral adipose tissue from patients with morbid obesity and from non-obese patients. Moreover, we analyzed the expression of those genes in visceral adipocytes incubated with oleic, linoleic, palmitic and dosahexaenoic acids. Results: We found a reduced IRS1 expression in patients with morbid obesity, independent of insulin resistance, and a reduced p110β expression in those with lower insulin resistance. A positive correlation was found between p85α and stearic acid, and between IRS1 and p110β with palmitic and dosahexaenoic acid. In contrast, a negative correlation was found between p85α and oleic acid, and between IRS1 and p110β with linoleic, arachidonic and adrenic acid. Incubation with palmitic acid decreased IRS1 expression. p85α was down-regulated after incubation with oleic and dosahexaenoic acid and up-regulated with palmitic acid. p110β expression was increased and decreased after incubation with oleic and palmitic acid, respectively. The ratio p85α/p110β was decreased by oleic and dosahexaenoic acid and increased by palmitic acid. Conclusions: Our in vitro results suggest a detrimental role of palmitic acid on the expression of gene related to insulin signaling pathway, with oleic acid being the one with the higher and more beneficial effects. DHA had a slight beneficial effect. Fatty acid-induced regulation of genes related to the IRS1/PI3K pathway may be a novel mechanism by which fatty acids regulate insulin sensitivity in visceral adipocytes.Publication Palmitoleoylethanolamide Is an Efficient Anti-Obesity Endogenous Compound: Comparison with Oleylethanolamide in Diet-Induced Obesity(Multidisciplinary Digital Publishing Institute (MDPI), 2021-07-28) Tovar, Rubén; Gavito, Ana Luisa; Vargas, Antonio; Soverchia, Laura; Hernandez-Folgado, Laura; Jagerovic, Nadine; Baixeras, Elena; Ciccocioppo, Roberto; Rodríguez de Fonseca, Fernando; Decara, Juan; [Tovar,R; Gavito,AL; Vargas,A; Rodríguez de Fonseca,F; Decara,J] Instituto de Investigación Biomédica de Málaga (IBIMA), Hospital Universitario Regional de Málaga, UGC Salud Mental, Avda. Carlos Haya, Pabellón de Gobierno, Málaga, Spain. [Tovar,R] Facultad de Medicina, Universidad de Málaga, Málaga, Spain. [Soverchia,L; Ciccocioppo,R; Decara,J] Pharmacology Unit, School of Pharmacy, University of Camerino, Camerino, Italy. [Hernandez-Folgado,L; Jagerovic,N] Instituto de Química Médica, CSIC, Madrid, Spain. [Baixeras,E] Departamento de Bioquímica y Biología Molecular, Facultad de Medicina, Universidad de Málaga, Málaga, Spain.Obesity is currently a major epidemic in the developed world. However, we lack a wide range of effective pharmacological treatments and therapies against obesity, and those approved are not devoid of adverse effects. Dietary components such as palmitoleic acid have been proposed to improve metabolic disbalance in obesity, although the mechanisms involved are not well understood. Both palmitoleic acid (POA) and oleic acid (OA) can be transformed in N-acylethanolamines (NAEs), mediating the effects of dietary POA and OA. To test this hypothesis, here, we study the effects on food intake and body weight gain of palmitoleylethanolamide (POEA) and the OA-derived NAE analogue, oleoylethanolamide (OEA), in Sprague-Dawley rats with a hypercaloric cafeteria diet (HFD). Plasma biochemical metabolites, inflammatory mediators, and lipogenesis-associated liver protein expression were also measured. The results indicate that POEA is able to improve health status in diet-induced obesity, decreasing weight, liver steatosis, inflammation, and dyslipemia. The action of POEA was found to be almost identical to that of OEA, which is an activator of the nuclear peroxisome proliferator receptor alpha (PPARα), and it is structurally related to POEA. These results suggest that the dietary administration of either POA or POEA might be considered as nutritional intervention as complementary treatment for complicated obesity in humans.Publication Perinatal asphyxia results in altered expression of the hippocampal acylethanolamide/endocannabinoid signaling system associated to memory impairments in postweaned rats.