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Lage R.,University of Santiago de Compostela | Lage R.,CIBER ISCIII | Lage R.,University of Barcelona | Parisi C.,University of Santiago de Compostela | And 16 more authors.
International Journal of Neuropsychopharmacology | Year: 2015

Background: Cumulative data indicate that the endocannabinoid system plays a major role in feeding behavior and energy balance. Genetic silencing of cannabinoid receptor type 1 (CB1) reduces body weight gain, independently of food intake. Methods: In this work, we investigated whether the hypothalamic neuropeptide expression pattern supports the absence of the anorexigenic response observed under constitutive CB1 ablation, by using neuronal CB1 conditional null mice (CamK-CB1-KO) and whole body CB1 null mice (CB1-KO). Results: Our data showed that both CB1 null models display a marked decrease in proopiomelanocortin (POMC) and cocaineamphetamine-regulated transcript (CART) expression in the arcuate nucleus of the hypothalamus (ARC). Conclusions: This evidence suggests that a lack of hypophagia is associated with the suppression of ARC anorexigenic neuropeptides and that behavioral changes in food intake (or lack thereof) after constitutive CB1 ablation are likely mediated by impaired melanocortin and CART signaling in the hypothalamus. © The Author 2015.

Folgueira C.,Complexo Hospitalario Universitario Of Santiago Chus Sergas | Folgueira C.,CIBER ISCIII | Seoane L.M.,Complexo Hospitalario Universitario Of Santiago Chus Sergas | Seoane L.M.,CIBER ISCIII | And 2 more authors.
Frontiers of Hormone Research | Year: 2014

The stomach-brain connection has been revealed to be one of the most promising targets in treating obesity. The stomach plays a key role in the homeostatic mechanism implicating stomach-brain communication regulated under neural and hormonal control. The present review explores specific topics related to gut-brain interactions focus on the stomach-brain connection through the different known systems implied in energy balance control as ghrelin, and nesfatin. Moreover, novel mechanisms for energy balance regulation involving gastric-brain communication are described including the role of the gastric intracellular mTOR/S6K1 pathway mediating the interaction among ghrelin, nesfatin and endocannabinoid gastric systems to modulate metabolism. © 2014 S. Karger AG, Basel.

Pardo M.,Complexo Hospitalario Universitario Of Santiago Chus Sergas | Pardo M.,CIBER ISCIII | Roca-Rivada A.,Complexo Hospitalario Universitario Of Santiago Chus Sergas | Roca-Rivada A.,CIBER ISCIII | And 4 more authors.
Endocrine | Year: 2012

Obesity is presently reaching pandemic proportions and it is becoming a major health concern in developed and developing countries due to its comorbidities like type II diabetes, cardiovascular pathologies, and some cancers. The discovery of the adipose tissue role as an endocrine gland able to secrete adipokines that affects whole-body energy homeostasis has become a key break-through toward a better molecular understanding of obesity. Among the known adipokines involved in the regulation of energy metabolism very few have been clearly seen as central regulators of insulin sensitivity, metabolism, and energy homeostasis. Thus, the discovery and characterization of new adipocyte-derived factors is still in progress. Proteomics technology has emerged as a useful tool to analyze adipose tissue secretion (secretome) dynamics giving awider picture into themolecular events that control body weight. Besides the identification of new secreted proteins, the advantage of using this approach is the possibility to detect post-translational modifications and protein interactions that generally cannot be predicted by genome studies. In this review, we summarize the recent efforts to identify new bioactive adipokines by proteomics especially in pathological situations such as obesity. © Springer Science+Business Media, LLC 2012.

Senin L.L.,Complexo Hospitalario Universitario Of Santiago Chus Sergas | Senin L.L.,CIBER ISCIII | Roca-Rivada A.,CIBER ISCIII | Roca-Rivada A.,Complexo Hospitalario Universitario Of Santiago Chus Sergas | And 14 more authors.
Journal of Proteomics | Year: 2015

Obesity is a major public health threat for many industrialised countries. Bariatric surgery is the most effective treatment against obesity, suggesting that gut derived signals are crucial for energy balance regulation. Several descriptive studies have proven the presence of gastric endogenous systems that modulate energy homeostasis; however, these systems and the interactions between them are still not well known. In the present study, we show for the first time the comparative 2-DE gastric secretome analysis under different nutritional status. We have identified 38 differently secreted proteins by comparing stomach secretomes from tissue explant cultures of rats under feeding, fasting and re-feeding conditions. Among the proteins identified, glyceraldehyde-3-phosphate dehydrogenase was found to be more abundant in gastric secretome and plasma after re-feeding, and downregulated in obesity. Additionally, two calponin-1 species were decreased in feeding state, and other were modulated by nutritional and metabolic conditions. These and other secreted proteins identified in this work may be considered as potential gastrokines implicated in food intake regulation. Biological significance: The present work has an important impact in the field of obesity, especially in the regulation of body weight maintenance by the stomach. Nowadays, the most effective treatment in the fight against obesity is bariatric surgery, which suggests that stomach derived signals might be crucial for the regulation of the energy homeostasis. However, until now, the knowledge about the gastrokines and its mechanism of action has been poorly elucidated. In the present work, we had updated a previously validated explant secretion model for proteomic studies; this analysis allowed us, for the first time, to study the gastric secretome without interferences from other organs. We had identified 38 differently secreted proteins comparing ex vivo cultured stomachs from rats under feeding, fasting and re-feeding regimes. The results in the present article provide novel targets to study the role of the stomach in body weight and appetite regulation, and suggest new potential therapeutic targets for treating obesity. © 2015 Elsevier B.V.

Roca-Rivada A.,Complexo Hospitalario Universitario Of Santiago Chus Sergas | Roca-Rivada A.,CIBER ISCIII | Al-Massadi O.,Complexo Hospitalario Universitario Of Santiago Chus Sergas | Al-Massadi O.,CIBER ISCIII | And 11 more authors.
Journal of Proteomics | Year: 2012

The notion that skeletal muscle is a secretory organ capable to release proteins that can act locally in an autocrine/paracrine manner or even in an endocrine manner to communicate with distant tissues has now been recognized. Under this context, a new paradigm has arisen implicating the muscle in metabolism regulation. Considering the evidences that give exercise a protective role against illnesses associated to physical inactivity, it becomes of especial relevance to characterize muscle secreted proteins. In the present study we show for the first time the secretome characterization and the comparative 2-DE secretome analysis among fast-glycolytic (gastrocnemius) and slow-oxidative (soleus) rat muscle explants and its variation after exercise intervention. We have identified 19 differently secreted proteins when comparing soleus and gastrocnemius secretomes, and 10 in gastrocnemius and 17 in soleus distinctive secreted proteins after 1. week of endurance exercise training. Among identified proteins, DJ-1 was found to be more abundant in fast-glycolytic fiber secretomes. On the contrary, FABP-3 was elevated in slow-oxidative fiber secretomes, although its secretion from gastrocnemius muscle increased in exercised animals. These and other secreted proteins identified in this work may be considered as potential myokines. © 2012 Elsevier B.V.

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