Examinando por Autor "Alguacil, Luis F."

Mostrando 1 - 6 de 6

Clusterin levels in undernourished SH-SY5Y cells
(2021-05-04) Rodríguez-Rivera, Carmen; Pérez-Carrión, María Dolores; Casariego Olavarría, Lucía; Alguacil, Luis F.; Polanco Mora, María José; Gonzalez-Martín, Carmen
Food-related disorders are increasingly common in developed societies, and the psychological component of these disorders has been gaining increasing attention. Both overnourishment with high-fat diets and perinatal undernourishment in mice have been linked to a higher motivation toward food, resulting in an alteration in food intake. Clusterin (CLU), a multifaced protein, is overexpressed in the nucleus accumbens (NAc) of overfed rats, as well as in those that suffered chronic undernutrition. Moreover, an increase of this protein was observed in the plasma of obese patients with food addiction, suggesting the implication of CLU in this eating disorder. To characterize CLU’s cellular mechanisms, in vitro experiments of undernutrition were performed using dopaminergic SH-SY5Y cells. To mimic in vivo dietary conditions, cells were treated with different fetal bovine serum (FBS) concentrations, resulting in control (C group) diet (10% FBS), undernourishment (U group) diet (0.5% FBS), and undernourishment diet followed by restoration of control diet (UC group) (0.5 + 10% FBS). Undernourishment compromised cell viability and proliferation, and concomitantly increased CLU secretion as well as the cytosolic pool of the protein, while decreasing the mitochondrial level. The restoration of normal conditions tended to recover cell physiology, and the normal levels and distribution of CLU. This research study is a step forward toward the characterization of clusterin as a potential marker for food addiction and nutritional status.
Clusterin overexpression as a potential neuroprotective response to the pathological effects of high fat dieting on the brain reward system
(Elsevier, 2021-04-07) Rodríguez-Rivera, Carmen; Pérez-Ortiz, Jose Manuel; Pook, Elizabeth; Conjaerts, Nina; Alguacil, Luis F.; Gonzalez-Martín, Carmen
High-fat diets (HFDs) can lead to pathological changes in the brain underlying several behavioral disturbances (e. g., reward deficiency). To further increase our knowledge of these associations, we studied the sucrose reward and the brain expression of clusterin, a protein that is overexpressed after several kind of brain damaging conditions. C57BL/6J male mice were differentially fed on an HFD or standard chow for 41 days and underwent 11 sucrose place conditioning sessions followed by 4 extinction sessions to monitor the effects of HFD on sucrose reward by means of free choice tests. We quantified clusterin expression by immunochemistry in the nucleus accumbens, dorsal striatum and cingulate cortex. HFD tended to provoke a transient potentiation in the acquisition of sucrose-conditioned place preference, but this effect was followed by a much more consistent reduction in sucrose preference, which spontaneously disappeared after 31 days of an HFD with no need for extinction learning. The HFD mice showed higher clusterin expression in the nucleus accumbens but not in the other brain areas studied. The results confirm that HFDs strongly influence the rewarding properties of palatable foods and suggest a direct connection with neurotoxic alterations in the brain reward system tagged by clusterin overexpression.
Perinatal undernourishment provokes long-lasting alterations of clusterin and fumarate hydratase expression in the rat nucleus accumbens
(Taylor and Francis, 2021-03-23) Rodríguez-Rivera, Carmen; Gonzalez-Martín, Carmen; Fernández-Millán, Elisa; Álvarez, Carmen; Escrivá, Fernando; Alguacil, Luis F.
Background: Background: Perinatal malnutrition seems to provoke important neurochemical alterations in the brain that lead to higher vulnerability to develop neuropsychiatric disorders in the adulthood. Objectives: We have examined the persistence and reversibility of the changes induced by perinatal undernourishment on the expression of fumarate hydratase in the rat nucleus accumbens, bearing in mind that this expression has been previously linked with addictive disorders. Clusterin, a multifunctional protein known to be neuroprotective and possibly related to addiction in humans, was studied in parallel. Methods: Female Wistar rats underwent a severe restriction of food during gestation and lactation. Upon weaning, a subgroup of undernourished animals was switched to normal chow and another one continued under food restriction. Control rats and their mothers were fed on chow along the experiment. Fumarate hydratase and clusterin were quantified by western blot after five months of postnatal life in the three experimental groups. Results: Food restriction along the whole experimental period provoked a marked upregulation of both clusterin and fumarate hydratase in the mitochondrial fraction of the nucleus accumbens. In the case of clusterin, this upregulation was also observed in the cytosolic fraction of the nucleus accumbens. When undernourishment was limited to gestation and lactation the two proteins appeared downregulated with respect to controls. Conclusion: The results are consistent with the idea that perinatal malnutrition provokes marked changes in brain neurochemistry that are not fully corrected by the rehabilitation of normal feeding and could be linked to behavioural disturbances in the adulthood, that is, increased vulnerability to addiction.
