Browsing by Author "Busso, Dolores"
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- ItemA Quinoa Protein Hydrolysate Fractionated by Electrodialysis with Ultrafiltration Membranes Improves Maternal and Fetal Outcomes in a Mouse Model of Gestational Diabetes Mellitus(2023) Busso, Dolores; Gonzalez, Adrian; Santander, Nicolas; Saavedra, Fujiko; Quiroz, Alonso; Rivera, Katherine; Gonzalez, Javier; Olmos, Pablo; Marette, Andre; Bazinet, Laurent; Illanes, Sebastian; Enrione, JavierScopeQuinoa intake exerts hypoglycemic and hypolipidemic effects in animals and humans. Although peptides from quinoa inhibit key enzymes involved in glucose homeostasis in vitro, their in vivo antidiabetic properties have not been investigated.Methods and resultsThis study evaluated the effect of oral administration of a quinoa protein hydrolysate (QH) produced through enzymatic hydrolysis and fractionation by electrodialysis with ultrafiltration membrane (EDUF) (FQH) on the metabolic and pregnancy outcomes of Lepdb/+ pregnant mice, a preclinical model of gestational diabetes mellitus. The 4-week pregestational consumption of 2.5 mg mL-1 of QH in water prevented glucose intolerance and improves hepatic insulin signaling in dams, also reducing fetal weights. Sequencing and bioinformatic analyses of the defatted FQH (FQHD) identified 11 peptides 6-10 amino acids long that aligned with the quinoa proteome and exhibited putative anti-dipeptidyl peptidase-4 (DPP-IV) activity, confirmed in vitro in QH, FQH, and FDQH fractions. Peptides homologous to mouse and human proteins enriched for biological processes related to glucose metabolism are also identified.ConclusionProcessing of quinoa protein may be used to develop a safe and effective nutritional intervention to control glucose intolerance during pregnancy. Further studies are required to confirm if this nutritional intervention is applicable to pregnant women.
- ItemAdvances in the physiological and pathological implications of cholesterol(2013) Cortés Mora, Víctor Antonio; Busso, Dolores; Mardones, Pablo; Maiz Gurruchaga, Manuel Alberto; Arteaga Ll., Antonio; Nervi, Flavio; Rigotti Rivera, Attilio
- ItemApolipoprotein A-I deficiency does not affect biliary lipid secretion and gallstone formation in mice(2011) Amigo Boker, Ludwig Peter; Quiñones, Verónica; Leiva Mendoza, Andrea Alejandra; Busso, Dolores; Zanlungo Matsuhiro, Silvana; Nervi, Flavio; Rigotti Rivera, Attilio
- ItemAttenuation of atherogenic apo B-48-dependent hyperlipidemia and high density lipoprotein remodeling induced by vitamin C and E combination and their beneficial effect on lethal ischemic heart disease in mice(2018) Contreras-Duarte, Susana; Chen, P.; Andía Kohnenkampf, Marcelo Edgardo; Uribe Arancibia, Sergio A.; Irarrázaval Mena, Pablo; Kopp, S.; Kern, S.; Marsche, G.; Busso, Dolores; Rigotti Rivera, AttilioAbstract Background and aims Atherosclerotic cardiovascular disease is highly prevalent and its underlying pathogenesis involves dyslipidemia including pro-atherogenic high density lipoprotein (HDL) remodeling. Vitamins C and E have been proposed as atheroprotective agents for cardiovascular disease management. However, their effects and benefits on high density lipoprotein function and remodeling are unknown. In this study, we evaluated the role of vitamin C and E on non HDL lipoproteins as well as HDL function and remodeling, along with their effects on inflammation/oxidation biomarkers and atherosclerosis in atherogenic diet-fed SR-B1 KO/ApoER61h/h mice. Methods and results: Mice were pre-treated for 5 weeks before and during atherogenic diet feeding with vitamin C and E added to water and diet, respectively. Compared to a control group, combined vitamin C and E administration reduced serum total cholesterol and triglyceride levels by decreasing apo B-48-containing lipoproteins, remodeled HDL particles by reducing phospholipid as well as increasing PON1 and apo D content, and diminished PLTP activity and levels. Vitamin supplementation improved HDL antioxidant function and lowered serum TNF-α levels. Vitamin C and E combination attenuated atherogenesis and increased lifespan in atherogenic diet-fed SR-B1 KO/ApoER61h/h mice. Conclusions Vitamin C and E administration showed significant lipid metabolism regulating effects, including HDL remodeling and decreased levels of apoB-containing lipoproteins, in mice. In addition, this vitamin supplementation generated a cardioprotective effect in a murine model of severe and lethal atherosclerotic ischemic heart disease.
