Maternal obesity in mice exacerbates the allergic inflammatory response in the airways of male offspring

It was previously demonstrated that non-allergen-sensitized rodents born to mothers exposed to a high-fat diet (HFD) spontaneously develop lower respiratory compliance and higher respiratory resistance. In the present study, we sought to determine if mice born to mothers consuming HFD would exhibit changes in inflammatory response and lung remodeling when subjected to ovalbumin (OVA) sensitization/challenge in adult life. Mice born to dams consuming either HFD or standard chow had increased bronchoalveolar lavage (BAL) levels of IL-1 beta, IL-4, IL-5, IL-10, IL-13, TNF-alpha and TGF-beta 1 after challenge with OVA. IL-4, IL-13, TNF-alpha and TGF-beta 1 levels were further increased in the offspring of HFD-fed mothers. Mice born to obese dams also had exacerbated values of leukocyte infiltration in lung parenchyma, eosinophil and neutrophil counts in BAL, mucus overproduction and collagen deposition. The programming induced by maternal obesity was accompanied by increased expression of miR-155 in peripheral-blood mononuclear cells and reduced miR-133b in trachea and lung tissue in adult life. Altogether, the present data support the unprecedented notion that the progeny of obese mice display exacerbated responses to sensitization/challenge with OVA, leading to the intensification of the morphological changes of lung remodeling. Such changes are likely to result from long-lasting changes in miR-155 and miR-133b expression1112CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQCOORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL DE NÍVEL SUPERIOR - CAPESFUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESPsem informaçãosem informação2017/20742-2; 2016/22722-6; 2015/18997-7; 2013/07607-8; 2017/15175-

Prolonged fasting elicits increased hepatic triglyceride accumulation in rats born to dexamethasone-treated mothers

We investigated the effect of dexamethasone during the last week of pregnancy on glucose and lipid metabolism in male offspring. Twelve-week old offspring were evaluated after fasting for 12-hours (physiological) and 60-hours (prolonged). Physiological fasting resulted in glucose intolerance, decreased glucose clearance after pyruvate load and increased PEPCK expression in rats born to dexamethasone-treated mothers (DEX). Prolonged fasting resulted in increased glucose tolerance and increased glucose clearance after pyruvate load in DEX. These modulations were accompanied by accumulation of hepatic triglycerides (TG). Sixty-hour fasted DEX also showed increased citrate synthase (CS) activity, ATP citrate lyase (ACLY) content, and pyruvate kinase 2 (pkm2), glucose transporter 1 (slc2a1) and lactate dehydrogenase-a (ldha) expressions. Hepatic AKT2 was increased in 60-hour fasted DEX, in parallel with reduced miRNAs targeting the AKT2 gene. Altogether, we show that metabolic programming by prenatal dexamethasone is characterized by an unexpected hepatic TG accumulation during prolonged fasting. The underlying mechanism may depend on increased hepatic glycolytic flux due to increased pkm2 expression and consequent conversion of pyruvate to non-esterified fatty acid synthesis due to increased CS activity and ACLY levels. Upregulation of AKT2 due to reduced miRNAs may serve as a permanent mechanism leading to increased pkm2 expression.Sao Paulo Research Foundation (FAPESP)National Counsel of Technological and Scientific Development (CNPq)Coordination for the Improvement of Higher Level or Education Personnel (CAPES)Univ Sao Paulo, Inst Biomed Sci, Dept Physiol & Biophys, Sao Paulo, BrazilUniv Estadual Campinas, Fac Med Sci, Dept Pharmacol, Campinas, SP, BrazilUniv Fed Sao Paulo, Inst Environm Chem & Pharmaceut Sci, Diadema, BrazilUniv Fed Sao Paulo, Inst Environm Chem & Pharmaceut Sci, Diadema, BrazilWeb of Scienc

Dehydroepiandrosterone on metabolism and the cardiovascular system in the postmenopausal period

Dehydroepiandrosterone (DHEA), mostly present as its sulfated ester (DHEA-S), is an anabolic hormone that naturally declines with age. Furthermore, it is the most abundant androgen and estrogen precursor in humans. Low plasma levels of DHEA have been strongly associated with obesity, insulin resistance, dyslipidemia, and high blood pressure, increasing the risk of cardiovascular disease. In this respect, DHEA could be regarded as a promising agent against metabolic syndrome (MetS) in postmenopausal women, since several age-related metabolic diseases are reported during aging. There are plenty of experimental evidences showing beneficial effects after DHEA therapy on carbohydrate and lipid metabolism, as well as cardiovascular health. However, its potential as a therapeutic agent appears to attract controversy, due to the lack of effects on some symptoms related to MetS. In this review, we examine the available literature regarding the impact of DHEA therapy on adiposity, glucose metabolism, and the cardiovascular system in the postmenopausal period. Both clinical studies and in vitro and in vivo experimental models were selected, and where possible, the main cellular mechanisms involved in DHEA therapy were discussed983957CAPES - Coordenação de Aperfeiçoamento de Pessoal e Nível SuperiorCNPQ - Conselho Nacional de Desenvolvimento Científico e TecnológicoFAPESP – Fundação de Amparo à Pesquisa Do Estado De São Paulo0012012/14183-7303543/2014-

Topical insulin modulates inflammatory and proliferative phases of burn-wound healing in diabetes-induced rats

The healing time of burn wounds depends on surface area and depth of the burn and associated comorbidities. Diabetes mellitus (DM) causes delays in the healing process by extending the inflammatory phase. Treatment with topical insulin can improve the inflammatory phase, restore metabolic dysregulation, and modulate impaired cellular signaling in burn wounds. The objective of this study was to evaluate markers of the inflammatory and proliferative phases of second-degree burns after topical insulin treatment in diabetic rats. Type I DM was induced with streptozotocin in male Wistar rats. The animals' backs were shaved and subjected to thermal burning. Rats were randomized into two groups: control diabetic (DC) and insulin diabetic (DI). At Days 7 and 14 postburn, rats were euthanized, and wound-tissue sections were evaluated by hematoxylin and eosin, Weigert, and Verhoeff staining, immunohistochemistry-paraffin, and enzyme-linked immunosorbent assay. A significant increase in reepithelialization was seen on Days 7 and 14 in DI versus DC rats. On Day 7, interleukin (IL)-1 beta, IL-6, monocyte chemotactic protein (MCP)-1, and F4/80 expression were increased in DI versus DC rats. On Day 14, MCP-1 expression was decreased and F4/80 increased in DI versus DC rats. On Days 7 and 14, Ki-67, transforming growth factor-beta 1, vascular endothelial growth factor expression, and formation of elastic fibers were increased in DI versus DC rats. Topical insulin modulates burn-wound healing in diabetic animals by balancing inflammation and promoting angiogenesis and formation of elastic fibers215473484sem informaçãosem informaçã