GUILHERME DA SILVA FERREIRA

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FFM, Hospital das Clínicas, Faculdade de Medicina
LIM/10 - Laboratório de Lípides, Hospital das Clínicas, Faculdade de Medicina

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  • article 3 Citação(ões) na Scopus
    Dietary sodium restriction alters muscle lipidomics that relates to insulin resistance in mice
    (2021) PINTO, Paula Ramos; YOSHINAGA, Marcos Y.; BIANCO, Vanessa Del; BOCHI, Ana Paula; FERREIRA, Guilherme S.; PINTO, Isabella F. D.; RODRIGUES, Leticia G.; NAKANDAKARE, Edna R.; OKAMOTO, Maristela M.; MACHADO, Ubiratan F.; MIYAMOTO, Sayuri; CATANOZI, Sergio; PASSARELLI, Marisa
    A low-sodium (LS) diet has been shown to reduce blood pressure (BP) and the incidence of cardiovascular diseases. However, severe dietary sodium restriction promotes insulin resistance (IR) and dyslipidemia in animal models and humans. Thus, further clarification of the long-term consequences of LS is needed. Here, we investigated the effects of chronic LS on gastrocnemius gene and protein expression and lipidomics and its association with IR and plasma lipids in LDL receptor knockout mice. Three-month-old male mice were fed a normal sodium diet (NS; 0.5% Na; n = 12-19) or LS (0.06% Na; n = 14-20) over 90 days. Body mass (BM), BP, plasma total cholesterol, triacylglycerol (TG), glucose, hematocrit, and IR were evaluated. LS increased BM (9%), plasma TG (51%), blood glucose (19%), and IR (46%) when compared with the NS. RT-qPCR analysis revealed that genes involved in lipid uptake and oxidation were increased by the LS: Fabp3 (106%), Prkaa1 (46%), and Cpt1 (74%). Genes and proteins (assessed by Western blotting) involved in insulin signaling were not changed by the LS. Similarly, lipid species classically involved in muscle IR, such as diacylglycerols and ceramides detected by ultra-high-performance liquid chromatography coupled to mass spectrometry, were also unchanged by LS. Species of phosphatidylcholines (68%), phosphatidylinositol (90%), and free fatty acids (59%) increased while cardiolipins (41%) and acylcarnitines (9%) decreased in gastrocnemius in response to LS and were associated with glucose disposal rate. Together these results suggest that chronic LS alters glycerophospholipid and fatty acids species in gastrocnemius that may contribute to glucose and lipid homeostasis derangements in mice.
  • article 7 Citação(ões) na Scopus
    Exercise Training Favorably Modulates Gene and Protein Expression That Regulate Arterial Cholesterol Content in CETP Transgenic Mice
    (2018) PINTO, Paula R.; SILVA, Karolline S. da; IBORRA, Rodrigo T.; OKUDA, Ligia S.; GOMES-KJERULF, Diego; FERREIRA, Guilherme S.; MACHADO-LIMA, Adriana; ROCCO, Debora D. F. M.; NAKANDAKARE, Edna R.; MACHADO, Ubiratan F.; CORREA-GIANNELLA, Maria L.; CATANOZI, Sergio; PASSARELLI, Marisa
    Aerobic exercise training (AET) improves the reverse cholesterol transport (RCT) in cholesteryl ester transfer protein-transgenic (CETP-tg) mice. We aimed at investigating the role of AET in the expression of genes and proteins involved in lipid flux in the aorta and macrophages of CETP-tg mice. Three-month-old male mice were randomly divided into trained (T; treadmill 15 m/min; 30 min/day) and sedentary (S) groups. After 6 weeks, peritoneal macrophages and the aortic arch were obtained immediately (0 h) or 48 h after the last exercise session. mRNA was determined by RT-qPCR, protein levels by immunoblot and C-14-cholesterol efflux determined in macrophages. AET did not change body weight, plasma cholesterol, triglycerides, glucose and CETP activity. In macrophages, at time 0 h, a higher expression of genes that encode PPAR gamma, ABCA-1 and a lower expression of MCP-1 and IL-10, was observed in T as compared to S. After 48 h, lower expressions of MCP-1 and PPAR gamma genes were observed in T mice. Increase in ABCA-1, SR-BI and IL-6 and decrease of LOX-1, MCP-1, TNF and IL-10 gene expression was observed in the aorta of T compared to S mice (0 h) and LOX-1 and MCP-1 remained diminished after 48 h. The protein level of MCP-1 and SR-BI in the aortic arch was unchanged in T animals after 48 h as compared to S, but LOX-1 was reduced confirming data of gene expression. The apo A-I and the HDL2 mediated-cholesterol efflux (8 and 24 h) were not different between T and S animals. In the presence of CETP, AET positively influences gene expression in the arterial wall and macrophages of CETP-tg mice contributing to the RCT and prevention of atherosclerosis. These changes were perceptible immediately after the exercise session and were influenced by the presence of CETP although independent of changes in its activity. Reductions in gene and protein expression of LOX-1 were parallel and reflect the ability of exercise training in reducing the uptake of modified LDL by the arterial wall macrophages.
