Quintero, P. (Pablo)

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    Effects of hyperoxia exposure on metabolic markers and gene expression in 3T3- L1 adipocytes
    (Springer Verlag, 2012) Martinez, J.A. (José Alfredo); Quintero, P. (Pablo); Garcia-Diaz, D.F. (Diego F.); Gonzalez-Muniesa, P. (Pedro)
    Adipose tissue often becomes poorly oxygenated in obese subjects. This feature may provide cellular mechanisms involving chronic inflammation processes such as the release of proinflammatory cytokines and macrophage infiltration. In this context, the purpose of the present study was to determine whether a hyperoxia exposure on mature adipocytes may influence the expression of some adipokines and involve favorable changes in specific metabolic variables. 3T3-L1 adipocytes (14 days differentiated) were treated with 95% oxygen for 24 h. Cell viability, intra and extracellular reactive oxygen especies (ROS) content, glucose uptake and lactate and glycerol concentrations were measured in the culture media. Also, mRNA levels of HIF-1[alfa], leptin, IL-6, MCP-1, PPAR-[gamma], adiponectin, and ANGPTL-4 were analyzed. Hyperoxia treatment increased intra and extracellular ROS content, reduced glucose uptake and lactate release and increased glucose release. It also led to an upregulation of the expression of IL-6, MCP-1 and PPAR-[gamma], while ANGPTL4 was downregulated in the hyperoxia group with respect to control. The present data shows that hyperoxia treatment seems to provoke an inflammatory response due to the release of ROS and the upregulation of pro-inflammatory adipokines, such as IL-6 and MCP-1. On the other hand, hyperoxia may have an indirect effect on the improvement of insulin sensitivity, due to the upregulation of PPAR-[gamma] gene expression as well as a possible modulation of both glucose and lipid metabolic markers. To our knownledge, this is the first study analyzing the effect of hyperoxia in 3T3-L1 adipocytes.
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    Vitamin C modulates the interaction between adipocytes and macrophages
    (Wiley Blackwell, 2011) Martinez, J.A. (José Alfredo); Quintero, P. (Pablo); Garcia-Diaz, D.F. (Diego F.); Moreno-Aliaga, M. J. (María Jesús); Milagro-Yoldi, F.I. (Fermín Ignacio); Campión-Zabalza, J. (Javier)
    Scope: Increased adiposity is related with monocyte infiltration into the adipose tissue that accentuates inflammation. Antioxidant treatments emerge as approaches to counteract this phenomenon. Methods and results: Cocultures of differentiated 3T3-L1 adipocytes and RAW264.7 macrophages were incubated for 24-72 h with/without 100 nM insulin and/or 200 μM vitamin C (VC). Nitric oxide (NO) secretion (24 h) was measured. Also, expression (24 h) and secretion (72 h) of MCP-1, leptin and apelin were analyzed. NO secretion was significantly inhibited by insulin and VC only in cocultures. MCP-1 expression/secretion was enhanced in cocultures. Insulin incubation reduced MCP-1 expression in both cultures and VC only in controls. Both treatments inhibited MCP-1 secretion in cocultures. Apelin gene expression was induced in cocultures. Insulin induced apelin mRNA expression, but VC inhibited its expression in cocultures under insulin treatment. Apelin secretion was notably induced by insulin and inhibited by VC in cocultures. Leptin expression was decreased in coculture, while presented no effects by VC. Conclusion: VC importantly modulates the established pro-inflammatory state in the interaction between adipocytes and macrophages.
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    Estudio de los efectos metabólicos y transcriptómicos de diferentes concentraciones de oxígeno para su aplicación en la obesidad: modelos in vivo e in vitro
    (Servicio de Publicaciones de la Universidad de Navarra, 2014) Quintero, P. (Pablo); Martinez, J.A. (José Alfredo); Gonzalez-Muniesa, P. (Pedro)
    Obesity is a major public health problem that commonly leads to the initiation and development of a number of chronic diseases such as type 2 diabetes, cardiovascular diseases and different metabolic syndrome manifestations. Adipose tissue often becomes poorly oxygenated in obese subjects, and this feature may provide cellular mechanisms involving chronic inflammation processes such as the release of pro-inflammatory cytokines and macrophage infiltration. Hypoxia has been shown to reduce appetite and adipose tissue mass in humans at certain circumstances, while hyperoxia can ameliorate the hypoxic state and reduce local inflammation in some cell lines and organs. Thus, the purpose of the present study was to determine whether hypoxia and hyperoxia exposures could induce favorable changes in specific metabolic variables and gene expression pathways in both rats and 3T3-L1 adipocyte models. A cyclic hypoxia (8% O2) produced appetite suppression in rats, leading to a significant decrease in weight gain compared to control group. However, this weight reduction was accompanied by a loss of muscle mass. On the other hand, exposing rats to hyperoxia (40% O2) produced no relevant differences between groups concerning body weight and biochemical values measured after the treatment. In adipocytes exposed to 95% O2 a decrease of lactate production and an increase of glycerol release was found, along with a decrease in the expression of GLUT-1 and ANGPTL4 and an increase in PPAR-γ mRNA levels, suggesting that hyperoxia could exert a beneficial effect on the modulation of the metabolism of glucose and lipids, and may play an indirect role in improving insulin sensitivity.
