González Martín, Carmen

Background: The outcomes of bariatric surgery are very irregular and mostly unpredictable. The search for variables of predictive value is encouraged to help preventing therapeutic failures. Objective: We aimed to confirm the hypothesis that preexisting eating behaviors could predict neuroendocrine and metabolic outcomes of gastric bypass surgery in morbidly obese subjects. Methods: Twenty-one morbidly obese patients from the Bariatric Surgery Program of our hospital were selected according to the specific inclusion and exclusion criteria for this study. The subjects filled out a validated questionnaire to quantify the "loss-of-control" (LC) dimension of food craving and provided serum samples at the onset of the study and 1 year after gastric bypass surgery. Hematological, metabolic, and hormonal variables were studied by conventional clinical tests and enzyme immunoassays and checked for correlations with LC both before and after surgery. Results: Those patients that had exhibited worse eating control at the beginning of the study experienced a better metabolic response 1 year after surgery in terms of reduction of serum insulin, HOMA1-IR, HOMA2-IR, and vitamin D1; all these variables were inversely correlated with presurgical LC. Serum brain-derived neurotrophic factor (BDNF) levels showed the same tendency; in fact, BDNF significantly decreased only in those patients with worse eating control. Conclusions: Problematic eating behaviors may predict a better response of insulin resistance and a specific reduction of serum BDNF in morbidly obese patients after gastric bypass surgery.

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.

Background: The outcomes of bariatric surgery are very irregular and mostly unpredictable. The search for variables of predictive value is encouraged to help preventing therapeutic failures. Objective: We aimed to confirm the hypothesis that preexisting eating behaviors could predict neuroendocrine and metabolic outcomes of gastric bypass surgery in morbidly obese subjects. Methods: Twenty-one morbidly obese patients from the Bariatric Surgery Program of our hospital were selected according to the specific inclusion and exclusion criteria for this study. The subjects filled out a validated questionnaire to quantify the "loss-of-control" (LC) dimension of food craving and provided serum samples at the onset of the study and 1 year after gastric bypass surgery. Hematological, metabolic, and hormonal variables were studied by conventional clinical tests and enzyme immunoassays and checked for correlations with LC both before and after surgery. Results: Those patients that had exhibited worse eating control at the beginning of the study experienced a better metabolic response 1 year after surgery in terms of reduction of serum insulin, HOMA1-IR, HOMA2-IR, and vitamin D1; all these variables were inversely correlated with presurgical LC. Serum brain-derived neurotrophic factor (BDNF) levels showed the same tendency; in fact, BDNF significantly decreased only in those patients with worse eating control. Conclusions: Problematic eating behaviors may predict a better response of insulin resistance and a specific reduction of serum BDNF in morbidly obese patients after gastric bypass surgery.

Background: Preclinical work revealed significant interactions between ligands of the histamine H3 receptor and different drugs of abuse. In the case of psychostimulants, the results reported are somewhat controversial and human data are still scarce, despite the fact that an inverse agonist of the H3 receptor (pitolisant) has reached the market after approval for the treatment of narcolepsy. Aims: We have studied associations between histamine H3 receptor gene variants and cocaine use disorder to increase the knowledge of the possible involvement of histamine H3 receptor in drug abuse. Methods: Seven single nucleotide polymorphisms of the histamine H3 receptor gene were genotyped by using a multiplexing assay in 248 samples of subjects with cocaine use disorder and 500 randomized samples of subjects representative of the Spanish population. Results: The study of the epidemiological information associated to the samples revealed that subjects with cocaine use disorder broadly abused alcohol, tobacco and cannabinoids. Two single nucleotide polymorphisms (rs3787430 and rs74627870) were found significantly associated with the occurrence of addiction and one more (rs13042865) was specifically related to the severity of cocaine dependence within drug abusers. Conclusions: The associations found in this study further extend the hypothesis that histamine H3 receptor function could be relevant in drug abuse in general and cocaine addiction in particular.

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.

Dietary treatment with high-fat diets (HFD) triggeenrs diabetes and hyperleptinemia, con- comitantly with a partial state of leptin resistance that affects hepatic and adipose tissue but not the heart. In this context, characterized by widespread steatosis, cardiac lipid con- tent remains unchanged. As previously reported, HFD-evoked hyperleptinemia could be a pivotal element contributing to increase fatty-acid (FA) metabolism in the heart and to prevent cardiac steatosis. This metabolic adaptation might theoretically reduce energy efficiency in cardiomyocytes and lead to cardiac electrophysiological remodeling. There- fore the aim of the current study has been to investigate the impact of long-term HFD on cardiac metabolism and electrophysiological properties of the principal ionic currents responsible of the action potential duration in mouse cardiomyocytes. Male C57BL/6J mice were fed a control (10 kcal% from fat) or HFD (45 kcal% from fat) during 32 weeks. Quantification of enzymatic activities regulating mitochondrial uptake of pyruvate and FA showed an increase of both carnitine-palmitoyltransferase and citrate synthase activities together with a decrease of lactate dehydrogenase and pyruvate dehydrogenase activities. Increased expression of uncoupling protein-3, Mn-, and Cu/Zn-superoxide dismutases and catalase were also detected. Total glutathione/oxidized glutathione ratios were unaffected by HFD. These data suggest that HFD triggers adaptive mechanisms aimed at facilitating FA catabolism, and preventing oxidative stress. All these changes did not affect the dura- tion of action potentials in cardiomyocytes and only slightly modified electrocardiographic parameters.

Desde el punto de vista etimológico, el término “tóxico” deriva de la palabra griega toxikon que significa flecha envenenada (referido a las toxinas aplicadas en su punta). Así lo utiliza Homero en La Iliada y en la Odisea. Toxikon, junto a logos (conocimiento) conforman la raíz de la palabra “Toxicología”, que viene por tanto a significar “ciencia de los venenos”. Durante mucho tiempo veneno y tóxico fueron sinónimos y no se diferenciaron hasta el siglo XIX cuando la Toxicología paso a definirse como “la ciencia que se ocupa del estudio de las sustancias tóxicas”, siendo sólo “veneno” aquella sustancia que se utiliza con la intención de matar.