(Frontiers Media, 2015-11-03) Blanco, Eduardo; Galeano, Pablo; Holubiec, Mariana I; Romero, Juan I; Logica, Tamara; Rivera, Patricia; Pavón, Francisco-Javier; Suarez, Juan; Capani, Francisco; Rodríguez de Fonseca, Fernando; [Blanco,E,; Rivera,P; Pavón,FJ; Suarez.K: Rodríguez de Fonseca,F] Unidad de Gestión Clínica de Salud Mental, Laboratorio de Medicina Regenerativa, Instituto de Investigación Biomédica de Málaga (IBIMA). Hospital Universitario Regional de Málaga. Universidad de Málaga, Málaga, Spain. [Blanco,E] Departament de Pedagogia i Psicologia, Facultat d’Educació, Psicologia i Treball Social, Universitat de Lleida, Lleida, Spain. [Galeano,P] Instituto de Investigaciones Bioquímicas de Buenos Aires – Consejo Nacional de Investigaciones Científicas y Técnicas. Fundación Instituto Leloir, Buenos Aires, Argentina. [Galeano,P; Holubiec,MI; Romero,JI; Logica,T; Campani,] Facultad de Medicina, Instituto de Investigaciones Cardiológicas “Prof. Dr. Alberto C. Taquini”, Consejo Nacional de Investigaciones Científicas y Técnicas, Universidad de Buenos Aires, Buenos Aires, Argentina.Perinatal asphyxia (PA) is an obstetric complication that strongly affects the CNS. The endocannabinoid system (ECS) is a lipid transmitter system involved in several physiological processes including synaptic plasticity, neurogenesis, memory, and mood. Endocannabinoids, and other acylethanolamides (AEs) without endocannabinoid activity, have recently received growing attention due to their potential neuroprotective functions in neurological disorders, including cerebral ischemia. In the present study, we aimed to analyze the changes produced by PA in the major metabolic enzymes and receptors of the ECS/AEs in the hippocampus using a rodent model of PA. To induce PA, we removed uterine horns from ready-to-deliver rats and immersed them into a water bath during 19 min. Animals delivered spontaneously or by cesarean section were employed as controls. At 1 month of age, cognitive functions were assessed and immunohistochemical procedures were carried out to determine the expression of NeuN and glial fibrillary acidic protein, enzymes responsible for synthesis (DAGLα and NAPE-PLD) and degradation (FAAH) of ECS/AEs and their receptors (CB1 and PPARα) in the hippocampus. Postweaned asphyctic rats showed impaired recognition and spatial reference memory that were accompanied by hippocampal astrogliosis and changes in the expression of enzymes and receptors. The most remarkable findings in asphyctic rats were a decrease in the expression of NAPE-PLD and PPARα in both hippocampal areas CA1 and CA3. In addition, postweaned cesarean delivery rats showed an increase in the immunolabeling for FAAH in the hippocampal CA3 area. Since, NAPE-PLD and PPARα are proteins that participate in the biochemical process of AEs, specially the neuroprotective oleoylethanolamide, these results suggest that PA dysregulates this system. These data encourage conducting future studies using AEs as potential neuroprotective compounds in animal models of PA.Publication Pharmacological blockade of the fatty acid amide hydrolase (FAAH) alters neural proliferation, apoptosis and gliosis in the rat hippocampus, hypothalamus and striatum in a negative energy context.(Frontiers Media, 2015-03-27) Rivera, Patricia; Bindila, Laura; Pastor, Antoni; Pérez-Martín, Margarita; Pavón, Francisco-Javier; Serrano, Antonia; de la Torre, Rafael; Lutz, Beat; Rodríguez de Fonseca, Fernando; Suárez, Juan; [Rivera,P; Pavón,FJ; Serrano,A; Rodríguez de Fonseca,F; Suárez,J] UGC Salud Mental, Instituto de Investigación Biomédica (IBIMA), Universidad de Málaga-Hospital Universitario Regional de Málaga, Málaga, Spain. [Rivera,P; Pavón,FJ; Serrano,A; de la Torre,R; Rodríguez de Fonseca,F; Suárez,J] CIBER OBN, Instituto de Salud Carlos III, Madrid, Spain. [Bindila,L, Lutz,B] Institute of Physiological Chemistry, University Medical Center of the