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    Hypoxia a consequence of obesity and also a tool to treat excessive weight loss
    (Springer Verlag, 2015) Martinez, J.A. (José Alfredo); Quintero, P. (Pablo); Andrés, J. (Jaqueline) de; Gonzalez-Muniesa, P. (Pedro)
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    Effects of hyperoxia on oxygen-related inflammation with a focus on obesity
    (Hidawi Publishing Corporation, 2016) Martinez, J.A. (José Alfredo); Lopez-Pascual, A. (Amaya); Quintero, P. (Pablo); Garcia-Gerique, L. (Laura); Gonzalez-Muniesa, P. (Pedro); Arraiza, S. (Suyen)
    Several studies have shown a pathological oxygenation (hypoxia/hyperoxia) on the adipose tissue in obese subjects. Additionally, the excess of body weight is often accompanied by a state of chronic low-degree inflammation.The inflammation phenomenon is a complex biological response mounted by tissues to combat injurious stimuli in order to maintain cell homeostasis. Furthermore, it is believed that the abnormal oxygen partial pressure occurring in adipose tissue is involved in triggering inflammatory processes. In this context, oxygen is used in modern medicine as a treatment for several diseases with inflammatory components. Thus, hyperbaric oxygenation has demonstrated beneficial effects, apart from improving local tissue oxygenation, on promoting angiogenesis, wound healing, providing neuroprotection, facilitating glucose uptake, appetite, and others. Nevertheless, an excessive hyperoxia exposure can lead to deleterious effects such as oxidative stress, pulmonary edema, and maybe inflammation. Interestingly, some of these favorable outcomes occur under high and low oxygen concentrations. Hereby, we review a potential therapeutic approach to the management of obesity as well as the oxygen-related inflammation accompanying expanded adipose tissue, based on elevated oxygen concentrations. To conclude, we highlight at the end of this review some areas that need further clarification.
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    Influence of different oxygen supply on metabolic markers and gene response in murine adipocytes
    (Wichtig Editore, 2012) Martinez, J.A. (José Alfredo); Quintero, P. (Pablo); Gonzalez-Muniesa, P. (Pedro)
    Obese subjects often present a low-grade chronic inflammation in the white adipose tissue, which seems to play an important role in the initiation and development of obesity-related diseases. It has been reported that this inflammatory process may be due to a hypoxic state occuring whithin this tissue. Oxygen is used in current medicine as a treatment for several conditions. The aim of this study was to analyze the effects of 95% O2 on specific metabolic variables and on the expression of some adipokines on murine adipocytes. 3T3-L1 adipocytes were exposed during 48 h to different treatments: 95% O2 hyperoxia (HPx group), CoCl2 (CoCl2 group), hyperoxia with CoCl2 (HPx+CoCl2 group) and 1%O2 hypoxia (Hx group). Cell viability, intracellular ROS content, glucose utilization, lactate and glycerol concentrations were measured. Also, mRNA expression of HIF-1[alfa], GLUT-1, ANGPTL4, PPAR-[gamma], adiponectin, IL-6 and MCP-1 genes was analyzed. Importantly, 95% O2 decreased cell viability and increased intracellular ROS production. Also, glycerol and lactate release were significantly increased and decreased, respectively, in HPx treated cells. This treatment also provoked a downregulation of GLUT-1 and ANGPTL-4, while IL-6 and MCP-1 were up-regulated. Exposure to a hyperoxia of 95% O2 seemed to provoke an inflammatory response in adipocytes. The two hypoxia-inducing conditions (CoCl2 and 1% O2) produced different outcomes in metabolic measurements as well as in the expression of some genes (GLUT-1, ANPGTL4, PPAR-[gamma] and adiponectin), while it remained similar in others (HIF-1[alfa], IL-6 and MCP-1). Indeed, hyperoxia increased significantly the ROS levels and the lipolytic activity, while it reduced lactate production. In addition to the effects on inflammation, the changes in GLUT-1, ANGPTL4 and PPAR-[gamma] genes let suppose that hyperoxia may be beneficial for the hypertrophied adipose tissues of obese subjects and for improving insulin sensitivity.