VALERIA SUTTI NUNES
Projetos de Pesquisa
Unidades Organizacionais
LIM/10 - Laboratório de Lípides, Hospital das Clínicas, Faculdade de Medicina
14 resultados
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- Dietary interesterified fat enriched with palmitic acid induces atherosclerosis by impairing macrophage cholesterol efflux and eliciting inflammation(2016) AFONSO, Milessa Silva; LAVRADOR, Maria Silvia Ferrari; KOIKE, Marcia Kiyomi; CINTRA, Dennys Esper; FERREIRA, Fabiana Dias; NUNES, Valeria Sutti; CASTILHO, Gabriela; GIOIELLI, Luiz Antonio; BOMBO, Renata Paula; CATANOZI, Sergio; CALDINI, Elia Garcia; DAMACENO-RODRIGUES, Nilsa Regina; PASSARELLI, Marisa; NAKANDAKARE, Edna Regina; LOTTENBERG, Ana MariaInteresterified fats are currently being used to replace trans fatty acids. However, their impact on biological pathways involved in the atherosclerosis development was not investigated. Weaning male LDLr-KO mice were fed for 16 weeks on a high-fat diet (40% energy as fat) containing polyunsaturated (PUFA), TRANS, palmitic (PALM), palmitic interesterified (PALM INTER), stearic (STEAR) or stearic interesterified (STEAR INTER). Plasma lipids, lipoprotein profile, arterial lesion area, macrophage infiltration, collagen content and inflammatory response modulation were determined. Macrophage cholesterol efflux and the arterial expression of cholesterol uptake and efflux receptors were also performed. The interesterification process did not alter plasma lipid concentrations. Although PALM INTER did not increase plasma cholesterol concentration as much as TRANS, the cholesterol enrichment in the LDL particle was similar in both groups. Moreover, PALM INTER induced the highest IL-1 beta, MCP-1 and IL-6 secretion from peritoneal macrophages as compared to others. This inflammatory response elicited by PALM INTER was confirmed in arterial wall, as compared to PALM. These deleterious effects of PALM INTER culminate in higher atherosclerotic lesion, macrophage infiltration and collagen content than PALM, STEAR, STEAR INTER and PUFA. These events can partially be attributed to a macrophage cholesterol accumulation, promoted by apoAl and HDL2-mediated cholesterol efflux impairment and increased Olr-1 and decreased Abca1 and Nr1h3 expressions in the arterial wall. Interesterified fats containing palmitic acid induce atherosclerosis development by promoting cholesterol accumulation in LDL particles and macrophagic cells, activating the inflammatory process in LDLr-KO mice.
conferenceObject Palmitic Interesterified Fat Induces Atherosclerosis and Inflammatory Cytokine Secretion in LDL Receptor Knockout Mice(2014) AFONSO, Milessa S.; LAVRADOR, Maria Silvia F.; KOIKE, Marcia; BOMBO, Renata P.; NUNES, Valeria S.; CATANOZI, Sergio; CASTILHO, Gabriela; PASSARELLI, Marisa; NAKANDAKARE, Edna R.; LOTTENBERG, Ana Maria- International descriptive and interventional survey for oxycholesterol determination by gas- and liquid-chromatographic methods(2018) LUETJOHANN, Dieter; BJORKHEM, Ingemar; FRIEDRICHS, Silvia; KERKSIEK, Anja; GEILENKEUSER, Wolf-Jochen; LOVGREN-SANDBLOM, Anita; ANSORENA, Diana; ASTIASARAN, Iciar; BAILA-RUEDA, Lucia; BARRIUSO, Blanca; BRETILLON, Lionell; BROWNE, Richard W.; CACCIA, Claudio; CENARRO, Ana; CRICK, Peter J.; FAULER, Guenter; GARCIA-LLATAS, Guadalupe; GRIFFITHS, William J.; IULIANO, Luigi; LAGARDA, Maria Jesus; LEONI, Valerio; LOTTENBERG, Ana Maria; MATYSIK, Silke; MCDONALD, Jeff; RIDEOUT, Todd C.; SCHMITZ, Gerd; NUNES, Valeria Sutti; WANG, Yuqin; ZERBINATI, Chiara; DICZFALUSY, Ulf; SCHOETT, Hans-FriederIncreasing numbers of laboratories develop new methods based on gas-liquid and high-performance liquid chromatography to determine serum concentrations of oxygenated cholesterol metabolites such as 7 alpha-, 24(S)-, and 27-hydroxycholesterol. We initiated a first international descriptive oxycholesterol (OCS) survey in 2013 and a second interventional survey 2014 in order to compare levels of OCS reported by different laboratories and to define possible sources of analytical