Johannes Gutenberg-University of Mainz, Mainz, Germany. [Pastor,A; de la Torre,R] Institut Hospital del Mar d'Investigacions Mediques, Barcelona, Spain. [Pastor,A] Facultat de Medicina, Universitat Autonoma de Barcelona, Barcelona, Spain. [Pérez-Martín,M] Departamento de Biología Celular, Genética y Fisiología, Instituto de Investigación Biomédica (IBIMA), Universidad de Málaga, Málaga, Spain. [de la Torre, R] Facultat de Ciencies de la Salut i de la Vida, Universitat Pompeu Fabra (CEXS-UPF), Barcelona, Spain.Endocannabinoids participate in the control of neurogenesis, neural cell death and gliosis. The pharmacological effect of the fatty acid amide hydrolase (FAAH) inhibitor URB597, which limits the endocannabinoid degradation, was investigated in the present study. Cell proliferation (phospho-H3(+) or BrdU(+) cells) of the main adult neurogenic zones as well as apoptosis (cleaved caspase-3(+)), astroglia (GFAP(+)), and microglia (Iba1(+) cells) were analyzed in the hippocampus, hypothalamus and striatum of rats intraperitoneally treated with URB597 (0.3 mg/kg/day) at one dose/4-days resting or 5 doses (1 dose/day). Repeated URB597 treatment increased the plasma levels of the N-acylethanolamines oleoylethanolamide, palmitoylethanolamide and arachidonoylethanolamine, reduced the plasma levels of glucose, triglycerides and cholesterol, and induced a transitory body weight decrease. The hippocampi of repeated URB597-treated rats showed a reduced number of phospho-H3(+) and BrdU(+) subgranular cells as well as GFAP(+), Iba1(+) and cleaved caspase-3(+) cells, which was accompanied with decreased hippocampal expression of the cannabinoid CB1 receptor gene Cnr1 and Faah. In the hypothalami of these rats, the number of phospho-H3(+), GFAP(+) and 3-weeks-old BrdU(+) cells was specifically decreased. The reduced striatal expression of CB1 receptor in repeated URB597-treated rats was only associated with a reduced apoptosis. In contrast, the striatum of acute URB597-treated rats showed an increased number of subventricular proliferative, astroglial and apoptotic cells, which was accompanied with increased Faah expression. Main results indicated that FAAH inhibitor URB597 decreased neural proliferation, glia and apoptosis in a brain region-dependent manner, which were coupled to local changes in Faah and/or Cnr1 expression and a negative energy context.Publication Plasma Elaidic Acid Level as Biomarker of Industrial Trans Fatty Acids and Risk of Weight Change: Report from the EPIC Study(Public Library of Science (PLOS), 2015-02-12) Chajes, Veronique; Biessy, Carine; Ferrari, Pietro; Romieu, Isabelle; Freisling, Heinz; Huybrechts, Inge; Scalbert, Augustin; de Mesquita, Bas Bueno; Romaguera, Dora; Gunter, Marc J; Vineis, Paolo; Hansen, Camilla Plambeck; Jakobsen, Marianne Uhre; Clavel-Chapelon, Francoise; Fagherazzi, Guy; Boutron-Ruault, Marie-Christine; Katzke, Verana; Neamat-Allah, Jasmine; Boeing, Heiner; Bachlechner, Ursula; Trichopoulou, Antonia; Naska, Androniki; Orfanos, Philippos; Pala, Valeria; Masala, Giovanna; Mattiello, Amalia; Skeie, Guri; Weiderpass, Elisabete; Agudo, Antonio; Maria Huerta, Jose; Ardanaz, Eva; Jose Sanchez, Maria; Dorronsoro, Miren; Ramon Quiros, Jose; Johansson, Ingegerd; Winkvist, Anna; Sonested, Emily; Key, Tim; Khaw, Kay-Tee; Wareham, Nicolas J.; Peeters, Petra H. M.; Slimani, NadiaBackground: Few epidemiological studies have examined the association between dietary trans fatty acids and weight gain, and the evidence remains inconsistent. The main objective of the study was to investigate the prospective association between biomarker of industrial trans fatty acids and change in weight within the large study European Prospective Investigation into Cancer and Nutrition ( EPIC) cohort. Methods: Baseline plasma fatty acid concentrations were determined in a representative EPIC sample from the 23 participating EPIC centers. A total of 1,945 individuals were followed for a median of 4.9 years to monitor weight change. The association between elaidic acid level and percent change of weight was investigated using a multinomial logistic regression model, adjusted by length of follow- up, age, energy, alcohol, smoking status, physical activity, and region. Results: In women, doubling elaidic acid was associated with a decreased risk of weight loss ( odds ratio ( OR) = 0.69, 95% confidence interval ( CI) = 0.55- 0.88, p = 0.002) and a trend was observed with an increased risk of weight gain during the 5- year follow- up ( OR = 1.23, 95% CI = 0.97- 1.56, p = 0.082) ( p- trend<. 