Examinando por Autor "Corrales, Patricia"

Mostrando 1 - 4 de 4

Chronic mercury at low doses impairs white adipose tissue plasticity
(Elsevier, 2019-02-23) Rizzetti, Danize Aparecida; Corrales, Patricia; Piagette, Janaina Trindade; Uranga, Jose Antonio; Vera, Gema; Peçanha, Franck Maciel; Vassallo, Dalton Valentim; Miguel, Marta; Wiggers, Giulia Alessandra
Introduction: The toxic effects of mercury (Hg) are involved in homeostasis of energy systems such as lipid and glucose metabolism, and white adipose tissue dysfunction is considered as a central mechanism leading to metabolic disorders. Objective: The aim of this study was to determine the effects of chronic inorganic Hg exposure at low doses on the lipid and glycemic metabolism. Methods: Male Wistar rats were divided into two groups and treated for 60 days with: saline solution, i.m. (Untreated) and mercury chloride, i.m. - 1st dose 4.6 μg/kg, subsequent doses 0.07 μg/kg/day - (Mercury). Histological analyses, Hg levels measurement and GRP78, CHOP, PPARα, PPARγ, leptin, adiponectin and CD11 mRNA expressions were performed in epididymal white adipose tissue (eWAT). Glucose, triglycerides, total cholesterol and insulin plasma levels were also measured. Results: Hg exposure reduced the absolute and relative eWAT weights, adipocyte size, plasma insulin levels, glucose tolerance, antioxidant defenses and increased plasma glucose and triglyceride levels. In addition, CHOP, GRP78, PPARα, PPARγ, leptin and adiponectin mRNA expressions were increased in Hg-treated animals. No differences in Hg concentration were found in eWAT between the untreated and Hg groups. These results suggest that the reduction in adipocyte size is related to the impaired antioxidant defenses, endoplasmic reticulum (ER) stress, the disrupted PPARs and adipokines mRNA expression induced by the metal in eWAT. These disturbances possibly induced a decrease in circulating insulin levels, an imbalance between lipolysis and lipogenesis mechanisms in eWAT, with an increase in fatty acids mobilization, a reduction in glucose uptake and an activation of pro-apoptotic pathways, leading to hyperglycemia and hyperlipidemia. Conclusions: Hg is a powerful environmental WAT disruptor that influences signaling events and impairs metabolic activity and hormonal balance of adipocytes.
Long-term caloric restriction ameliorates deleterious effects of aging on white and brown adipose tissue plasticity
(2019-06) Corrales, Patricia; Vivas, Yurena; Izquierdo-Lahuerta, Adriana; Hornillo, Daniel; Seoane-Collazo, Patricia; Velasco, Ismael; Torres, Lucia; López, Yamila; Martínez, Carmen; López, Miguel; Ros, Manuel; Obregon, María Jesús; Medina-Gomez, Gema
Age‐related increased adiposity is an important contributory factor in the development of insulin resistance (IR) and is associated with metabolic defects. Caloric restriction (CR) is known to induce weight loss and to decrease adiposity while preventing metabolic risk factors. Here, we show that moderate 20% CR delays early deleterious effects of aging on white and brown adipose tissue (WAT and BAT, respectively) function and improves peripheral IR. To elucidate the role of CR in delaying early signs of aging, young (3 months), middle‐aged (12 months), and old (20 months) mice fed al libitum and middle‐aged and old mice subjected to early‐onset CR were used. We show that impaired plasticity of subcutaneous WAT (scWAT) contributes to IR, which is already evident in middle‐aged mice. Moreover, alteration of thyroid axis status with age is an important factor contributing to BAT dysfunction in middle‐aged animals. Both defects in WAT and BAT/beige cells are ameliorated by CR. Accordingly, CR attenuated the age‐related decline in scWAT function and decreased the extent of fibro‐inflammation. Furthermore, CR promoted scWAT browning. In brief, our study identifies the contribution of scWAT impairment to age‐associated metabolic dysfunction and identifies browning in response to food restriction, as a potential therapeutic strategy to prevent the adverse metabolic effects in middle‐aged animals.
Transforming growth factor β3 deficiency promotes defective lipid metabolism and fibrosis in murine kidney
(COMPANY BIOLOGISTS, 2021-09-01) Escasany, Elia; Lanzón, Borja; Garcia-Carrasco, Almudena; Izquierdo-Lahuerta, Adriuana; Torres, Lucia; Corrales, Patricia; Rodríguez Rodríguez, Ana Elena; Luis-Lima, Sergio; Martínez-Álvarez, Concepción; Ruperez, Francisco Javier; Ros, Manuel; Porrini, Esteban; Rydén, Mikael; Medina-Gomez, Gema
Glomerulosclerosis and tubulointerstitial fibrosis are pathological features of chronic kidney disease. Transforming growth factor β (TGFβ) is a key player in the development of fibrosis. However, of the three known TGFβ isoforms, only TGFβ1 has an established role in fibrosis, and the pathophysiological relevance of TGFβ2 and TGFβ3 is unknown. Because Tgfb3 deficiency in mice results in early postnatal lethality, we analyzed the kidney phenotype of heterozygous Tgfb3-knockout mice (Tgfb3+/-) and compared it with that of matched wild-type mice. Four-month-old Tgfb3+/- mice exhibited incipient renal fibrosis with epithelial-mesenchymal transition, in addition to glomerular basement membrane thickening and podocyte foot process effacement associated with albuminuria. Also evident was insulin resistance and oxidative stress at the renal level, together with aberrant renal lipid metabolism and mitochondrial function. Omics analysis revealed toxic species, such as diacylglycerides and ceramides, and dysregulated mitochondrial metabolism in Tgfb3+/- mice. Kidneys of Tgfb3+/- mice showed morphological alterations of mitochondria and overactivation of non-canonical MAPK ERK1/2 and JNK cascades. Our study indicates that renal TGFβ3 might have antifibrotic and renoprotective properties, opposing or counteracting the activity of TGFβ1. This article has an associated First Person interview with the first author of the paper.
Transforming Growth Factor-β3 Regulates Adipocyte Number in Subcutaneous White Adipose Tissue
(CellPress, 2018-10-16) Petrus, Paul; Niklas, Mejhert; Corrales, Patricia; Lecoutre, Simon; Qian, Li; Maldonado, Estela; Kulyté, Agne; López, Yamila; Campbell, Mark; Acosta, Juan R; Laurencikiene, Jurga; Iyadh, Douagi; Gao, Hui; Martínez-Álvarez, Concepción; Hedén, Per; Spalding, Kirsty L; Vidal-Puig, Antonio; Medina-Gomez, Gema; Arner, Peter; Ryden, Mikael
White adipose tissue (WAT) mass is determined by adipocyte size and number. While adipocytes are continuously turned over, the mechanisms controlling fat cell number in WAT upon weight changes are unclear. Herein, prospective studies of human subcutaneous WAT demonstrate that weight gain increases both adipocyte size and number, but the latter remains unaltered after weight loss. Transcriptome analyses associate changes in adipocyte number with the expression of 79 genes. This gene set is enriched for growth factors, out of which one, transforming growth factor-β3 (TGFβ3), stimulates adipocyte progenitor proliferation, resulting in a higher number of cells undergoing differentiation in vitro. The relevance of these observations was corroborated in vivo where Tgfb3+/- mice, in comparison with wild-type littermates, display lower subcutaneous adipocyte progenitor proliferation, WAT hypertrophy, and glucose intolerance. TGFβ3 is therefore a regulator of subcutaneous adipocyte number and may link WAT morphology to glucose metabolism.