errors. In 2013 a set of two lyophilized serum pools (A and B) was sent to nine laboratories in different countries for OCS measurement utilizing their own standard stock solutions. In 2014 eleven laboratories were requested to determine OCS concentrations in lyophilized pooled sera (C and D) utilizing the same provided standard stock solutions of OCS. The participating laboratories submitted results obtained after capillary gas-liquid chromatography-mass selective detection with either epicoprostanol or deuterium labelled sterols as internal standards and high-performance liquid chromatography with mass selective detection and deuterated OCS as internal standard. Each participant received a clear overview of the results in form of Youden-Plots and basic statistical evaluation in its used unit. The coefficients of variation of the concentrations obtained by all laboratories using their individual methods were 58.5-73.3% (survey 1), 56.8-60.3% (survey 2); 36.2-35.8% (survey 1), 56.6-59.8, (survey 2); 61.1-197.7% (survey 1), 47.2-74.2% (survey 2) for 24(S)-, 27-, and 7 alpha-hydroxycholesterol, respectively. We are surprised by the very great differences between the laboratories, even under conditions when the same standards were used. The values of OCS's must be evaluated in relation to the analytical technique used, the efficiency of the ample separation and the nature of the internal standard used. Quantification of the calibration solution and inappropriate internal standards could be identified as major causes for the high variance in the reported results from the different laboratories. A harmonisation of analytical standard methods is highly needed. (C) 2018 Published by Elsevier B.V.
- Omega-6 polyunsaturated fatty acids prevent atherosclerosis development in LDLr-KO mice, in spite of displaying a pro-inflammatory profile similar to trans fatty acids(2012) MACHADO, Roberta M.; NAKANDAKARE, Edna R.; QUINTAO, Eder C. R.; CAZITA, Patricia M.; KOIKE, Marcia K.; NUNES, Valeria S.; FERREIRA, Fabiana D.; AFONSO, Milessa S.; BOMBO, Renata P. A.; MACHADO-LIMA, Adriana; SORIANO, Francisco G.; CATANOZI, Sergio; LOTTENBERG, Ana MariaThe development of atherosclerosis and the inflammatory response were investigated in LDLr-KO mice on three high-fat diets (40% energy as fat) for 16 weeks: trans (TRANS), saturated (SAFA) or omega-6 polyunsaturated (PUFA) fats. The following parameters were measured: plasma lipids, aortic root total cholesterol (TC), lesion area (Oil Red-O), ABCA1 content and macrophage infiltration (immunohistochemistry), collagen content (Picrosirius-red) and co-localization of ABCA1 and macrophage (confocal microscopy) besides the plasma inflammatory markers (IL-6, TNF-alpha) and the macrophage inflammatory response to lipopolysaccharide from Escherichia coli (LPS). As expected, plasma TC and TG concentrations were lower on the PUFA diet than on TRANS or SAFA diets. Aortic intima macrophage infiltration, ABCA1 content, and lesion area on PUFA group were lower compared to TRANS and SAFA groups. Macrophages and ABCA1 markers did not co-localize in the atherosclerotic plaque, suggesting that different cell types were responsible for the ABCA1 expression in plaques. Compared to PUFA, TRANS and SAFA presented higher collagen content and necrotic cores in atherosclerotic plaques. In the artery wall, TC was lower on PUFA compared to TRANS group; free cholesterol was lower on PUFA compared to TRANS and SAFA; cholesteryl ester concentration did not vary amongst the groups. Plasma TNF-alpha concentration on PUFA and TRANS-fed mice was higher compared to SAFA. No difference was observed in IL-6 concentration amongst groups. Regarding the macrophage inflammatory response to LPS, TRANS and PUFA presented higher culture medium concentrations of IL-6 and TNF-alpha as compared to SAFA. The PUFA group showed the lowest amount of the anti-inflammatory marker IL-10 compared to TRANS and SAFA groups. In conclusion, PUFA intake prevented atherogenesis, even in a pro-inflammatory condition.
