LUZIA NAOKO SHINOHARA FURUKAWA
Projetos de Pesquisa
Unidades Organizacionais
Departamento de Clínica Médica, Faculdade de Medicina
LIM/16 - Laboratório de Fisiopatologia Renal, Hospital das Clínicas, Faculdade de Medicina
LIM/16 - Laboratório de Fisiopatologia Renal, Hospital das Clínicas, Faculdade de Medicina
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- Igf1 DNA methylation, epigenetics, and low-salt diet in fetal programming(2019) SIQUEIRA, F. R. De; FURUKAWA, L. N. S.; HEIMANN, J. C.All cells of an organism share the same DNA sequence from the time they are stem cells up to the time they are fully differentiated, distinct greatly in relation to the profile of expressed genes. Changes in gene expression which do not involve changes in DNA sequence of the nucleotides are currently known as an epigenetic phenomenon. Epigenetic changes play a fundamental role in the human gene expression and in the mechanism of association between events that occur early in life and alterations in adult life. Thus, in response to an adverse environment in which pregnant women are exposed during the perinatal or neonatal period, epigenetic modifications may lead to alterations in growth and metabolism in later life. Modification of histones (proteins found in eukaryotic cell nucleus) and DNA methylation (a process by which methyl groups are added to DNA) are the major epigenetic mechanisms involved in the regulation of gene expression. Maternal insults, mainly inadequate nutrition that may occur during sensitive or critical periods of fetal development (periods of rapid cell division), can program changes in the structure and functionality of cells, tissues, and/or organ systems. These changes may result in premature consequences in the offspring such as low birth weight and/or chronic diseases (hypertension, insulin resistance, obesity, etc.) in adulthood. A low-salt diet during pregnancy has been associated with low birth weight and chronic diseases in adult offspring, at least in the experimental setting. The expression of genes as insulin-like growth factors is regulated in a tissue-specific manner and can be altered by nutritional and endocrine conditions in utero. It is known that the major mediator of fetal growth is insulin-like growth factor type 1 (IGF-1) and insulin. The low birth weight may be due to low serum IGF-1 and/or by Igf1 epigenetic changes in fetus in response to low-salt intake during pregnancy. This observation might underlie the altered offspring phenotypes in this model since growth and insulin sensitivity are modulated by hepatic IGF-1. A low birth weight is related to low Igf1 gene expression and high Igf1 DNA methylation levels induced by low-salt intake during pregnancy. The variation in the IGF-1 serum levels may be due to changes in Igf1 gene promoter methylation. This concept is supported by increased methylation that is often associated with reduced gene expression. The methylation of genes changed as the offspring aged, indicating that epigenetic changes can occur and can be reversed during postnatal life. Further studies are needed to confirm or not if the observed results are reproducible in humans in order to recommend low dietary salt consumption during pregnancy. © Springer Nature Switzerland AG 2019. All rights reserved.
- High maternal sodium intake alters sex-specific renal renin-angiotensin system components in newborn Wistar offspring(2016) MAIA, D. R. R.; LOPES, K. L.; HEIMANN, J. C.; FURUKAWA, L. N. S.This study aimed to evaluate the systemic and renal renin-angiotensin-aldosterone system (RAAS) at birth in male and female offspring and in mothers fed a high sodium diet (HSD) before and during gestation. Female Wistar rats were fed a HSD (8.0% NaCl) or a normal sodium diet (1.3% NaCl) from 8 weeks of age until delivery of their first litter. Maternal body weight, tail blood pressure, and food and water intake were evaluated. The litter sizes were assessed, and the body and kidney weights of the offspring were measured. Both mothers and offspring were euthanized immediately following the birth of the pups to evaluate plasma renin activity (PRA), renal renin content (RRC), renal angiotensin-converting enzyme (ACE) activity, renal angiotensin (Ang) II content, serum aldosterone (ALDO) levels, and renal cortical and medullary renin messenger RNA expression. In mothers in the HSD group, water intake and kidney mass were higher, whereas renal ACE activity, Ang II, PRA, ALDO and RRC were decreased. In the offspring of HSD-fed dams, the body and kidney mass were lower in both genders, renal ACE activity was lower in females and renal Ang II was lower in males. PRA, RRC, renin gene expression and ALDO levels did not differ between the groups of offspring. The data presented herein showed that a maternal HSD during pregnancy induces low birth weight and a sex-specific response in the RAAS in offspring.