- ItemContribución de la provisión materna de vitamina E a la regulación del balance rédox y la prevención del daño oxidativo durante el cierre del tubo neural en ratón(2022) Quiroz Vallverdú, Alonso Ingmar; Busso, Dolores; Pontificia Universidad Católica de Chile. Facultad de MedicinaLos defectos en el cierre del tubo neural (NTD) corresponden a un grupo de malformaciones congénitas del tubo neural, estructura formada durante el desarrollo embrionario temprano que da origen al cerebro y la médula espinal. Entre los factores no genéticos involucrados en la etiología del NTD se encuentran alteraciones metabólicas de la madre y el consumo inadecuado de algunos micronutrientes, como el folato o vitamina B9. En humanos, la obesidad materna y la diabetes han sido reconocidas como factores de riesgo de NTD y se ha propuesto que el estrés oxidativo asociado a estas condiciones interfiere con el cierre del tubo neural. En los últimos años, nuestro laboratorio reportó que cerca del 30-50% de los embriones deficientes para la proteína Scavenger Receptor Class B Type I (SR-B1 KO), el principal receptor de lipoproteínas de alta densidad (HDL), presentan NTD anterior que progresa a anencefalia. Durante el desarrollo temprano, SR-B1 es expresado en tejidos extraembrionarios, específicamente en los trofoblastos gigantes que componen el saco vitelino parietal (pYS). Los embriones SRB1 KO presentan mayores niveles de especies reactivas del oxígeno (ROS) y contienen menos vitamina E que los embriones SR-B1 silvestres o wild type (WT), sugiriendo que SR-B1 participa en la provisión materna de la vitamina E al embrión. La suplementación materna con α-tocoferol, principal isómero de la vitamina E, previene completamente la incidencia de NTD y normaliza los niveles de ROS en los embriones SR-B1 KO, sugiriendo que el daño oxidativo pudiera contribuir a la etiología de los NTD en este modelo. El α-tocoferol es un antioxidante liposoluble que, coordinadamente con el sistema antioxidante endógeno, detiene la reacción en cadena de la peroxidación lipídica, protegiendo a los lípidos del daño oxidativo. En especial, esta vitamina preservaría los ácidos grasos poliinsaturados (PUFAs), lípidos esenciales para el desarrollo embrionario. En la primera parte de esta tesis, evaluamos el status oxidativo en embriones WT, SR-B1 KO normales y SR-B1 KO con NTD mediante la determinación de los niveles de algunas moléculas antioxidantes endógenas y de un marcador de lipoperoxidación. Adicionalmente, caracterizamos las abundancias relativas de PUFAs en fosfolípidos y otros lípidos en los respectivos grupos embrionarios usando la tecnología de shotgun lipidomics. Los resultados obtenidos no mostraron una alteración del sistema antioxidante endogéno en los embriones SR-B1 KO, pero sí un aumento de la lipoperoxidación. Ni los niveles de vitamina E embrionaria ni la peroxidación lipídica se previnieron al suplementar a las madres con una dieta enriquecida con vitamina E. En conjunto, estos resultados sugieren que el mecanismo de acción de la vitamina E en la prevención de los NTD en embriones SR-B1 KO estaría mediado por un efecto no sobre el embrión mismo, sino indirecto y mediado por el pYS. Sin embargo, el análisis mediante WB de vías de señalización asociadas a la producción de ROS extracelular en el pYS no mostró diferencias entre tejidos de preñeces con o sin la intervención con vitamina E. Si bien el rol de dicho tejido embrionario en la prevención de NTD mediada por vitamina E no pudo ser demostrado, es posible que otras vías o procesos indirectos, no analizados en esta tesis, expliquen dicho efecto. A través del análisis de lipidómica observamos que la deficiencia de SR-B1 se asoció a niveles disminuidos de PUFAs de cadena larga (LCPUFAs), así como de ácidos grasos monoinsaturados (MUFAs) en determinados fosfolípidos y niveles aumentados de lisofosfatidilcolina (LPC), lo cual sugiere la hidrólisis aumentada de lípidos de membrana. Un resultado inesperado de este estudio fue que los embriones SR-B1 KO con NTD exhibieron acumulación de triglicéridos (TG), lo que indicaría movilización de ácidos grasos desde la membrana a gotas lipídicas. Este mecanismo adaptativo se ha observado previamente en células gliales y cancerígenas para proteger a los lípidos de la oxidación y/o la inflamación. Teniendo en cuenta que la obesidad generalmente cursa con un mayor estado oxidativo en humanos y animales, en la segunda parte de esta tesis hipotetizamos que el consumo de una dieta rica en grasas y azúcares (“high fat/high sugar”, HFHS) en ratonas SR-B1 heterocigotas reduciría la provisión embrionaria de vitamina E y aumentaría la incidencia de NTD debido a un aumento en los requerimientos antioxidantes maternos. Tal como esperábamos, la dieta HFHS indujo una alteración en el