- Dietary phytosterol does not accumulate in the arterial wall and prevents atherosclerosis of LDLr-KO mice(2013) BOMBO, Renata P. A.; AFONSO, Milessa S.; MACHADO, Roberta M.; LAVRADOR, Maria Silvia Ferrari; NUNES, Valeria S.; QUINTAO, Eder R.; KOIKE, Marcia; CATANOZI, Sergio; LIN, Chin Jia; NAKANDAKARE, Edna R.; LOTTENBERG, Ana MariaScope: There have been conflicting reports on the usefulness of phytosterols (PS) in preventing atherosclerosis. We evaluated the effects of dietary PS supplementation in LDLr-KO male mice on the plasma and aorta sterol concentrations and on atherosclerotic lesion development. Methods and results: Mice were fed a high fat diet (40% of energy) supplemented with or without PS (2% w/w, n = 10). Plasma and arterial wall cholesterol and PS concentrations, lesion area, macrophage infiltration, and mRNA expression from LOX-1, CD36, ABCA1 and ABCG1 in peritoneal macrophages were measured. After 16 weeks, the plasma cholesterol concentration in PS mice was lower than that in the controls (p = 0.02) and in the arterial wall (p = 0.03). Plasma PS concentrations were higher in PS-fed animals than in controls (p < 0.0001); however, the arterial wall PS concentration did not differ between groups. The atherosclerotic lesion area in the PS group (n = 5) was smaller than that in controls (p = 0.0062) and the macrophage area (p = 0.0007). PS correlates negatively with arterial lipid content and macrophage (r = -0.76; p < 0.05). PS supplementation induced lower ABCG1 mRNA expression (p < 0.05). Conclusions: Despite inducing an increase in PS plasma concentration, PS supplementation is not associated with its accumulation in the arterial wall and prevents atherosclerotic lesion development.
- Interesterified Fats Induce Deleterious Effects on Adipose Tissue and Liver in LDLr-KO Mice(2019) LAVRADOR, Maria Silvia Ferrari; AFONSO, Milessa Silva; CINTRA, Dennys Esper; KOIKE, Marcia; NUNES, Valeria Sutti; DEMASI, Marina; LIN, Chin Jia; BEDA, Lis Mie Masuzawa; GIOIELLI, Luiz Antonio; BOMBO, Renata de Paula Assis; MACHADO, Roberta Marcondes; CATANOZI, Sergio; NAKANDAKARE, Edna Regina; LOTTENBERG, Ana MariaInteresterified fats are being widely used by the food industry in an attempt to replace trans fatty acids. The effect of interesterified fats containing palmitic or stearic acids on lipid metabolism and inflammatory signaling pathways in adipose and hepatic tissues was evaluated. Male LDLr-KO mice were fed a high-fat diet containing polyunsaturated (PUFA), palmitic (PALM), palmitic interesterified (PALM INTER), stearic (STEAR), or stearic interesterified (STEAR INTER) fats for 16 weeks. The expression of genes and protein levels involved in lipid metabolism and inflammatory processes in liver and white adipose tissue was determined by quantitative RT-PCR and by Western blot, respectively. The infiltration of inflammatory cells in hepatic and adipose tissues was determined by eosin and hematoxylin, while liver collagen content was determined by Sirius Red staining. Both interesterified fats increased liver collagen content and JNK phosphorylation. Additionally, the STEAR INTER group developed nonalcoholic steatohepatitis (NASH) associated with higher neutrophil infiltration. PALM INTER induced adipose tissue expansion and enlargement of adipocytes. Furthermore, PALM INTER triggered increased IKK phosphorylation and TNF protein content, conditions associated with the upstream activation of the NFkB signaling pathway. STEAR INTER induced NASH, while PALM INTER triggered hepatic fibrosis and adipocyte hypertrophy with inflammatory response in LDLr-KO mice.