  • conferenceObject
    LIPOPROTEINS AND LIPID METABOLISM: HDL. AEROBIC EXERCISE TRAINING DOES NOT SYSTEMATICALLY AFFECT MACROPHAGE GENE EXPRESSION INVOLVED IN REVERSE CHOLESTEROL TRANSPORT AND CHOLESTEROL EFFLUX IN CETP TRANSGENIC MICE
    (2016) PINTO, P. R.; SILVA, K. S.; GOMES, D. J.; MACHADO-LIMA, A.; IBORRA, R. T.; FERREIRA, G. S.; QUINTAO, E. C. R.; NAKANDAKARE, E. R.; MACHADO, U. F.; CORREA-GIANNELLA, M. L. C.; CATANOZI, S.; PASSARELLI, M.
  • conferenceObject
    PLASMA ADVANCED GLYCATION END PRODUCTS POSITIVELY CORRELATES TO OXYSTEROLS LEVELS IN CAROTID ATHEROSCLEROTIC PLAQUES
    (2020) PINTO, R. S.; FERREIRA, G. S.; SILVESTRE, G. C. R.; SANTANA, M. F. M.; LEDESMA, L.; PINTO, P. R.; MARCELINO, G. A.; SILVA, E. S. Da; PASSARELLI, M.
  • article 1 Citação(ões) na Scopus
    Monocyte-to-HDL ratio and non-HDL cholesterol were predictors of septic shock in newborns
    (2022) FONSECA, Fernanda Andrade Macaferri da da; ESPOSITO, Aline Paulino; SILVA, Maria Helena Baptista Nunes da; NUNES, Valeria Sutti; CAZITA, Patricia Miralda; FERREIRA, Guilherme Silva; CECCON, Maria Esther Jurfest Rivero; CARVALHO, Werther Brunow de; CARNEIRO-SAMPAIO, Magda; PALMEIRA, Patricia
    Background: The association between lipoprotein levels and late-onset neonatal sepsis has shown controversial results. The aims are to assess lipid profile, cytokines, and Monocyte-to-HDL (M/H) ratio as diagnostic and prog-nostic markers for late-onset neonatal sepsis.Methods: This prospective study included 49 septic neonates and 17 controls. Cholesterol (CT), Triglyceride (TG), Very-Low-Density (VLDLc), Low-Density (LDLc), and High-Density Lipoproteins (HDLc) were measured at admis-sion (D0) and on days 3, 7 and 10 to evaluate septic shock outcomes. Cytokines and monocytes were evaluated by flow cytometry.Results: Septic newborns showed higher IL-6 and IL-8 at D0 and CT levels on D7 and on D10, which also presented higher TG, VLDLc and non-HDL cholesterol concentrations than controls. The septic shock group (n = 22) revealed a higher number of male subjects, CRP, IL-6, IL-8 and IL-10 levels, while lower TG, HDLc, monocyte numbers and M/H ratio at admission compared to the non-shock group (n = 27). M/H ratio and non-HDL choles-terol on D0 were risk factors for septic shock (OR = 0.70, 0.49-0.99; OR = 0.96, 0.92-0.99, respectively). Decreasing levels from D0 to D3 of CT (OR = 0.96, 0.93-0.99), VLDLc (OR = 0.91, 0.85-0.98), and non-HDL cholesterol (OR = 0.92, 0.87-0.98) were also predictors of septic shock.Conclusions: Lower M/H ratios and non-HDL cholesterol at admission and decreasing levels of cholesterol, VLDLc and non-HDL cholesterol during a hospital stay are associated with the development of septic shock in newborns with late-onset neonatal sepsis.