metabolismo materno de la glucosa y los lípidos, y aumentó la incidencia de NTD en los embriones KO y heterocigotos, y también se asoció a la ocurrencia de NTD en embriones WT. Además, la alimentación de las ratonas con esta dieta provocó retardo del desarrollo de los embriones, de manera independiente del genotipo de SR-B1. Los efectos teratogénicos de la dieta no fueron mediados por una reducción en los niveles de la vitamina E en plasma materno ni tampoco observamos un aumento en el daño oxidativo en madres o embriones de gestaciones del grupo HFHS. Interesantemente, mientras que las hembras alimentadas con la dieta HFHS presentaron intolerancia a la glucosa, mayores niveles de péptido C plasmático, hipercolesterolemia y acumulación de colesterol en hígado y pYS, la suplementación con vitamina E en ratonas del grupo HFHS previno la incidencia de NTD y el retardo del desarrollo, y corrigió todas las anormalidades metabólicas maternas mencionadas. Estos resultados sugieren que la vitamina E podría ejercer un efecto protector sobre el metabolismo materno, con potenciales ventajas sobre el embrión. En conjunto, los resultados obtenidos en esta tesis sugieren que la vitamina podría prevenir los NTD a través de los siguientes mecanismos: I) manteniendo los niveles adecuados de PUFAs en fosfolípidos en el embrión en desarrollo, posiblemente mediante mecanismos no-antioxidantes, y II) en hembras consumiendo una dieta obesogénica, previniendo las perturbaciones metabólicas maternas en glúcidos y lípidos. Estos resultados confirman que la vitamina E y los PUFAs son moléculas relevantes para el cierre del tubo neural. Por lo tanto, la adecuación de la ingesta de estos lípidos podría servir como estrategia para prevenir los NTD, especialmente en condiciones como la obesidad, diabetes o dislipidemias.
- ItemCurrent folate status in Chilean women of childbearing age: findings from the 2016-2017 National Health Survey(2019) Busso, Dolores; Echeverria, Guadalupe; Morales, Fernanda; Farias, Marcelo; Margozzini, PaulaIntroduction: Mandatory folic acid (FA) fortification is an effective policy to ensure adequate preconceptional serum folate (SF) levels in women and to reduce the incidence of neural tube defects (NTD). In Chile, FA fortification of wheat flour started in 2000 and significantly reduced NTD prevalence. In 2010, 1:2 Chileans over 65 years old had supraphysiological SF levels. In 2012, FA fortification was reduced from 2.2 to 1.8 mg FA/kg flour. Considering the epidemiological transition in Chile over the last decades and the adjustment of the FA fortification policy in 2012, this study was aimed at describing the current SF levels in women of reproductive age in our country. Methods: 225 women (15-49 years) who participated in the Chilean National Health Survey (NHS) 2016-17 were included in this analysis. NHS 2016-17 used stratified multistage sampling. SF levels were determined by electrochemiluminescence immunoassay, and defined as deficient (≤4.4 ng/ml), normal (4.41 to 20 ng/ml) and supraphysiological [three subcategories: high (20.01 to 25.6 ng/ml), very high (25.61 to 29 ng/ml) and highest (>29 ng/ml)]. Multiple logistic regression analyses were performed using SPSS software (version 17.0). Results: The proportions of women in each decade of life were representative of the national proportions. More than 99% of the women came from urban areas, and near 91% had medium or high educational level. Only 32% of the women declared being current smokers, and 88% declared they were sedentary. Almost 70% of subjects were either overweight or obese, reflecting the current nutritional status of the Chilean population. The SF mean ± SE, median and range were 14.20 ± 0.39, 13.52 and 2.10 - 32.22 ng/ml, respectively. Folate deficiency was present in 0.9% of the women studied, while 7% had supraphysiological levels of the vitamin (3.7% high, 1.6% very high and 1.7% highest levels). Multivariate analyses using linear regression did not show that age, educational level, marital status, parity, smoker/non-smoker or nutritional status had significant effects on FS levels. Conclusion: Folate deficiency in women of reproductive age living in the Metropolitan Region is almost inexistent according to the NHS 2016- 17, showing that most Chilean women are protected from NTD due to folate deficiency. Supraphysiological SF levels were found in 7% of the studied population, lower than the 50% determined in elderly subjects in 2010. Specific policies to reduce the proportion of Chileans at high risk of SF deficiency or excess, in combination with surveillance of FA fortification in flour mills, may help to avoid potential unintended effects of FA fortification in this country. Funding: Chilean Ministry of Health and Pontificia Universidad Católica de Chile.