- Dietary interesterified fat enriched with palmitic acid induces atherosclerosis by impairing macrophage cholesterol efflux and eliciting inflammation (vol 32C, pg 91, 2016)(2016) AFONSO, Milessa Silva; LAVRADOR, Maria Silvia Ferrari; KOIKE, Marcia Kiyomi; CINTRA, Dennys Esper; FERREIRA, Fabiana Dias; NUNES, Valeria Sutti; CASTILHO, Gabriela; GIOIELLI, Luiz Antonio; BOMBO, Renata Paula; CATANOZI, Sergio; CALDINI, Elia Garcia; DAMACENO-RODRIGUES, Nilsa Regina; PASSARELLI, Marisa; NAKANDAKARE, Edna Regina; LOTTENBERG, Ana Maria
- First international descriptive and interventional survey for cholesterol and non-cholesterol sterol determination by gas- and liquid-chromatography-Urgent need for harmonisation of analytical methods(2019) LUETJOHANN, Dieter; BJORKHEM, Ingemar; FRIEDRICHS, Silvia; KERKSIEK, Anja; LOVGREN-SANDBLOM, Anita; GEILENKEUSER, Wolf-Jochen; AHRENDS, Robert; ANDRADE, Isabel; ANSORENA, Diana; ASTIASARAN, Iciar; BAILA-RUEDA, Lucia; BARRIUSO, Bianca; BECKER, Susen; BRETILLON, Lionel; BROWNE, Richard W.; CACCIA, Claudio; CEGLAREK, Uta H.; CENARRO, Ana; CRICK, Peter J.; FAULER, Guenter; GARCIA-LLATAS, Guadalupe; GRAY, Robert; GRIFFITHS, William J.; GYLLING, Helena; HARDING, Scott; HELMSCHRODT, Christin; IULIANO, Luigi; JANSSEN, Hans-Gerd; JONES, Peter; KAIPIAINEN, Leena; KANNENBERG, Frank; LAGARDA, Maria Jesus; LEONI, Valerio; LOTTENBERG, Ana Maria; MACKAY, Dylan S.; MATYSIK, Silke; MCDONALD, Jeff; MENENDEZ-CARRENO, Maria; MYRIE, Semone B.; NUNES, Valeria Sutti; OSTLUND, Richard E.; POLISECKI, Eliana; RAMOS, Fernando; RIDEOUT, Todd C.; SCHAEFER, Ernst J.; SCHMITZ, Gerd; WANG, Yuqin; ZERBINATI, Chiara; DICZFALUSY, Ulf; SCHOETT, Hans-FriederSerum concentrations of lathosterol, the plant sterols campesterol and sitosterol and the cholesterol metabolite 5 alpha-cholestanol are widely used as surrogate markers of cholesterol synthesis and absorption, respectively. Increasing numbers of laboratories utilize a broad spectrum of well-established and recently developed methods for the determination of cholesterol and non-cholesterol sterols (NCS). In order to evaluate the quality of these measurements and to identify possible sources of analytical errors our group initiated the first international survey for cholesterol and NCS. The cholesterol and NCS survey was structured as a two-part survey which took place in the years 2013 and 2014. The first survey part was designed as descriptive, providing information about the variation of reported results from different laboratories. A set of two lyophilized pooled sera (A and B) was sent to twenty laboratories specialized in chromatographic lipid analysis. The different sterols were quantified either by gas chromatography-flame ionization detection, gas chromatography- or liquid chromatography-mass selective detection. The participants were requested to determine cholesterol and NCS concentrations in the provided samples as part of their normal laboratory routine. The second part was designed as interventional survey. Twenty-two laboratories agreed to participate and received again two different lyophilized pooled sera (C and D). In contrast to the first international survey, each participant received standard stock solutions with defined concentrations of cholesterol and NCS. The participants were requested to use diluted calibration solutions from the provided standard stock solutions for quantification of cholesterol and NCS. In both surveys, each laboratory used its own internal standard (5 alpha-cholestane, epicoprostanol or deuterium labelled sterols). Main outcome of the survey was, that unacceptably high interlaboratory variations for cholesterol and NCS concentrations are reported, even when the individual laboratories used the same calibration material. We discuss different sources of errors and recommend all laboratories analysing cholesterol and NCS to participate in regular quality control programs.