0001). In men, a trend was observed for doubling elaidic acid level and risk of weight loss ( OR = 0.82, 95% CI = 0.66- 1.01, p = 0.062) while no significant association was found with risk of weight gain during the 5- year follow- up ( OR = 1.08, 95% CI = 0.88- 1.33, p = 0.454). No association was found for saturated and cismonounsaturated fatty acids. Conclusions: These data suggest that a high intake of industrial trans fatty acids may decrease the risk of weight loss, particularly in women. Prevention of obesity should consider limiting the consumption of highly processed foods, the main source of industrially- produced trans fatty acids.Publication Systemic administration of oleoylethanolamide protects from neuroinflammation and anhedonia induced by LPS in rats.(Oxford University Press, 2015-04) Sayd, Aline; Antón, María; Alén, Francisco; Caso, Javier Rubén; Pavón, Francisco-Javier; Leza, Juan Carlos; Rodríguez de Fonseca, Fernando; García-Bueno, Borja; Orio, Laura; [Anton,M; Alen,F; Rodríguez de Fonseca,F; Orio,L] Department of Psychobiology, Faculty of Psychology, Complutense University, Complutense University of Madrid (UCM), Madrid, Spain. [Said,A; Lez,JC; Garcia-Bueno,B] Department of Pharmacology, Faculty of Medicine, UCM, and Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM)), Madrid, Spain . [Caso,JR] Department of Psychiatry, Faculty of Medicine, UCM, and Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid, Spain. [Pavón,J; Rodriguez de Fonseca,F] UGC Salud Mental. Instituto de Investigación Biomédica de Málaga. Hospital Regional Universitario de Málaga.Universidad de Málaga. Red de Trastornos Adictivos, Málaga, Spain.BACKGROUND: The acylethanolamides oleoylethanolamide and palmitoylethanolamide are endogenous lipid mediators with proposed neuroprotectant properties in central nervous system (CNS) pathologies. The precise mechanisms remain partly unknown, but growing evidence suggests an antiinflammatory/antioxidant profile. METHODS: We tested whether oleoylethanolamide/palmitoylethanolamide (10 mg/kg, i.p.) attenuate neuroinflammation and acute phase responses (hypothalamus-pituitary-adrenal (HPA) stress axis stress axis activation, thermoregulation, and anhedonia) induced by lipopolysaccharide (0.5 mg/kg, i.p.) in rats. RESULTS: Lipopolysaccharide increased mRNA levels of the proinflammatory cytokines tumor necrosis factor-α, interleukin-1β, and interleukin-6, nuclear transcription factor-κB activity, and the expression of its inhibitory protein IκBα in cytoplasm, the inducible isoforms of nitric oxide synthase and cyclooxygenase-2, microsomal prostaglandin E2 synthase mRNA, and proinflammatory prostaglandin E2 content in frontal cortex 150 minutes after administration. As a result, the markers of nitrosative/oxidative stress nitrites (NO2(-)) and malondialdehyde were increased. Pretreatment with oleoylethanolamide/ palmitoylethanolamide reduced plasma tumor necrosis factor-α levels after lipopolysaccharide, but only oleoylethanolamide significantly reduced brain tumor necrosis factor-α mRNA. Oleoylethanolamide and palmitoylethanolamide prevented lipopolysaccharide-induced nuclear transcription factor-κB (NF-κB)/IκBα upregulation in nuclear and cytosolic extracts, respectively, the expression of inducible isoforms of nitric oxide synthase, cyclooxygenase-2, and microsomal prostaglandin E2 synthase and the levels of prostaglandin E2. Additionally, both acylethanolamides reduced lipopolysaccharide-induced