Garcia-Diaz, D.F. (Diego F.)
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- Fat intake leads to differential response of rat adipocytes to glucose, insulin and ascorbic acid(Royal Society of Medicine Press, 2012) Martinez, J.A. (José Alfredo); Garcia-Diaz, D.F. (Diego F.); Moreno-Aliaga, M. J. (María Jesús); Milagro-Yoldi, F.I. (Fermín Ignacio); Arellano, A.V. (A.V.); Campión-Zabalza, J. (Javier)Antioxidant-based treatments have emerged as novel and interesting approaches to counteract fat accumulation in obesity and associated metabolic disturbances. Adipocytes from rats that were fed on chow or high-fat diet (HFD) for 50 d were isolated (primary adipocytes) and incubated (72 h) on low (LG; 5.6 mmol/L) or high (HG; 25 mmol/L) glucose levels, in the presence or absence of 1.6 nmol/L insulin and 200 μmol/L vitamin C (VC). Adipocytes from HFD-fed animals presented lower insulin-induced glucose uptake, lower lactate and glycerol release, and lower insulin-induced secretion of some adipokines as compared with controls. HG treatment restored the blunted response to insulin regarding apelin secretion in adipocytes from HFD-fed rats. VC treatment inhibited the levels of nearly all variables, irrespective of the adipocytes' dietary origin. The HG treatment reduced adipocyte viability, and VC protected from this toxic effect, although more drastically in control adipocytes. Summing up, in vivo chow or HFD intake determines a differential response to insulin and glucose treatments that appears to be dependent on the insulin-resistance status of the adipocytes, while VC modifies some responses from adipocytes independently of the previous dietary intake of the animals.
- Obesity induced by a pair-fed high fat sucrose diet: methylation and expression pattern of genes related to energy homeostasis.(BioMed Central, 2010) Martinez, J.A. (José Alfredo); Garcia-Diaz, D.F. (Diego F.); Lomba-Piquer, A. (Almudena); Milagro-Yoldi, F.I. (Fermín Ignacio); Campión-Zabalza, J. (Javier); Marti-del-Moral, A. (Amelia)BACKGROUND: The expression of some genes controlling energy homeostasis could be regulated by epigenetic mechanisms that may play a role in body weight regulation. Thus, it is known that various nutritional factors affect DNA methylation. In order to assess whether the macronutrient composition of the diet could be related to the epigenetic regulation of gene expression and with obesity development, we investigated the effects on methylation and expression patterns of two pair-fed isocaloric diets in rats: control (rich in starch) and HFS (rich in fat and sucrose). RESULTS: The pair-fed HFS diet induced higher weight gain and adiposity as compared to the controls as well as liver triglyceride accumulation and oxidative stress. Feeding the HFS diet impaired glucose tolerance and serum triglycerides and cholesterol. Liver glucokinase expression, a key glycolytic gene, remained unaltered, as well as the mRNA values of fatty acid synthase and NADH dehydrogenase (ubiquinone) 1 beta subcomplex, 6 (NDUFB6) in liver and visceral adipocytes, which regulate lipogenesis and mitochondrial oxidative metabolism, respectively. Liver expression of hydroxyacyl-coenzyme A dehydrogenase (HADHB), a key gene of beta-oxidation pathway, was higher in the HFS-fed animals. However, the methylation status of CpG islands in HADHB and glucokinase genes remained unchanged after feeding the HFS diet. CONCLUSIONS: These results confirm that the distribution and type of macronutrients (starch vs. sucrose, and percent of fat) influence obesity onset and the associated metabolic complications. HFS diets produce obesity independently of total energy intake, although apparently no epigenetic (DNA methylation) changes accompanied the modifications observed in gene expression.
- Glucose and insulin modify thrombospondin 1 expression and secretion in primary adipocytes from diet-induced obese rats.(Springer, 2011) Martinez, J.A. (José Alfredo); Garcia-Diaz, D.F. (Diego F.); Moreno-Aliaga, M. J. (María Jesús); Milagro-Yoldi, F.I. (Fermín Ignacio); Arellano, A.V. (A.V.); Portillo, M.P. (María P.); Campión-Zabalza, J. (Javier)Thrombospondin 1 (TSP-1), an anti-angiogenic factor and TGF-β activity regulator, has been recently recognized as an adipokine that correlates with obesity, inflammation and insulin-resistance processes. In the present study, epididymal adipocytes of rats that were fed a chow (C) or a high fat diet (HFD) for 50 days, were isolated and incubated (24-72 h) in low (LG; 5.6 mM) or high (HG; 25 mM) glucose, in presence or absence of 1.6 nM insulin. Rats fed the HF diet showed an established obesity state. Serum TSP-1 levels and TSP-1 mRNA basal expression of adipocytes from HFD rats were higher than those from controls. Adipocytes from HFD animals presented an insulin-resistance state, as suggested by the lower insulin-stimulated glucose uptake as compared to controls. TSP-1 expression in culture was higher in adipocytes from obese animals at 24 h, but when the adipocytes were treated with HG, these expression levels dropped dramatically. Later at 72 h, TSP-1 expression was lower in adipocytes from HFD rats, and no effects of the other treatments were observed. Surprisingly, the secretion levels of this protein at 72 h were increased significantly by the HG treatment in both types of adipocytes, although they were even higher in adipocytes from obese animals. Finally, cell viability was significantly reduced by HG treatment in both types of adipocytes. In summary, TSP-1 expression/secretion was modulated in an in vitro model of insulin-resistant adipocytes. The difference between expression and secretion patterns suggests a post-transcriptional regulation. The present study confirms that TPS-1 is closely associated with obesity-related mechanisms.
- 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.
- 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.
- Molecular basis of the inflammation related to obesity(Hindawi Limited, 2019) Garcia-Diaz, D.F. (Diego F.); Gonzalez-Muniesa, P. (Pedro); Crujeiras, A.B. (Ana B.); Stachowska, E. (Ewa); Cordero, P. (Paul)Almost two thousand millions of adults suffer from overweight or obesity in the world [1]. After decades of research, we understand that the solution to this problem is not easy, as the pernicious trend is still increasing. This disease is defined as an excessive fat accumulation together with a moderate but chronic inflammation. This accompanying proinflammatory status is considered the link between obesity and the development of its related comorbidities such as insulin resistance and type 2 diabetes, cardiovascular diseases, cancer, and nonalcoholic fatty liver disease .