Publications by authors named "Rubén Tovar"

10 Publications

  • Page 1 of 1

Palmitoleoylethanolamide Is an Efficient Anti-Obesity Endogenous Compound: Comparison with Oleylethanolamide in Diet-Induced Obesity.

Nutrients 2021 Jul 28;13(8). Epub 2021 Jul 28.

Instituto de Investigación Biomédica de Málaga (IBIMA), Hospital Universitario Regional de Málaga, UGC Salud Mental, Avda. Carlos Haya 82, Pabellón de Gobierno, 29010 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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/nu13082589DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8400335PMC
July 2021

Comparative development and ocular histology between epigean and subterranean salamanders () from central Texas.

PeerJ 2021 28;9:e11840. Epub 2021 Jul 28.

Department of Biology, Texas State University, San Marcos, TX, United States of America.

The salamander clade from the karst regions of central Texas provides an ideal platform for comparing divergent nervous and sensory systems since some species exhibit extreme phenotypes thought to be associated with inhabiting a subterranean environment, including highly reduced eyes, while others retain an ancestral ocular phenotype appropriate for life above ground. We describe ocular morphology, comparing three salamander species representing two phenotypes-the surface-dwelling Barton Springs salamander () and San Marcos salamander () and the obligate subterranean Texas blind salamander () - in terms of structure and size of their eyes. Eyes were examined using confocal microscopy and measurements were made using ImageJ. Statistical analysis of data was carried out using R. We also provide a developmental series and track eye development and immunolocalization of Pax6 in and . Adult histology of the surface-dwelling San Marcos salamander () shows similarities to . The eyes of adults of the epigean species and appear fully developed with all the histological features of a fully functional eye. In contrast, the eyes of adults have fewer layers, lack lenses and other features associated with vision as has been reported previously. However, in early developmental stages eye morphology did not differ significantly between and . Parallel development is observed between the two phenotypes in terms of morphology; however, Pax6 labeling seems to decrease in the latter stages of development in E.. We test for immunolabeling of the visual pigment proteins opsin and rhodopsin and observe immunolocalization around photoreceptor disks in and , but not in the subterranean . Our results from examining developing salamanders suggest a combination of underdevelopment and degeneration contribute to the reduced eyes of adult .
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.7717/peerj.11840DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8325428PMC
July 2021

Activation of PI3K/Akt Signaling Pathway in Rat Hypothalamus Induced by an Acute Oral Administration of D-Pinitol.

Nutrients 2021 Jun 30;13(7). Epub 2021 Jun 30.

Instituto de Investigación Biomédica de Málaga (IBIMA), Hospital Universitario Regional de Málaga, UGC Salud Mental, Avda. Carlos Haya 82, Pabellón de Gobierno, 29010 Málaga, Spain.

D-Pinitol (DPIN) is a natural occurring inositol capable of activating the insulin pathway in peripheral tissues, whereas this has not been thoroughly studied in the central nervous system. The present study assessed the potential regulatory effects of DPIN on the hypothalamic insulin signaling pathway. To this end we investigated the Phosphatidylinositol-3-kinase (PI3K)/Protein Kinase B (Akt) signaling cascade in a rat model following oral administration of DPIN. The PI3K/Akt-associated proteins were quantified by Western blot in terms of phosphorylation and total expression. Results indicate that the acute administration of DPIN induced time-dependent phosphorylation of PI3K/Akt and its related substrates within the hypothalamus, indicating an activation of the insulin signaling pathway. This profile is consistent with DPIN as an insulin sensitizer since we also found a decrease in the circulating concentration of this hormone. Overall, the present study shows the pharmacological action of DPIN in the hypothalamus through the PI3K/Akt pathway when giving in fasted animals. These findings suggest that DPIN might be a candidate to treat brain insulin-resistance associated disorders by activating insulin response beyond the insulin receptor.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/nu13072268DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8308282PMC
June 2021

Analysis of Both Lipid Metabolism and Endocannabinoid Signaling Reveals a New Role for Hypothalamic Astrocytes in Maternal Caloric Restriction-Induced Perinatal Programming.

Int J Mol Sci 2021 Jun 11;22(12). Epub 2021 Jun 11.

Instituto de Investigación Biomédica de Málaga-IBIMA, 29010 Málaga, Spain.

Maternal malnutrition in critical periods of development increases the risk of developing short- and long-term diseases in the offspring. The alterations induced by this nutritional programming in the hypothalamus of the offspring are of special relevance due to its role in energy homeostasis, especially in the endocannabinoid system (ECS), which is involved in metabolic functions. Since astrocytes are essential for neuronal energy efficiency and are implicated in brain endocannabinoid signaling, here we have used a rat model to investigate whether a moderate caloric restriction (R) spanning from two weeks prior to the start of gestation to its end induced changes in offspring hypothalamic (a) ECS, (b) lipid metabolism (LM) and/or (c) hypothalamic astrocytes. Monitorization was performed by analyzing both the gene and protein expression of proteins involved in LM and ECS signaling. Offspring born from caloric-restricted mothers presented hypothalamic alterations in both the main enzymes involved in LM and endocannabinoids synthesis/degradation. Furthermore, most of these changes were similar to those observed in hypothalamic offspring astrocytes in culture. In conclusion, a maternal low caloric intake altered LM and ECS in both the hypothalamus and its astrocytes, pointing to these glial cells as responsible for a large part of the alterations seen in the total hypothalamus and suggesting a high degree of involvement of astrocytes in nutritional programming.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/ijms22126292DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8230792PMC
June 2021

Recombinant IGF-1 Induces Sex-Specific Changes in Bone Composition and Remodeling in Adult Mice with Deficiency.