- ItemDeficient Vitamin E Uptake During Development Impairs Neural Tube Closure in Mice Lacking Lipoprotein Receptor SR-BI(2017) Santander Grez, Nicolás Guillermo; Lizama, Carlos; Parga Ponce, María José; Quiroz Vallverdu, Alonso Ingmar; Pérez Pons, Druso Diego; Echeverría Errázuriz, Guadalupe; Ulloa, Lorena; Palma, Verónica; Rigotti Rivera, Attilio; Busso, Dolores
- ItemDevelopmental abnormalities in mouse embryos lacking the HDL receptor SR-BI(2013) Santander, Nicolás Guillermo; Contreras Duarte, Susana de las Mercedes; Awad, María Fernanda; Lizama, Carlos; Passalacqua, Isabella; Rigotti Rivera, Attilio; Busso, Dolores
- ItemDisfuncionalidad antioxidante de las lipoproteínas de alta densidad (HDL) en pacientes diabéticos descompensados(2015) Awad, Fernanda; Contreras Duarte, Susana de las Mercedes; Molina, Patricia; Quiñones, Verónica; Serrano, V.; Abbott Cáceres, Eduardo Francisco; Maiz, Alberto; Busso, Dolores; Rigotti Rivera, Attilio
- ItemEarly Onset Intrauterine Growth Restriction in a Mouse Model of Gestational Hypercholesterolemia and Atherosclerosis(2014) Busso, Dolores; Mascareno, L.; Salas, F.; Berkowitz Fiebich, Loni; Santander, N.; Quiroz Vallverdu, Alonso Ingmar; Amigo Boker, Ludwig Peter; Valdés Stromilli, Gloria; Rigotti Rivera, Attilio
- ItemExcess cholesterol induces mouse egg activation and may cause female infertility(2014) Yesilaltay, A.; Busso, Dolores; Quilaqueo Iturrieta, Linda Lien-Ale.; Orellana Roca, Juan Andrés
- ItemFertilization Induces a Transient Exposure of Phosphatidylserine in Mouse Eggs(2013) Curia, Claudio A.; Ernesto, Juan I.; Stein, Paula; Busso, Dolores; Schultz, Richard M.; Cuasnicu, Patricia S.; Cohen, Débora J.
- ItemFolate status in women of childbearing age in the Urban Metropolitan Region of Chile: results from the National Health Survey 2016-2017(CAMBRIDGE UNIV PRESS, 2021) Busso, Dolores; Echeverria, Guadalupe; Passi Solar, Alvaro; Morales, Fernanda; Farias, Marcelo; Margozzini, PaulaObjective: To analyse serum folate levels in women of childbearing age in the Metropolitan Region (MR) of Chile.
- ItemGugulipid causes hypercholesterolemia leading to endothelial dysfunction, increased atherosclerosis, and premature death by ischemic heart disease in male mice.(2017) Contreras Duarte, Susana de las Mercedes; Leiva Mendoza, Andrea Alejandra; Amigo, Ludwig; Sepulveda, Esteban; Boric P., Mauricio; Quinones, Veronica; Busso, Dolores; Rigotti Rivera, Attilio
- ItemHigh density lipoprotein cholesterol and proteome in SR-B1 KO mice: lost in precipitation(2018) Contreras Duarte, Susana de las Mercedes; Santander Grez, Nicolás Guillermo; Rigotti Rivera, Attilio; Busso, Dolores; Birner-Gruenberger, Ruth.; Wadsack, Christian.Abstract Scavenger receptor class B type 1 (SR-B1) plays an essential role in high density lipoprotein (HDL) metabolism. SR-B1 deficient (SR-B1 KO) mice are prone to atherosclerosis and exhibit abnormally large, cholesterol-rich, dysfunctional HDL. In a recent issue of J Transl Med, Cao et al. described results of proteomics analyses of HDL isolated from wild-type (WT) and SR-B1 KO mice using precipitation of large lipoproteins with polyethylene glycol (PEG). They report abnormalities in SR-B1 KO HDL protein components that correlate with HDL function. In this commentary, we describe and discuss the differences in the results published by Cao et al. and those obtained in a recent study from our laboratory using shotgun proteomics of HDL of SR-B1 KO mice isolated by ultracentrifugation. We propose that different HDL purification procedures used may account for the discrepancies observed. We show that SR-B1 KO HDL purification using either PEG or dextran sulfate precipitation results in enrichment of small HDL subclasses, and may therefore underestimate alterations in lipoprotein composition or function. Compared to HDL obtained by ultracentrifugation, HDL isolated by PEG precipitation show a lower ApoE/ApoA-I proportion and reduced cholesterol content. HDL protein components described by Cao et al. or our laboratory are mostly inconsistent: only 33 HDL proteins were detected in both datasets, whereas a significant number of proteins were only identified by Cao et al. (n = 43) or Contreras-Duarte et al. (n = 26) datasets. The relative abundance of HDL-associated peptide and protein levels in WT vs SR-B1 HDL were also highly different in both datasets. This study indicates that caution must be taken when interpreting results from HDL isolated by chemical precipitation.