- Maternal high-sodium intake alters the responsiveness of the renin-angiotensin system in adult offspring(2012) RAMOS, Debora R.; COSTA, Nauilo L.; JANG, Karen L. L.; OLIVEIRA, Ivone B.; SILVA, Alexandre A. da; HEIMANN, Joel C.; FURUKAWA, Luzia N. S.Aims: The goal of the current study was to evaluate the impact of maternal sodium intake during gestation on the systemic and renal renin-angiotensin-aldosterone-system (RAAS) of the adult offspring. Main methods: Female Wistar rats were fed high- (HSD-8.0% NaCl) or normal-sodium diets (NSD-1.3% NaCl) from 8 weeks of age until the delivery of their first litter. After birth, the offspring received NSD. Tail-cuff blood pressure (TcBP) was measured in the offspring between 6 and 12 weeks of age. At 12 weeks of age, the offspring were subjected to either one week of HSD or low sodium diet (LSD-0.1 6%NaCl) feeding to evaluate RAAS responsiveness or to acute saline overload to examine sodium excretory function. Plasma (PRA) and renal renin content (RRC), serum aldosterone (ALDO) levels, and renal cortical and medullary renin mRNA expression levels were evaluated at the end of the study. Key findings: TcBP was higher among dams fed HSD, but no TcBP differences were observed among the offspring. Male offspring, however, exhibited increased TcBP after one week of HSD feeding, and this effect was independent of maternal diet. Increased RAAS responsiveness to the HSD and LSD was also observed in male offspring. The baseline levels of PRA. ALDO, and cortical and medullary renin gene expression were lower but the RRC levels were higher among HSD-fed male offspring (HSDoff). Conversely, female HSDoff showed reduced sodium excretion 4 h after saline overload compared with female NSDoff. Significance: High maternal sodium intake is associated with gender-specific changes in RAAS responsiveness among adult offspring.
conferenceObject Effect of an angiotensin II type 2 receptor agonist on myocardial hypertrophy and fibrosis induced by high salt diet(2017) DOPONA, Ellen Priscila Brito; ROCHA, Veronica Favoni; OLIVEIRA, Ivone Braga de; FURUKAWA, Luzia Naoko Shinohara; HEIMANN, Joel ClaudioconferenceObject Small litter size at birth is associated with insulin resistance and low energy expenditure in adulthood(2013) TAVARES, Neuziane Kloos Amorim; AGUIAR, Fernanda de Jesus; FURUKAWA, Luzia Naoko; HEIMANN, Joel ClaudioObjective: To evaluate the effect of litter size standardization at birth on adult metabolic parameters.Methods: Female Wistar rats became pregnant at 12 weeks of age. Offspring were divided into control(C), G8(8) and G4(4 newborns/litter) groups. At 12 weeks of age, food intake (FI,g/day), glucose (G,mg/dL), insulin (I,pM), cholesterol (Chol,mg/dL), triacylglycerols (TAG,mg/dL) levels, white and brown adipose tissue (BAT) masses (g/100g) adiposity index (AI,% body weight) were determined. Conclusion: Results suggest that changes in litter size is associated with energy balance, carbohydrate and lipid disorders, insulin resistance and alterations in blood pressure in adult male and female.conferenceObject Small litter size at birth is associated with insulin resistance and low energy expenditure in adulthood(2013) TAVARES, N. K. A.; AGUIAR, F. J.; FURUKAWA, L. N. S.; HEIMANN, J. C.Objective: To evaluate the effect of litter size standardization at birth on adult metabolic parameters. Methods: Female Wistar rats were mated and became pregnant at 12 weeks of age. Offspring were divided into control(C), S8(8) and S4(4 newborns/litter) groups. At 12 weeks of age, food intake (FI,g/day), glucose (G,mg/dL), insulin (I,pM), cholesterol (Chol,mg/dL), triacylglycerols (TAG,mg/dL) levels, white and brown adipose tissue (BAT) masses (g/100g) adiposity index (AI,% BW) were determined. Results: (mean±SEM p<0.05, n=6to32)1p<0.05 vs C and S8; 2p<0.05 vs S8 and S4; 3p<0.05 vs C; 4p<0.05 vs S8 Conclusion: Results suggest that the litter size is associated with insulin resistance and low energy expenditure in adulthood.conferenceObject Chronic Kidney Disease-Associated Frailty is characterized by changes in Muscular Expression of RANKL and FNDC5, which are partially reverted after Parathyroidectomy(2023) DUQUE, Eduardo J.; CRISPILHO, Shirley; OLIVEIRA, Ivone B.; REIS, Luciene M. dos; FURUKAWA, Luzia; TAKAYAMA, Liliam; PEREIRA, Rosa M.; SHINJO, Samuel K.; AVESANI, Carla; JORGETTI, Vanda; ELIAS, Rosilene M.; MOYSES, Rosa M.- Salt intake during pregnancy alters offspring's myocardial structure(2013) ALVES-RODRIGUES, E. N.; VERAS, M. M.; ROSA, K. T.; CASTRO, I. de; FURUKAWA, L. N. S.; OLIVEIRA, I. B.; SOUZA, R. M.; HEIMANN, J. C.Background and Aim: To evaluate the effects of low or high salt intake during pregnancy on left ventricle of adult male offspring. Methods and results: Low-(LS, 0.15%), normal-(NS, 1.3%) or high-salt (HS, 8% NaCl) diet was given to Wistar rats during pregnancy. During lactation all dams received NS as well as the offspring after weaning. To evaluate cardiac response to salt overload, 50% of each offspring group was fed a high-salt (hs, 4% NaCl) diet from the 21st to the 36th week of age (LShs, NShs, HShs). The remaining 50% was maintained on NS (LSns, NSns and HSns). Echocardiography was done at 20 and 30 weeks of age. Mean blood pressure (MBP), histology and left ventricular angiotensin II content (AII) were analyzed at 36 weeks of age. Interventricular septum, left ventricular posterior wall and relative wall thickness increased from the 20th to the 30th week of age only in HShs, cardiomyocyte mean volume was higher in HShs compared to NShs, LShs and HSns. AII and left ventricular fibrosis were not different among groups. Conclusions: HS during pregnancy programs adult male offspring to a blood pressure and angiotensin II independent concentric left ventricular hypertrophy, with no fibrosis, in response to a chronic high-salt intake.
bookPart 0 Citação(ões) na Scopus Impact of low-salt diet(2019) SIQUEIRA, F. R. De; OLIVEIRA, K. C. De; HEIMANN, J. C.; FURUKAWA, L. N. S.Studies in experimental animals and in groups of humans and epidemiological studies have shown that the sodium chloride or salt (sodium, Na, NaCl) plays an important role mainly in the regulation of blood pressure and represents an important environmental factor involved in the genesis of cardiovascular diseases. Therefore, salt intake in the population has been a constant concern. Variable blood pressure responses to different content in sodium intake are found in experimental hypertension models and in humans, and the reasons for such heterogeneity are not fully elucidated. The reduction of dietary sodium intake is recommended by public health as one of the non-medicated treatments for hypertension and consequently reducing the risk of cardiovascular diseases. However, some studies have demonstrated side effects of salt dietary restriction, reporting changes in glucose metabolism (hyperinsulinemia and insulin resistance), and these alterations are gender and time specific in experimental and population studies. © Springer Nature Switzerland AG 2019.conferenceObject Salt intake during pregnancy influences offspring organ growth(2014) PERES, Maria; OLIVEIRA, Ivone de; FURUKAWA, Luzia; GUIMARAES, Carina; HEIMANN, Joel