  • article 0 Citação(ões) na Scopus
    The Prolonged Activation of the p65 Subunit of the NF-Kappa-B Nuclear Factor Sustains the Persistent Effect of Advanced Glycation End Products on Inflammatory Sensitization in Macrophages
    (2024) ASSIS, Sayonara Ivana Santos de; AMENDOLA, Leonardo Szalo; OKAMOTO, Maristela Mitiko; FERREIRA, Guilherme da Silva; IBORRA, Rodrigo Tallada; SANTOS, Danielle Ribeiro; SANTANA, Monique de Fatima Mello; SANTANA, Kelly Gomes; CORREA-GIANNELLA, Maria Lucia; BARBEIRO, Denise Frediani; SORIANO, Francisco Garcia; MACHADO, Ubiratan Fabres; PASSARELLI, Marisa
    Advanced glycation end products (AGEs) prime macrophages for lipopolysaccharide (LPS)-induced inflammation. We investigated the persistence of cellular AGE-sensitization to LPS, considering the nuclear content of p50 and p65 nuclear factor kappa B (NFKB) subunits and the expression of inflammatory genes. Macrophages treated with control (C) or AGE-albumin were rested for varying intervals in medium alone before being incubated with LPS. Comparisons were made using one-way ANOVA or Student t-test (n = 6). AGE-albumin primed macrophages for increased responsiveness to LPS, resulting in elevated levels of TNF, IL-6, and IL-1beta (1.5%, 9.4%, and 5.6%, respectively), compared to C-albumin. TNF, IL-6, and IL-1 beta secretion persisted for up to 24 h even after the removal of AGE-albumin (area under the curve greater by 1.6, 16, and 5.2 times, respectively). The expressions of Il6 and RelA were higher 8 h after albumin removal, and Il6 and Abca1 were higher 24 h after albumin removal. The nuclear content of p50 remained similar, but p65 showed a sustained increase (2.9 times) for up to 24 h in AGE-albumin-treated cells. The prolonged activation of the p65 subunit of NFKB contributes to the persistent effect of AGEs on macrophage inflammatory priming, which could be targeted for therapies to prevent complications based on the AGE-RAGE-NFKB axis.
  • article 7 Citação(ões) na Scopus
    Aerobic Exercise Training Prevents Insulin Resistance and Hepatic Lipid Accumulation in LDL Receptor Knockout Mice Chronically Fed a Low-Sodium Diet
    (2021) FERREIRA, Guilherme da Silva; BOCHI, Ana Paula Garcia; PINTO, Paula Ramos; BIANCO, Vanessa Del; RODRIGUES, Leticia Gomes; MORAIS, Mychel Raony Paiva Teixeira; NAKANDAKARE, Edna Regina; MACHADO, Ubiratan Fabres; CATANOZI, Sergio; PASSARELLI, Marisa
    Background: A low-sodium (LS) diet reduces blood pressure, contributing to the prevention of cardiovascular diseases. However, intense dietary sodium restriction impairs insulin sensitivity and worsens lipid profile. Considering the benefits of aerobic exercise training (AET), the effect of LS diet and AET in hepatic lipid content and gene expression was investigated in LDL receptor knockout (LDLr-KO) mice. Methods: Twelve-week-old male LDLr-KO mice fed a normal sodium (NS) or LS diet were kept sedentary (S) or trained (T) for 90 days. Body mass, plasma lipids, insulin tolerance testing, hepatic triglyceride (TG) content, gene expression, and citrate synthase (CS) activity were determined. Results were compared by 2-way ANOVA and Tukey's post-test. Results: Compared to NS, LS increased body mass and plasma TG, and impaired insulin sensitivity, which was prevented by AET. The LS-S group, but not the LS-T group, presented greater hepatic TG than the NS-S group. The LS diet increased the expression of genes related to insulin resistance (ApocIII, G6pc, Pck1) and reduced those involved in oxidative capacity (Prkaa1, Prkaa2, Ppara, Lipe) and lipoprotein assembly (Mttp). Conclusion: AET prevented the LS-diet-induced TG accumulation in the liver by improving insulin sensitivity and the expression of insulin-regulated genes and oxidative capacity.
