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1.
Int J Mol Sci ; 23(19)2022 Oct 09.
Artículo en Inglés | MEDLINE | ID: mdl-36233298

RESUMEN

BACKGROUND: Increased cholesterol absorption and reduced synthesis are processes that have been associated with cardiovascular disease risk in a controversial way. However, most of the studies involving markers of cholesterol synthesis and absorption include conditions, such as obesity, diabetes, dyslipidemia, which can be confounding factors. The present study aimed at investigating the relationships of plasma cholesterol synthesis and absorption markers with cardiovascular disease (CVD) risk factors, cIMT (carotid intima-media thickness), and the presence of carotid plaques in asymptomatic subjects. METHODS: A cross-sectional study was carried out in 270 asymptomatic individuals and anthropometrical parameters, fasting plasma lipids, glucometabolic profiles, high-sensitivity C-reactive protein (hs-CRP), markers of cholesterol synthesis (desmosterol and lathosterol), absorption (campesterol and sitosterol), cIMT, and the presence of atherosclerotic plaques were analyzed. RESULTS: Among the selected subjects aged between 19 and 75 years, 51% were females. Age, body mass index, systolic and diastolic blood pressure, total cholesterol, non-HDL-C, triglycerides, glucose, and lathosterol/sitosterol ratios correlated positively with cIMT (p ≤ 0.05). Atherosclerotic plaques were present in 19% of the subjects. A direct association of carotid plaques with campesterol, OR = 1.71 (95% CI = 1.04-2.82, p ≤ 0.05) and inverse associations with both ratios lathosterol/campesterol, OR = 0.29 (CI = 0.11-0.80, p ≤ 0.05) and lathosterol/sitosterol, OR = 0.45 (CI = 0.22-0.95, p ≤ 0.05) were observed in univariate logistic regression analysis. CONCLUSIONS: The findings suggested that campesterol may be associated with atherosclerotic plaques and the lathosterol/campesterol or sitosterol ratios suggested an inverse association. Furthermore, synthesis and absorption of cholesterol are inverse processes, and the absorption marker, campesterol, may reflect changes in body cholesterol homeostasis with atherogenic potential.


Asunto(s)
Enfermedades Cardiovasculares , Fitosteroles , Placa Aterosclerótica , Adulto , Anciano , Biomarcadores/metabolismo , Proteína C-Reactiva , Grosor Intima-Media Carotídeo , Colesterol/análogos & derivados , Colesterol/metabolismo , Estudios Transversales , Desmosterol , Femenino , Glucosa , Humanos , Masculino , Persona de Mediana Edad , Sitoesteroles , Triglicéridos , Adulto Joven
2.
J Bioenerg Biomembr ; 51(2): 131-136, 2019 04.
Artículo en Inglés | MEDLINE | ID: mdl-30739226

RESUMEN

Phytosterol metabolism is unknown in the hypercholesterolemia of genetic origin. We investigated the metabolism of phytosterols in a cholesterol-free, phytosterol-containing standard diet in hypercholesterolemic mice knockouts for low density lipoprotein receptor (LDLR) and apolipoprotein E (apoE) mice compared to wild-type mice (controls). Phytosterols were measured in mice tissues by GCMS. ApoE-KO mice absorbed less phytosterols than LDLR-KO and the latter absorbed less phytosterols than control mice, because the intestinal campesterol content was low in both KO mice, and sitosterol was low in the intestine in apoE-KO mice as compared to LDLR-KO mice. Although the diet contained nine times more sitosterol than campesterol, the concentration of sitosterol was lower than that of campesterol in plasma in LDLR-KO, and in the liver in controls and in LDLR-KO, but only in apoE-KO. On the other hand, in the intestine sitosterol was higher than campesterol in controls, and in LDLR-KO but with a tendency only in apoE-KO. Because of the high dietary supply of sitosterol, sitosterol was better taken up by the intestine than campesterol, but the amount of sitosterol was lower than that of campesterol in the liver, while in the whole body the amounts of these phytosterols do not differ from each other. Therefore, via intestinal lymph less sitosterol than campesterol was transferred to the body. However, as compared to controls, in apoE-KO mice, but not in LDLR-KO mice, the increase in campesterol and sitosterol in plasma and in the whole body indicating that apoE-KO mice have a marked defect in the elimination of both phytosterols from the body.


Asunto(s)
Alimentación Animal , Colesterol/análogos & derivados , Hígado/metabolismo , Fitosteroles , Receptores de LDL/deficiencia , Sitoesteroles , Animales , Colesterol/farmacocinética , Colesterol/farmacología , Hígado/patología , Ratones , Ratones Noqueados para ApoE , Fitosteroles/farmacocinética , Fitosteroles/farmacología , Receptores de LDL/metabolismo , Sitoesteroles/farmacocinética , Sitoesteroles/farmacología , Especificidad de la Especie
3.
J Bioenerg Biomembr ; 50(4): 283-287, 2018 08.
Artículo en Inglés | MEDLINE | ID: mdl-29675736

RESUMEN

Apolipoprotein E knockout (apoE-KO) mice present synaptic loss, cognitive dysfunction, and high plasma lipid levels that may affect brain function simulating Alzheimer disease. Plasma and brain sterols were measured in apoE-KO and in wild type control mice on a cholesterol-free, phytosterol-containing diet by gas chromatography coupled to a mass spectrometer. Plasma cholesterol and phytosterols (campesterol and sitosterol) were higher in apoE-KO compared to control mice. Cholesterol precursors (desmosterol and lathosterol) were not detected in plasma of control mice but were present in apoE-KO mice. In the brain amounts of cholesterol, desmosterol, campesterol and 24-hydroxycholesterol were significantly lower in apoE-KO than in controls. There is a tendency in apoE-KO for lower values of 7α-hydroxycholesterol and 7ß-hydroxycholesterol. Cholesterol content, synthesis rates (desmosterol) and export of 24-hydroxycholesterol are reduced in the brain of the severe hypercholesterolemic apoE-KO mice.


Asunto(s)
Apolipoproteínas E/deficiencia , Encéfalo/metabolismo , Colesterol/metabolismo , Enfermedad de Alzheimer , Animales , Apolipoproteínas E/genética , Transporte Biológico , Colesterol/análogos & derivados , Colesterol/biosíntesis , Colesterol/sangre , Hidroxicolesteroles/sangre , Ratones , Ratones Noqueados , Fitosteroles/sangre
4.
Mediators Inflamm ; 2016: 1784014, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-27293313

RESUMEN

Sepsis is a systemic inflammatory response to infection eliciting high mortality rate which is a serious health problem. Despite numerous studies seeking for therapeutic alternatives, the mechanisms involved in this disease remain elusive. In this study we evaluated the influence of cholesteryl ester transfer protein (CETP), a glycoprotein that promotes the transfer of lipids between lipoproteins, on the inflammatory response in mice. Human CETP transgenic mice were compared to control mice (wild type, WT) after polymicrobial sepsis induced by cecal ligation and puncture (CLP), aiming at investigating their survival rate and inflammatory profiles. Macrophages from the peritoneal cavity were stimulated with LPS in the presence or absence of recombinant CETP for phenotypic and functional studies. In comparison to WT mice, CETP mice showed higher survival rate, lower IL-6 plasma concentration, and decreased liver toll-like receptor 4 (TLR4) and acyloxyacyl hydrolase (AOAH) protein. Moreover, macrophages from WT mice to which recombinant human CETP was added decreased LPS uptake, TLR4 expression, NF-κB activation and IL-6 secretion. This raises the possibility for new therapeutic tools in sepsis while suggesting that lowering CETP by pharmacological inhibitors should be inconvenient in the context of sepsis and infectious diseases.


Asunto(s)
Proteínas de Transferencia de Ésteres de Colesterol/uso terapéutico , Inflamación/tratamiento farmacológico , Sepsis/tratamiento farmacológico , Receptor Toll-Like 4/metabolismo , Animales , Hidrolasas de Éster Carboxílico/metabolismo , Humanos , Inflamación/metabolismo , Interleucina-6/metabolismo , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , Microscopía Confocal , FN-kappa B/metabolismo , Sepsis/metabolismo
5.
BMC Gastroenterol ; 15: 172, 2015 Dec 08.
Artículo en Inglés | MEDLINE | ID: mdl-26642931

RESUMEN

BACKGROUND: The relationship between nutrition and Crohn's disease (CD) is complex and involves several therapeutic possibilities including: nutrition treatment for malnourished patients, optimization of growth and development, prevention of osteoporosis, first-line therapy for active disease, and maintenance of disease remission. In children and adolescents with CD, malnutrition is a common problem that adversely affects the prognosis. In at-risk adolescent CD patients, it is important to assess body composition, food intake, energy expenditure, nutrient balance and serum levels of nutrients before planning interventions for this population. The aim of this study was to provide a snapshot of the nutritional status of adolescents with CD in Brazil. METHODS: We prospectively selected 22 patients with mildly to moderately active CD, 29 patients with inactive CD and 35 controls (first-degree relatives of and in the same age bracket as the CD patients). The age range of participants was between 13.2 and 19.4 years old. We collected anthropometric data including weight, height, and body mass index (BMI), which were expressed as Z scores: weight-for-age, height-for-age and BMI-for-age, respectively, as well as using bioimpedance to determine body composition and assessing the Tanner stage. We also assessed macronutrients and micronutrients (serum levels and dietary intake of both). We used the chi-square test to determine whether any of the studied variables were associated with inactive or active CD. The level of significance was set at 5 % (p < 0.05). We have written informed parental consent for participation for any minors and written informed consent for any participants that were adults. RESULTS: The mean values for lean body mass, Tanner stage, height-for-age Z score and BMI-for-age Z score were lower in the active CD group than in the inactive CD and control groups (p < 0.05 for both). Compared with the controls, the CD patients showed significant differences in terms of the quality of dietary intake (particularly in caloric intake, dietary protein intake, dietary fiber intake, and micronutrient intake), which were reflected in the serum levels of nutrients, mainly vitamins A and E (p < 0.05). CONCLUSIONS: Adolescents with CD (including those with mildly to moderately active or inactive disease) have a nutritional risk, which makes it important to conduct nutritional assessments in such patients.


Asunto(s)
Fenómenos Fisiológicos Nutricionales de los Adolescentes , Enfermedad de Crohn/complicaciones , Trastornos Nutricionales/etiología , Estado Nutricional , Adolescente , Antropometría , Composición Corporal , Índice de Masa Corporal , Brasil , Distribución de Chi-Cuadrado , Enfermedad de Crohn/sangre , Estudios Transversales , Encuestas sobre Dietas , Ingestión de Alimentos , Ingestión de Energía , Femenino , Humanos , Masculino , Micronutrientes/sangre , Trastornos Nutricionales/sangre , Estudios Prospectivos , Vitamina A/sangre , Vitamina E/sangre , Vitaminas/sangre , Adulto Joven
6.
J Clin Lipidol ; 2024 Apr 23.
Artículo en Inglés | MEDLINE | ID: mdl-38906752

RESUMEN

Cerebrotendinous xanthomatosis (CTX) is a rare inherited metabolic disease attributed to the mutation of the gene CYP27A1, resulting in sterol 27-hydroxylase deficiency characterized by deposition of cholestanol and cholesterol in several tissues, like the central nervous system and tendons. Furthermore, cataracts, gallstones, diarrhea and premature atherosclerosis have been reported. Nonetheless, clinical development is extremely heterogeneous in CTX. We report here two cases of CTX genetic alteration in the absence of cholestanol elevation in plasma and tendons but with prominent xanthomas. We propose that CTX may not be characteized by increased plasma cholestanol concentration due to alteration in the sterol 27-hydroxylase gene, but is a more complex pathology where there is significant genetic heterogeneity caused by various CYP27A1 mutations.

7.
Front Immunol ; 15: 1389551, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38966642

RESUMEN

Introduction: Pathogenesis of cutaneous leishmaniases involves parasite growth, persistent inflammation, and likely participation of lipoproteins (LP). The cholesteryl ester transfer protein (CETP), involved in LP remodeling, has been shown to participate in the inflammatory response and the evolution of infectious conditions. Methods: We evaluated the impact of the presence of CETP on infection by Leishmania (L.) amazonensis in an experimental model of cutaneous leishmaniasis using C57BL6/J mice transgenic for human CETP (CETP), having as control their littermates that do not express the protein, wild-type (WT) mice. The progression of the lesion after infection in the footpad was monitored for 12 weeks. Two groups of animals were formed to collect the plantar pad in the 4th and 12th week post-infection. Results: The lesion increased from the 3rd week onwards, in both groups, with a gradual decrease from the 10th week onwards in the CETP group compared to the WT group, showing a reduction in parasitism and an improvement in the healing process, a reduction in CD68+ cells, and an increase in CD163+ and CD206, characterizing a population of M2 macrophages. A reduction in ARG1+ cells and an increase in INOS+ cells were observed. During infection, the LP profile showed an increase in triglycerides in the VLDL fraction in the CETP group at 12 weeks. Gene expression revealed a decrease in the CD36 receptor in the CETP group at 12 weeks, correlating with healing and parasite reduction. In vitro, macrophages derived from bone marrow cells from CETP mice showed lower parasite load at 48 h and, a reduction in arginase activity at 4 h accompanied by increased NO production at 4 and 24 h compared to WT macrophages, corroborating the in vivo findings. Discussion: The data indicate that the presence of CETP plays an important role in resolving Leishmania (L.) amazonensis infection, reducing parasitism, and modulating the inflammatory response in controlling infection and tissue repair.


Asunto(s)
Proteínas de Transferencia de Ésteres de Colesterol , Leishmaniasis Cutánea , Macrófagos , Ratones Endogámicos C57BL , Ratones Transgénicos , Animales , Proteínas de Transferencia de Ésteres de Colesterol/genética , Proteínas de Transferencia de Ésteres de Colesterol/metabolismo , Leishmaniasis Cutánea/inmunología , Leishmaniasis Cutánea/parasitología , Leishmaniasis Cutánea/metabolismo , Ratones , Macrófagos/inmunología , Macrófagos/metabolismo , Macrófagos/parasitología , Humanos , Progresión de la Enfermedad , Modelos Animales de Enfermedad
8.
Sci Rep ; 13(1): 8998, 2023 06 02.
Artículo en Inglés | MEDLINE | ID: mdl-37268673

RESUMEN

The association between plasma lipids and breast cancer (BC) has been extensively explored although results are still conflicting especially regarding the relationship with high-density lipoprotein cholesterol (HDLc) levels. HDL mediates cholesterol and oxysterol removal from cells limiting sterols necessary for tumor growth, inflammation, and metastasis and this may not be reflected by measuring HDLc. We addressed recently diagnosed, treatment-naïve BC women (n = 163), classified according to molecular types of tumors and clinical stages of the disease, in comparison to control women (CTR; n = 150) regarding plasma lipids and lipoproteins, HDL functionality and composition in lipids, oxysterols, and apo A-I. HDL was isolated by plasma discontinuous density gradient ultracentrifugation. Lipids (total cholesterol, TC; triglycerides, TG; and phospholipids, PL) were determined by enzymatic assays, apo A-I by immunoturbidimetry, and oxysterols (27, 25, and 24-hydroxycholesterol), by gas chromatography coupled with mass spectrometry. HDL-mediated cell cholesterol removal was determined in macrophages previously overloaded with cholesterol and 14C-cholesterol. Lipid profile was similar between CTR and BC groups after adjustment per age. In the BC group, lower concentrations of TC (84%), TG (93%), PL (89%), and 27-hydroxicholesterol (61%) were observed in HDL, although the lipoprotein ability in removing cell cholesterol was similar to HDL from CRT. Triple-negative (TN) BC cases presented higher levels of TC, TG, apoB, and non-HDLc when compared to other molecular types. Impaired HDL functionality was observed in more advanced BC cases (stages III and IV), as cholesterol efflux was around 28% lower as compared to stages I and II. The altered lipid profile in TN cases may contribute to channeling lipids to tumor development in a hystotype with a more aggressive clinical history. Moreover, findings reinforce the dissociation between plasma levels of HDLc and HDL functionality in determining BC outcomes.


Asunto(s)
Oxiesteroles , Neoplasias de la Mama Triple Negativas , Humanos , Femenino , Apolipoproteína A-I , Cromatografía de Gases y Espectrometría de Masas , Lipoproteínas , Colesterol , Triglicéridos , HDL-Colesterol
9.
Clinics (Sao Paulo) ; 78: 100305, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37976650

RESUMEN

INTRODUCTION: Treatments of Inflammatory Bowel Disease (IBD) are able to control symptoms in most cases, however, a fraction of patients do not improve or have a loss of response to treatments, making it important to explore new therapeutic strategies. Hyperbaric oxygen therapy (HBO) may represent one of them. The aim of this study was to evaluate the effects of HBO therapy in an experimental model of IBD. METHODS: Sixty male BALBc mice were divided into six groups. Group 1 was colitis-induced with trinitrobenzene sulfonic acid (TNBS) + ethanol, group 2 received TNBS + ethanol plus HBO, group 3 received only ethanol, group 4 received ethanol plus HBO, group 5 received saline solution, and group 6 received saline solution plus HBO. HBO was performed for four days, subsequently, the mice were evaluated daily. At the end of the study, samples from the intestine were collected for histological analysis as well as for measurement of antioxidant enzymes and cytokine levels. RESULTS: HBO significantly improved the clinical and histological status of the animals. Treatment with HBO increased the activity of the antioxidant enzymes superoxide dismutase (SOD) and glutathione peroxidase (GPx) in all of the groups; moreover, the difference was only significant between the TNBS and TNBS + HBO groups and treatments promoted a reduction in the proinflammatory cytokines IFN-γ, IL-12, IL-17 and TNF-α and increased the anti-inflammatory cytokines IL-4 and IL-10, with no changes in IL-13. CONCLUSION: HBO effectively treats TNBS-induced colitis by increasing the activity of antioxidant enzymes and modulating cytokine profiles.


Asunto(s)
Colitis , Enfermedad de Crohn , Oxigenoterapia Hiperbárica , Enfermedades Inflamatorias del Intestino , Humanos , Masculino , Ratones , Animales , Antioxidantes/farmacología , Enfermedad de Crohn/terapia , Solución Salina/efectos adversos , Estrés Oxidativo , Colitis/inducido químicamente , Colitis/tratamiento farmacológico , Citocinas , Modelos Teóricos , Etanol/efectos adversos
10.
IUBMB Life ; 64(4): 296-306, 2012 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-22378769

RESUMEN

The plasma cholesterol-reducing effect of phytosterols (PS) has been recognized in several studies, but the usefulness of PS in preventing coronary heart disease remains controversial, as some investigations claim that the high PS concentrations found in plasma and specific tissues are related to an increased risk of cardiovascular events. It has also been demonstrated that PS may induce inflammation and reduce cholesterol efflux from macrophages, conditions that are directly implicated in the development of atherosclerosis. As to arterial dysfunction and atherosclerosis, some studies have concluded that plasma PS concentrations are unrelated or only weakly related or that PS intake or plasma PS concentrations are harmful. Thus, in light of the National Cholesterol Education Program-ATPIII report, it is necessary to evaluate the relevance of their findings. To this end, we have evaluated the studies conducted on cells, animal models, and humans regarding the influence of PS on the development of atherosclerosis.


Asunto(s)
Aterosclerosis/prevención & control , Dieta , Fitosteroles/administración & dosificación , Animales , Aterosclerosis/etiología , Aterosclerosis/metabolismo , Colesterol/metabolismo , Colesterol en la Dieta/farmacocinética , Dieta/efectos adversos , Medicina Basada en la Evidencia , Humanos , Absorción Intestinal , Ratones , Modelos Biológicos , Fitosteroles/efectos adversos , Fitosteroles/farmacocinética , Factores de Riesgo , Investigación Biomédica Traslacional
11.
Aging (Albany NY) ; 14(3): 1549-1561, 2022 02 07.
Artículo en Inglés | MEDLINE | ID: mdl-35130181

RESUMEN

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 27- hydroxycholesterol 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.


Asunto(s)
Enfermedad de Alzheimer , Envejecimiento , Enfermedad de Alzheimer/metabolismo , Animales , Apolipoproteínas E/genética , Apolipoproteínas E/metabolismo , Encéfalo/metabolismo , Colesterol/metabolismo , Estudios de Cohortes , Humanos , Hígado/metabolismo , Ratones , Ratas
12.
Clinics (Sao Paulo) ; 77: 100107, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36179527

RESUMEN

BACKGROUND: This study aimed to evaluate the associations between Lipoprotein (a) ‒ Lp(a) levels and carotid Intima-Media Thickness (cIMT) and with carotid plaques in healthy subjects because of previous contradictory data. METHODS: A total of 317 healthy normolipidemic subjects (20‒77 years old) were selected. The cIMT and atherosclerotic plaques were determined by B-mode ultrasonography. Mann-Whitney tests were performed to compare the groups according to Lp(a) levels and to explore the associations between Lp(a), carotid plaques, and cIMT, logistic and linear regression analyses were performed. RESULTS: Studied population (51% females, median age 43 years old) presented carotid plaques and cIMT ≥ 0.9 mm in 23% and 18% of the participants, respectively. The group with Lp(a) levels > 30 mg/dL presented significantly higher age and atherosclerotic plaques. Indeed, multivariate linear regression analysis showed a significant association between Lp(a), age, and race. On the other hand, logistic regression analysis demonstrated that the subjects with Lp(a) > 30 mg/dL have a significantly high risk of carotid plaques. CONCLUSION: The data from the present study indicate that Lp(a) levels above 30 mg/dL contribute to the development of carotid plaques even in apparently healthy participants.


Asunto(s)
Enfermedades de las Arterias Carótidas , Placa Aterosclerótica , Adulto , Anciano , Enfermedades de las Arterias Carótidas/diagnóstico por imagen , Enfermedades de las Arterias Carótidas/epidemiología , Grosor Intima-Media Carotídeo , Femenino , Humanos , Lipoproteína(a) , Masculino , Persona de Mediana Edad , Placa Aterosclerótica/diagnóstico por imagen , Factores de Riesgo , Adulto Joven
13.
Front Nutr ; 9: 723555, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35299760

RESUMEN

Non-cholesterol sterols are transported in plasma lipoproteins and are consequently important in cholesterol metabolism. We investigated the distribution of non-cholesterol sterol precursors of cholesterol synthesis (NCSPCS), oxysterols, and phytosterols in lipoproteins of healthy subjects differing according to HDL-Cholesterol (HDL-C) plasma levels. Elevated NCSPCS (desmosterol, lathosterol) in the High HDL group suggests that HDL exports these sterols from cells, but not the cholesterol metabolite 24-OHC which was higher in the Low HDL group than in the High HDL group. 27-hydroxycholesterol (27OH-C) plasma levels did not differ between groups. Percentage of NCSPCS and phytosterols predominates in LDL, but did not differ between groups. Thirty percent of desmosterol and lathosterol are present in HDL, with the High HDL group carrying higher percentage of these sterols. A high percentage of campesterol and sitosterol in HDL suggests that phytosterols are absorbed by enterocytes, and that HDL could be a marker of the ABCA1/ApoA1 intestinal activity.

14.
Circ Genom Precis Med ; 15(3): e003390, 2022 06.
Artículo en Inglés | MEDLINE | ID: mdl-35549507

RESUMEN

BACKGROUND: Sitosterolemia is a rare autosomal recessive disorder caused by homozygous or compound heterozygous variants in ABCG5/ABCG8. The disease is characterized by increased plasma plant sterols. Small case series suggest that patients with sitosterolemia have wide phenotypic heterogeneity with great variability on either plasma cholesterol levels or development of atherosclerotic cardiovascular disease. The present study aims to characterize the prevalence and clinical features of sitosterolemia participating in a familial hypercholesterolemia genetic cascade screening program. METHODS: From 443 familial hypercholesterolemia index cases, 260 were negative for familial hypercholesterolemia genes and were sequenced for the ABCG5/8 genes. