GUILHERME DA SILVA FERREIRA
Projetos de Pesquisa
Unidades Organizacionais
FFM, Hospital das Clínicas, Faculdade de Medicina
LIM/10 - Laboratório de Lípides, Hospital das Clínicas, Faculdade de Medicina
LIM/10 - Laboratório de Lípides, Hospital das Clínicas, Faculdade de Medicina
10 resultados
Resultados de Busca
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- 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, MarisaA 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.
- 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, MarisaAerobic 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.- 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, MarisaBackground: 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.
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.- Aerobic exercise training enhances the in vivo cholesterol trafficking from macrophages to the liver independently of changes in the expression of genes involved in lipid flux in macrophages and aorta(2015) PINTO, Paula Ramos; ROCCO, Debora Dias Ferraretto Moura; OKUDA, Ligia Shimabukuro; MACHADO-LIMA, Adriana; CASTILHO, Gabriela; SILVA, Karolline Santana da; GOMES, Diego Juvenal; PINTO, Raphael de Souza; IBORRA, Rodrigo Tallada; FERREIRA, Guilherme da Silva; NAKANDAKARE, Edna Regina; MACHADO, Ubiratan Fabres; CORREA-GIANNELLA, Maria Lucia Cardillo; CATANOZI, Sergio; PASSARELLI, MarisaBackground: Regular exercise prevents and regresses atherosclerosis by improving lipid metabolism and antioxidant defenses. Exercise ameliorates the reverse cholesterol transport (RCT), an antiatherogenic system that drives cholesterol from arterial macrophages to the liver for excretion into bile and feces. In this study we analyzed the role of aerobic exercise on the in vivo RCT and expression of genes and proteins involved in lipid flux and inflammation in peritoneal macrophages, aortic arch and liver from wild type mice. Methods: Twelve-week-old male mice were divided into sedentary and trained groups. Exercise training was performed in a treadmill (15 m/min, 30 min/day, 5 days/week). Plasma lipids were determined by enzymatic methods and lipoprotein profile by fast protein liquid chromatography. After intraperitoneal injection of J774-macrophages the RCT was assessed by measuring the recovery of H-3-cholesterol in plasma, feces and liver. The expression of liver receptors was determined by immunoblot, macrophages and aortic mRNAs by qRT-PCR. C-14-cholesterol efflux mediated by apo A-I and HDL2 and the uptake of H-3-cholesteryl oleoyl ether (H-3-COE)-acetylated-LDL were determined in macrophages isolated from sedentary and trained animals 48 h after the last exercise session. Results: Body weight, plasma lipids, lipoprotein profile, glucose and blood pressure were not modified by exercise training. A greater amount of H-3-cholesterol was recovered in plasma (24 h and 48 h) and liver (48 h) from trained animals in comparison to sedentary. No difference was found in H-3-cholesterol excreted in feces between trained and sedentary mice. The hepatic expression of scavenger receptor class B type I (SR-BI) and LDL receptor (B-E) was enhanced by exercise. We observed 2.8 and 1.7 fold rise, respectively, in LXR and Cyp7a mRNA in the liver of trained as compared to sedentary mice. Macrophage and aortic expression of genes involved in lipid efflux was not systematically changed by physical exercise. In agreement, C-14-cholestrol efflux and uptake of H-3-COE-acetylated-LDL by macrophages was similar between sedentary and trained animals. Conclusion: Aerobic exercise in vivo accelerates the traffic of cholesterol from macrophages to the liver contributing to prevention and regression of atherosclerosis, independently of changes in macrophage and aorta gene expression.