conferenceObject Interesterified Fats Induce Nonalcoholic Steatohepatitis or Enhance the Adipose Tissue and Adipocyte Hypertrophy(2014) LAVRADOR, Maria Silvia F.; AFONSO, Milessa S.; KOIKE, Marcia; BOMBO, Renata P.; CINTRA, Dennys E.; NUNES, Valeria S.; CATANOZI, Sergio; NAKANDAKARE, Edna R.; LOTTENBERG, Ana Maria- Plasma lathosterol measures rates of cholesterol synthesis and efficiency of dietary phytosterols in reducing the plasma cholesterol concentration(2022) NUNES, Valeria Sutti; ILHA, Angela de Oliveira Godoy; FERREIRA, Guilherme da Silva; BOMBO, Renata de Paula Assis; AFONSO, Milessa Silva; LAVRADOR, Maria Silvia Ferrari; MACHADO, Roberta Marcondes; NAKANDAKARE, Edna Regina; QUINTA, Eder Carlos Rocha; LOTTENBERG, Ana MariaObjectives: Because the plasma campesterol/cholesterol ratio does not differ between groups that absorb different amounts of cholesterol, the authors investigated whether the plasma Phytosterols (PS) relate to the body's cholesterol synthesis rate measured as non-cholesterol sterol precursors (lathosterol). Method: The authors studied 38 non-obese volunteers (58 +/- 12 years; Low-Density Lipoprotein Cholesterol - LDLC >= 130 mg/dL) randomly assigned to consume 400 mL/day of soy milk (Control phase) or soy milk + PS (1.6 g/ day) for four weeks in a double-blind, cross-over study. PS and lathosterol were measured in plasma by gas chromatography coupled to mass spectrophotometry. Results: PS treatment reduced plasma total cholesterol concentration (-5.5%, p < 0.001), LDL-C (-7.6%, p < 0.001), triglycerides (-13.6%, p < 0.0085), and apolipoprotein B (apo B) (-6.3%, p < 0.008), without changing high density lipoprotein cholesterol (HDL-C concentration), but plasma lathosterol, campesterol and sitosterol expressed per plasma cholesterol increased. Conclusions: The lathosterol-to-cholesterol plasma ratio predicted the plasma cholesterol response to PS feeding. The highest plasma lathosterol concentration during the control phase was associated with a lack of response of plasma cholesterol during the PS treatment period. Consequently, cholesterol synthesis in non-responders to dietary PS being elevated in the control phase indicates these cases resist to further synthesis rise, whereas responders to dietary PS, having in the control phase synthesis values lower than non-responders, expand synthesis on alimentary PS. Responders absorb more PS than non-responders, likely resulting from responders delivering into the intestinal lumen less endogenous cholesterol than non-responders do, thus facilitating greater intestinal absorption of PS shown as increased plasma PS concentration.