- ItemLa hipótesis de Pedersen no es suficiente : otros nutrientes además de la glucosa explicarían la macrosomía fetal en pacientes diabéticas gestacionales con sobrepeso y buen control glicémico(2013) Olmos Coelho, Pablo Roberto; Martelo, G.; Reimer, V.; Rigotti Rivera, Attilio; Busso, Dolores; Belmar Jones, Cristián Gastón; González Pérez, Rogelio Iván; Goldenberg, D.; Samith Catalán, Bárbara Patricia; Santos Martín, José Luis; Escalona, M.; Quezada, T.; Faundez, J.; Nicklitschek, I.
- ItemHuman fertilization : Epididymal hCRISP1 mediates sperm-zona pellucida binding through its interaction with ZP3(2014) Maldera, J.; Munoz, M.; Chirinos, M.; Busso, Dolores; Raffo, F.; Battistone, M.; Blaquier, J.; Larrea, F.; Cuasnicu, P.
- ItemIntake of red wine grape pomace decreased atherosclerosis, attenuated myocardial damage and increased survival in a murine model of lethal coronary heart disease(MDPI, 2019) Salas Perez, Francisca Lorena; Rivera Vega, Katherine Solange; Echeverria, Guadalupe; Urquiaga, Ines; Dicenta, Sara; Perez, Druso; Andia, Marcelo; Uribe, Sergio; Tejos, Cristian; Busso, Dolores; Irarrazaval Mena, Pablo; Rigotti, Attilio
- ItemIntake of Vitamin E and C in Women of Reproductive Age: Results from the Latin American Study of Nutrition and Health (ELANS)(2021) Busso, Dolores; David, Andrea; Penailillo, Reyna; Echeverria, Guadalupe; Rigotti, Attilio; Kovalskys, Irina; Gomez, Georgina; Cortes Sanabria, Lilia Yadira; Yepez Garcia, Martha Cecilia; Pareja, Rossina G.; Herrera-Cuenca, Marianella; Fisberg, MauroVitamin E was identified as a lipophilic compound essential to maintain rat pregnancy. Low vitamin E intake during early pregnancy associates with congenital malformations and embryonic loss in animals and with miscarriage and intrauterine growth restriction in humans. Vitamin E protects cell membranes from lipoperoxidation and exerts non-antioxidant activities. Its function can be restored by vitamin C; thus, intake and circulating levels of both micronutrients are frequently analyzed together. Although substantial vitamin E inadequacy was reported worldwide, its consumption in Latin America (LatAm) is mostly unknown. Using data from the Latin American Study of Nutrition and Health (Estudio Latinoamericano de Nutricion y Salud, ELANS), we evaluated vitamin E and C intake in women of reproductive age (WRA) from eight LatAm countries and identified their main food sources. Two non-consecutive 24-h dietary recalls in 3704 women aged from 15 to 49 years and living in urban locations showed low average intake of vitamin E (7.9 mg/day vs. estimated average requirement (EAR) of 12 mg/day) and adequate overall vitamin C consumption (95.5 mg/day vs. EAR of 60 mg/day). The mean regional inadequacy was 89.6% for vitamin E and 36.3% for vitamin C. The primary food sources of vitamin E were fats and oils, as well as vegetables. Vitamin C intake was explained mainly by the consumption of fruit juices, fruits, and vegetables. Combined deficient intake of both vitamins was observed in 33.7% of LatAm women. Although the implications of low antioxidant vitamins' consumption in WRA are still unclear, the combined deficient intake of both vitamins observed in one-third of ELANS participants underscores the need for further research on this topic.