Int J Mol Sci 2021 Apr 14;22(8). Epub 2021 Apr 14.

Departamento de Anatomía Humana, Medicina Legal e Historia de la Ciencia, Instituto de Investigación Biomédica de Málaga (IBIMA), Universidad de Málaga, 29071 Málaga, Spain.

Deficiency of pregnancy-associated plasma protein-A2 (PAPP-A2), an IGF-1 availability regulator, causes postnatal growth failure and dysregulation of bone size and density. The present study aimed to determine the effects of recombinant murine IGF-1 (rmIGF-1) on bone composition and remodeling in constitutive knock-out (ko/ko) mice. To address this challenge, X-ray diffraction (XRD), attenuated total reflection-fourier transform infra-red (ATR-FTIR) spectroscopy and gene expression analysis of members of the IGF-1 system and bone resorption/formation were performed. mice (both sexes) had reduced body and bone length. Male mice had specific alterations in bone composition (mineral-to-matrix ratio, carbonate substitution and mineral crystallinity), but not in bone remodeling. In contrast, decreases in collagen maturity and increases in , (resorption) and (formation) characterized the bone of females. A single rmIGF-1 administration (0.3 mg/kg) induced short-term changes in bone composition in mice (both sexes). rmIGF-1 treatment in females also increased collagen maturity, and , , and expression. In summary, acute IGF-1 treatment modifies bone composition and local IGF-1 response to bone remodeling in mice with deficiency. These effects depend on sex and provide important insights into potential IGF-1 therapy for growth failure and bone loss and repair.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/ijms22084048DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8070906PMC
April 2021

Maternal hypercaloric diet affects factors involved in lipid metabolism and the endogenous cannabinoid systems in the hypothalamus of adult offspring: sex-specific response of astrocytes to palmitic acid and anandamide.

Nutr Neurosci 2020 Sep 21:1-14. Epub 2020 Sep 21.

Department of Endocrinology, Fundación Investigación Biomédica del Hospital Infantil Universitario Niño Jesús, Instituto de Investigación Biomédica la Princesa, Madrid, Spain.

We aimed to investigate whether maternal malnutrition during gestation/lactation induces long-lasting changes on inflammation, lipid metabolism and endocannabinoid signaling in the adult offspring hypothalamus and the role of hypothalamic astrocytes in these changes. We analyzed the effects of a free-choice hypercaloric palatable diet (P) during (pre)gestation, lactation and/or post-weaning on inflammation, lipid metabolism and endogenous cannabinoid signaling in the adult offspring hypothalamus. We also evaluated the response of primary hypothalamic astrocytes to palmitic acid and anandamide. Postnatal exposure to a P diet induced factors involved in hypothalamic inflammation ( and ) and gliosis ( and ) in adult offspring, being more significant in females. In contrast, maternal P diet reduced factors involved in astrogliosis (), fatty acid oxidation () and monounsaturated fatty acid synthesis (). These changes were accompanied by an increase in the expression of the genes for the cannabinoid receptor () and an enzyme involved in endocannabinoid synthesis, in females and a decrease in the endocannabinoid degradation enzyme in males. These changes suggest that the maternal P diet results in sex-specific alterations in hypothalamic endocannabinoid signaling and lipid metabolism. This hypothesis was tested in hypothalamic astrocyte cultures, where palmitic acid (PA) and the polyunsaturated fatty acid N-arachidonoylethanolamine (anandamide or AEA) were found to induce similar changes in the endocannabinoid system (ECS) and lipid metabolism. These results stress the importance of both maternal diet and sex in long term metabolic programming and suggest a possible role of hypothalamic astrocytes in this process.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/1028415X.2020.1821519DOI Listing
September 2020

D-Pinitol from Is an Orally Active Natural Inositol That Reduces Pancreas Insulin Secretion and Increases Circulating Ghrelin Levels in Wistar Rats.

Nutrients 2020 Jul 8;12(7). Epub 2020 Jul 8.

Laboratorio de Medicina Regenerativa, Instituto IBIMA de Málaga, Unidad de Gestión Clínica de Salud Mental, Hospital Regional Universitario de Málaga, 29010 Málaga, Spain.