- Plasma advanced glycation end products and soluble receptor for advanced glycation end products as indicators of sterol content in human carotid atherosclerotic plaques(2022) PINTO, Raphael S.; FERREIRA, Guilherme S.; SILVESTRE, Gina Camillo R.; SANTANA, Monique de Fatima M.; NUNES, Valeria S.; LEDESMA, Lucas; PINTO, Paula R.; ASSIS, Sayonara Ivana S. de; MACHADO, Ubiratan F.; SILVA, Erasmo S. da; PASSARELLI, MarisaAdvanced glycation end products (AGEs) are independently related to cardiovascular disease (CVD) and favor cholesterol and oxysterol accumulation in macrophage foam cells. Soluble RAGE (sRAGE) impairs cellular AGE signaling alleviating the deleterious effects of AGE in atherogenesis. The association between plasma AGEs and sRAGE with the content of cholesterol, markers of cholesterol synthesis and absorption, and oxysterols in atherosclerotic plaques was evaluated in subjects undergoing carotid endarterectomy. Plasma and carotid plaques were obtained from symptomatic (n = 23) and asymptomatic subjects (n = 40). Lipids from plaques were extracted and sterols (oxysterols, cholesterol, desmosterol, lathosterol, sitosterol, and campesterol) were determined by using gas chromatography/mass spectrometry. Plasma total AGEs and pentosidine were measured by using fluorimetry and sRAGE by using ELISA. In symptomatic subjects ' atherosclerotic plaques, an increased amount of cholesterol (3x) and oxysterols [7 alpha-hydroxycholesterol (1.4x); 7 beta-hydroxycholesterol (1.2x); 25-hydroxycholesterol (1.3x); 24-hydroxycholesterol (2.7x), and 27-hydroxycholesterol, (1.15x)], with exception to 7 ketocholesterol, were found in comparison to asymptomatic individuals. Plasma total AGEs and pentosidine significantly and positively correlated to sterols accumulated in the atherosclerotic lesion, including cholesterol, desmosterol, campesterol, sitosterol, and oxysterols. On the other hand, sRAGE inversely correlated to total AGEs and pentosidine in plasma, and with major species of oxysterols, cholesterol, and markers of cholesterol synthesis and absorption in the atherosclerotic lesion. In multiple regression analyses, it was observed a significant inverse correlation between sRAGE and 24-hydroxycholesterol and desmosterol, and a positive significant correlation between pentosidine and 24-hydroxycholesterol, 27-hydroxycholesterol, and campesterol. In conclusion, the plasma concentration of AGEs and sRAGE is a tool to predict the accumulation of sterols in atherosclerotic lesions in symptomatic and asymptomatic individuals, helping to prevent and improve the management of acute cardiovascular complications.
conferenceObject LOW-SODIUM DIET INCREASES INSULIN RESISTANCE AND FAVORS FAT ACCUMULATION IN THE LIVER OF LDL RECEPTOR KNOCKOUT MICE(2020) FERREIRA, G. S.; PINTO, P. R.; BIANCO, V. D.; BOCHI, A. P. G.; TREVISANI, M. D. S.; RODRIGUES, L. G.; MORAES, M. R. P. T.; NAKANDAKARE, E. R.; MACHADO, U. F.; CATANOZI, S.; PASSARELLI, M.- Aerobic Exercise Training Selectively Changes Oxysterol Levels and Metabolism Reducing Cholesterol Accumulation in the Aorta of Dyslipidemic Mice(2017) FERREIRA, Guilherme Silva; PINTO, Paula R.; IBORRA, Rodrigo T.; BIANCO, Vanessa Del; SANTANA, Monique Fatima Mello; NAKANDAKARE, Edna Regina; NUNES, Valeria S.; NEGRAO, Carlos E.; CATANOZI, Sergio; PASSARELLI, MarisaBackground: Oxysterols are bioactive lipids that control cellular cholesterol synthesis, uptake, and exportation besides mediating inflammation and cytotoxicity that modulate the development of atherosclerosis. Aerobic exercise training (AET) prevents and regresses atherosclerosis by the improvement of lipid metabolism, reverse cholesterol transport (RCT) and antioxidant defenses in the arterial wall. We investigated in dyslipidemic mice the role of a 6-week AET program in the content of plasma and aortic arch cholesterol and oxysterols, the expression of genes related to cholesterol flux and the effect of the exercise-mimetic AICAR, an AMPK activator, in macrophage oxysterols concentration. Methods: Sixteen-week old male apo E KO mice fed a chow diet were included in the protocol. Animals were trained in a treadmill running, 15 m/min, 5 days/week, for 60 min (T; n = 29). A control group was kept sedentary (S; n = 32). Plasma lipids and glucose were determined by enzymatic techniques and glucometer, respectively. Cholesterol and oxysterols in aortic arch and macrophages were measured by gas chromatography/mass spectrometry. The expression of genes involved in lipid metabolism was determined by RT-qPCR. The effect of AMPK in oxysterols metabolism was determined in J774 macrophages treated with 0.25 mM AICAR. Results: Body weight and plasma TC, TG, HDL-c, glucose, and oxysterols were similar between groups. As compared to S group, AET enhanced 7 beta-hydroxycholesterol (70%) and reduced cholesterol (32%) in aorta. In addition, exercise increased Cyp27a1 (54%), Cd36 (75%), Cat (70%), Prkaa1 (40%), and Prkaa2 (51%) mRNA. In macrophages, the activation of AMPK followed by incubation with HDL2 increased Abca1 (52%) and Cd36 (220%) and decrease Prkaa1 (19%), Cyp27a1 (47%) and 7a-hydroxycholesterol level. Conclusion: AET increases 7 beta-hydroxycholesterol in the aortic arch of dyslipidemic mice, which is related to the enhanced expression of Cd36. In addition, the increase and reduction of Cyp27a1 and Cyp7b1 in trained mice may contribute to enhance levels of 27-OH C. Both oxysterols may act as an alternative pathway for the RCT contributing to the reduction of cholesterol in the aortic arch preventing atherogenesis.