oxidative/nitrosative stress. Neither oleoylethanolamide nor palmitoylethanolamide modified plasma corticosterone levels after lipopolysaccharide, but both acylethanolamides reduced the expression of hypothalamic markers of thermoregulation interleukin-1β, cyclooxygenase-2, and prostaglandin E2, and potentiated the hypothermic response after lipopolysaccharide. Interestingly, only oleoylethanolamide disrupted lipopolysaccharide-induced anhedonia in a saccharine preference test. CONCLUSIONS: Results indicate that oleoylethanolamide and palmitoylethanolamide have antiinflammatory/neuroprotective properties and suggest a role for these acylethanolamides as modulators of CNS pathologies with a neuroinflammatory component.Publication Treatment with a novel oleic-acid-dihydroxyamphetamine conjugation ameliorates non-alcoholic fatty liver disease in obese Zucker rats.(Company of Biologists, 2015-10-01) Decara, Juan M; Pavón, Francisco Javier; Suárez, Juan; Romero-Cuevas, Miguel; Baixeras, Elena; Vázquez, Mariam; Rivera, Patricia; Gavito, Ana L; Almeida, Bruno; Joglar, Jesús; de la Torre, Rafael; Rodríguez de Fonseca, Fernando; Serrano, Antonia; [Decara,JM; Pavón FJ; Suárez,J; Romero-Cuevas,M; Baixeras,E; Vázquez,M; Rivera,P; Gavito,AL; Rodríguez de Fonseca,F; Serrano A] Unidad Gestión Clínica de Salud Mental, Instituto de Investigación Biomédica de Málaga (IBIMA), Hospital Regional Universitario de Málaga/Universidad de Málaga, Málaga, Spain. [Pavón,FJ; Suárez,J; Romero-Cuevas,M; de la Torre,R; Rodríguez de Fonseca,F; Serrano,A] CIBER de Fisiopatología de la Obesidad y la Nutrición (CIBERobn), Instituto de Salud Carlos III (ISCIII), Madrid, Spain. [Almeida,B; de la Torre,R] Institut Hospital del Mar d'Investigacions Mèdiques (IMIM), Neurosciences Program, Barcelona, Spain. Facultat de Ciencies de la Salut i de la Vida, Universitat Pompeu Fabra (CEXS-UPF), Barcelona, Spain. [Joglar,J] Departamento de Química Biológica y Modelización Molecular, Instituto de Química Avanzada de Cataluña (IQAC-CSIC), Barcelona, Spain.Fatty liver disease is one of the main hepatic complications associated with obesity. To date, there are no effective treatments for this pathology apart from the use of classical fibrates. In this study, we have characterized the in vivo effects of a novel conjugation of oleic acid with an amphetamine derivative (OLHHA) in an animal model of genetic obesity. Lean and obese Zucker rats received a daily intraperitoneal administration of OLHHA (5 mg kg(-1)) for 15 days. Plasma and liver samples were collected for the biochemical and molecular biological analyses, including both immunohistochemical and histological studies. The expression of key enzymes and proteins that are involved in lipid metabolism and energy homeostasis was evaluated in the liver samples. The potential of OLHHA to produce adverse drug reactions or toxicity was also evaluated through the monitoring of interactions with hERG channel and liver cytochrome. We found that OLHHA is a drug with a safe pharmacological profile. Treatment for 15 days with OLHHA reduced the liver fat content and plasma triglyceride levels, and this was accompanied by a general improvement in the profile of plasma parameters related to liver damage in the obese rats. A decrease in fat accumulation in the liver was confirmed using histological staining. Additionally, OLHHA was observed to exert anti-apoptotic effects. This hepatoprotective activity in obese rats was associated with an increase in the mRNA and protein expression of the cannabinoid type 1 receptor and a decrease in the expression of the lipogenic enzymes FAS and HMGCR primarily. However, changes in the mRNA expression of certain proteins were not associated with changes in the protein expression (i.e. L-FABP and INSIG2). The present results demonstrate that OLHHA is a potential anti-steatotic drug that ameliorates the obesity-associated fatty liver and suggest the potential use of this new drug for the treatment of non-alcoholic fatty liver disease.