To characterize the metabolic actions of D-Pinitol, a dietary inositol, in male Wistar rats, we analyzed its oral pharmacokinetics and its effects on (a) the secretion of hormones regulating metabolism (insulin, glucagon, IGF-1, ghrelin, leptin and adiponectin), (b) insulin signaling in the liver and (c) the expression of glycolytic and neoglucogenesis enzymes. Oral D-Pinitol administration (100 or 500 mg/Kg) resulted in its rapid absorption and distribution to plasma and liver compartments. Its administration reduced insulinemia and HOMA-IR, while maintaining glycaemia thanks to increased glucagon activity. In the liver, D-Pinitol reduced the key glycolytic enzyme pyruvate kinase and decreased the phosphorylation of the enzymes AKT and GSK-3. These observations were associated with an increase in ghrelin concentrations, a known inhibitor of insulin secretion. The profile of D-Pinitol suggests its potential use as a pancreatic protector decreasing insulin secretion through ghrelin upregulation, while sustaining glycaemia through the liver-based mechanisms of glycolysis control.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/nu12072030DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7400942PMC
July 2020

Sex-Specific Anxiety and Prefrontal Cortex Glutamatergic Dysregulation Are Long-Term Consequences of Pre-and Postnatal Exposure to Hypercaloric Diet in a Rat Model.

Nutrients 2020 Jun 19;12(6). Epub 2020 Jun 19.

Hospital Regional Universitario de Málaga, Instituto de Investigación Biomédica de Málaga (IBIMA), Universidad de Málaga, 29010 Málaga, Spain.

Both maternal and early life malnutrition can cause long-term behavioral changes in the offspring, which depends on the caloric availability and the timing of the exposure. Here we investigated in a rat model whether a high-caloric palatable diet given to the mother and/or to the offspring during the perinatal and/or postnatal period might dysregulate emotional behavior and prefrontal cortex function in the offspring at adult age. To this end, we examined both anxiety responses and the mRNA/protein expression of glutamatergic, GABAergic and endocannabinoid signaling pathways in the prefrontal cortex of adult offspring. Male animals born from mothers fed the palatable diet, and who continued with this diet after weaning, exhibited anxiety associated with an overexpression of the mRNA of , and glutamate receptors in the prefrontal cortex. In addition, these animals had a reduced expression of the endocannabinoid system, the main inhibitory retrograde input to glutamate synapses, reflected in a decrease of the receptor and the enzyme. In conclusion, a hypercaloric maternal diet induces sex-dependent anxiety, associated with alterations in both glutamatergic and cannabinoid signaling in the prefrontal cortex, which are accentuated with the continuation of the palatable diet during the life of the offspring.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/nu12061829DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7353464PMC
June 2020

The adiponectin promoter activator NP-1 induces high levels of circulating TNFα and weight loss in obese (fa/fa) Zucker rats.

Sci Rep 2018 06 29;8(1):9858. Epub 2018 Jun 29.

UGC Salud Mental, Instituto de Investigación Biomédica de Málaga (IBIMA), Universidad de Málaga-Hospital Universitario Regional de Málaga, Avda. Carlos Haya 82, Pabellón de Gobierno, 29010, Málaga, Spain.

Chronic NP-1 administration reduces body weight and hepatic steatosis despite induction of tolerance in adiponectin gene transcription with respect to the acute actions of this drug. This study explored the hypothesis that NP-1 could exert these effects through mechanisms independent of adiponectin. To this aim, we took advantage of the Zucker (fa/fa) rat model, which exhibits obesity, fatty liver and elevated leptin and adiponectin levels. Body weight and food intake were reduced after chronic NP-1 treatment. Plasma TNFα concentrations were elevated but no increase in adiponectin was found. Even so, NP-1 ameliorated fatty liver and corrected dyslipidemia by mechanisms probably associated with reduced feeding, transcription of Cpt1 and down-regulation of Hmgcr-CoA expression. In brown fat tissue NP-1 increased Dnmt1 (inhibitor of Adipoq) while it reduced Ucp1 expression and heat production, which excludes thermogenesis as a mechanism of the NP-1 slimming effect. The anti-obesity action of chronic NP-1 administration might be mediated by TNFα, which is known to have anorectic actions in the hypothalamus and to regulate both Dmnt1 and Ucp1 expression in adipose tissues. This finding opens up the possibility of using NP-1-mediated TNFα-induced weight loss as an innovative treatment of complicated obesity under strict pharmacologic control.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-018-27871-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6026175PMC
June 2018

High-Resolution Molecular Typing of Trypanosoma cruzi in 2 Large Outbreaks of Acute Chagas Disease in Colombia.

J Infect Dis 2016 10 10;214(8):1252-5. Epub 2016 Aug 10.

Grupo de Investigaciones Microbiológicas-UR (GIMUR), Programa de Biología, Facultad de Ciencias Naturales y Matemáticas, Universidad el Rosario.

Oral transmission of Trypanosoma cruzi has gained relevance because of its association with high morbidity and lethality rates. This transmission route is responsible for maintaining the infection of the parasite in sylvatic cycles, and human cases have been associated mainly with the consumption of food contaminated with triatomine feces or didelphid secretions. Several ecological changes allow the intrusion of sylvatic reservoirs and triatomines to the domestic environments with subsequent food contamination. Here, high-resolution molecular tools were used to detect and genotype T. cruzi across humans, reservoirs, and insect vectors in 2 acute outbreaks of presumptive oral transmission in eastern Colombia.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/infdis/jiw360DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5034963PMC
October 2016
-->