Proteomic Identification of Biomarkers Associated with Eating Control and Bariatric Surgery Outcomes in Patients with Morbid Obesity
(Springer, 2018-11-13) Rodríguez-Rivera, Carmen; Pérez-García, Carmen; Muñóz-Rodríguez, José Ramón; Vicente-Rodríguez, Marta; Polo, Filomena; Ford, Rhian-Marie; Segura, Esperanza; León, Alberto; Salas, Elisabet; Sáenz-Mateos, Luis; Gonzalez-Martín, Carmen; Herradón, Gonzalo; Beato-Fernández, Luis; Martín-Fernández, Jesús; Alguacil, Luis F.
Background The current therapeutics of morbid obesity could be significantly improved after the identification of novel biomarkers associated with the food addiction endophenotype of obesity and with bariatric surgery outcomes. Methods We applied differential expression proteomics and enzyme-linked immunosorbent confirmatory assays to identify (a) proteins that varied according to loss of control over eating in morbidly obese patients and (b) proteins that varied between normoweight controls and patients before and 1 year after bariatric surgery. Results Clusterin was the only protein that consistently varied according to eating control in patients. Patients showed increased levels of serum amyloid P protein, apolipoprotein A4, serotransferrin, complement factors B and C3 and haptoglobin with respect to controls; the levels of all these proteins tended to return to control values 1 year after surgery. In contrast, apolipoprotein A1 and transthyretin were initially downregulated in patients and were scarcely changed by surgery. Leucine-rich alpha-2-glycoprotein was markedly increased in patients only after surgery. Conclusions Clusterin could be of interest as a putative biomarker for food addiction diagnosis in people with morbid obesity. In addition, postsurgical normalization of the proteins initially dysregulated in obese subjects might help monitor clinical improvements after surgery, while lasting or newly detected alterations (i.e., those affecting transthyretin and leucine-rich alpha-2-glycoprotein) could reflect partial refractoriness and/or contribute to the early prediction of clinical problems.
Sciatic Nerve Ligation Downregulates Mitochondrial Clusterin in the Rat Prefrontal Cortex
(2020) Rodríguez-Rivera, Carmen; Girón, Rocío; Sánchez-Robles, Eva; Gonzalez-Martín, Carmen; Goicoechea, Carlos; Alguacil, Luis F.
—The concentration of the multifunctional protein clusterin is reduced in the plasma of subjects with degenerative scoliosis (DS) and carpal tunnel syndrome (CTS) but elevated in the cerebrospinal fluid of neuropathic pain patients successfully treated with spinal cord stimulation. The present work tries to increase the knowledge of pain-associated changes of plasma and brain clusterin by using an animal model of neuropathy. We studied the effects of sciatic nerve ligation on mechanical allodynia (von Frey test), anxiety (elevated plus maze test), plasma clusterin (enzyme-linked immunosorbent assay) and clusterin expression in the nucleus accumbens (NAC) and prefrontal cortex (PFC) of adult male Wistar rats (western blot). The possible modulatory role of high fat (HF) dieting was also studied, bearing in mind that obesity has been also reported to influence nociception, clusterin levels and prefrontal cortex activation. Animals with nerve ligation showed mechanical allodynia, anxiety and a marked downregulation of clusterin in the mitochondrial fraction of the prefrontal cortex. Animals fed on HF also exhibited a slight increase of the sensitivity to mechanical stimuli and anxiety; however, the diet did not potentiate the effects of nerve ligation. The results did not confirm a parallelism between neuropathy, obesity and alterations of plasma levels of clusterin, but strongly suggest that the protein could be involved in the functional reorganization of the prefrontal cortex which has been recently reported in chronic pain conditions. 2020 IBRO. Published by Elsevier Ltd. All rights reserved.
Undernutrition induces major alterations in the lipid droplets of white and brown adipose tissues in wistar rats
(Elsevier, 2021-02-21) Rodríguez-Rivera, Carmen; Santín Moreda, Laura; Alguacil, Luis F.; Escrivá, Fernando; Álvarez, Carmen; Gonzalez-Martín, Carmen
Several studies have shown a relationship between the distribution of fat mass around the organism, metabolic disorders, and an increased risk of morbidity and mortality. It has been demonstrated that in obese animals there is a big rise in the white fat deposits due to hyperplasia and hypertrophy of the adipocytes. Studies related to weight and health have been more popular regarding obesity rather than extreme caquexia or calorico-proteic deficiencies, but these states are interesting from the point of view of the preferential atrophy of certain organs that may help us in the understanding of undernourishment. Moreover, the discovery of beige adipose tissue has instigated thoughts around the roles played by the different cells in the adipose tissue as well as its adaptability in pathological states. In our study we carried out morphometric, morphological, and quantitative measurements of the adipose tissue in an animal model based on a 40− 50% diet restriction in comparison to control animals. We have found a decrease in the size of white adipocytes together with a variation in the lipid droplet size of brown adipocytes in undernourished animals, what may be considered as possible transformations between the types of adipose tissues, and that could be caused by an adaptive phenomenon to the undernourished state.