  • article 20 Citação(ões) na Scopus
    Cholesterol metabolism in aging simultaneously altered in liver and nervous system
    (2022) NUNES, Valeria Sutti; FERREIRA, Guilherme da Silva; QUINTAO, Eder Carlos Rocha
    In humans, aging, triggers increased plasma concentrations of triglycerides, cholesterol, low-density lipoproteins and lower capacity of high-density lipoproteins to remove cellular cholesterol. Studies in rodents showed that aging led to cholesterol accumulation in the liver and decrease in the brain with reduced cholesterol synthesis and increased levels of cholesterol 24-hydroxylase, an enzyme responsible for removing cholesterol from the brain. Liver diseases are also related to brain aging, inducing changes in cholesterol metabolism in the brain and liver of rats. It has been suggested that late onset Alzheimer's disease is associated with metabolic syndrome. Non-alcoholic fatty liver is associated with lower total brain volume in the Framingham Heart Study offspring cohort study. Furthermore, disorders of cholesterol homeostasis in the adult brain are associated with neurological diseases such as Niemann-Pick, Alzheimer, Parkinson, Huntington and epilepsy. Apolipoprotein E (apoE) is important in transporting cholesterol from astrocytes to neurons in the etiology of sporadic Alzheimer's disease, an aging-related dementia. Desmosterol and 24S-hydroxycholesterol are reduced in ApoE KO hypercholesterolemic mice. ApoE KO mice have synaptic loss, cognitive dysfunction, and elevated plasma lipid levels that can affect brain function. In contrast to cholesterol itself, there is a continuous uptake of 27hydroxycholesterol in the brain as it crosses the blood-brain barrier and this flow can be an important link between intra-and extracerebral cholesterol homeostasis. Not surprisingly, changes in cholesterol metabolism occur simultaneously in the liver and nervous tissues and may be considered possible biomarkers of the liver and nervous system aging.
  • article 2 Citação(ões) na Scopus
    Aerobic Exercise Training Reduces Atherogenesis Induced by Low-Sodium Diet in LDL Receptor Knockout Mice
    (2022) BOCHI, Ana Paula Garcia; FERREIRA, Guilherme da Silva; BIANCO, Vanessa Del; PINTO, Paula Ramos; RODRIGUES, Leticia Gomes; TREVISANI, Mayara da Silva; FURUKAWA, Luzia Naoko Shinohara; BISPO, Kely Cristina Soares; SILVA, Alexandre Alves da; VELOSA, Ana Paula Pereira; NAKANDAKARE, Edna Regina; MACHADO, Ubiratan Fabres; TEODORO, Walcy Paganelli Rosolia; PASSARELLI, Marisa; CATANOZI, Sergio
    This study investigated the efficacy of aerobic exercise training (AET) in the prevention of dyslipidemia, insulin resistance (IR), and atherogenesis induced by severe low-sodium (LS) diet. LDL receptor knockout (LDLR KO) mice were fed a low-sodium (LS) (0.15% NaCl) or normal-sodium (NS; 1.27% NaCl) diet, submitted to AET in a treadmill, 5 times/week, 60 min/day, 15 m/min, for 90 days, or kept sedentary. Blood pressure (BP), plasma total cholesterol (TC) and triglyceride (TG) concentrations, lipoprotein profile, and insulin sensitivity were evaluated at the end of the AET protocol. Lipid infiltration, angiotensin II type 1 receptor (AT1), receptor for advanced glycation end products (RAGE), carboxymethyllysine (CML), and 4-hydroxynonenal (4-HNE) contents as well as gene expression were determined in the brachiocephalic trunk. BP and TC and gene expression were similar among groups. Compared to the NS diet, the LS diet increased vascular lipid infiltration, CML, RAGE, 4-HNE, plasma TG, LDL-cholesterol, and VLDL-TG. Conversely, the LS diet reduced vascular AT1 receptor, insulin sensitivity, HDL-cholesterol, and HDL-TG. AET prevented arterial lipid infiltration; increases in CML, RAGE, and 4-HNE contents; and reduced AT1 levels and improved LS-induced peripheral IR. The current study showed that AET counteracted the deleterious effects of chronic LS diet in an atherogenesis-prone model by ameliorating peripheral IR, lipid infiltration, CML, RAGE, 4-HNE, and AT1 receptor in the intima-media of the brachiocephalic trunk. These events occurred independently of the amelioration of plasma-lipid profile, which was negatively affected by the severe dietary-sodium restriction.
  • conferenceObject
    AEROBIC EXERCISE TRAINING REDUCES INSULIN RESISTANCE AND ATHEROGENESIS INDUCED BY LOW-SODIUM DIET IN LDL RECEPTOR KNOCKOUT MICE
    (2021) BOCHI, A. P. G.; FERREIRA, G. S.; PINTO, P. R.; BIANCO, V. Del; RODRIGUES, L. G.; TREVISANI, M. S.; BISPO, K. C. S.; CAPELOZZI, V. L.; NAKANDAKARE, E. R.; MACHADO, U. F.; TEODORO, W. R.; PASSARELLI, M.; CATANOZI, S.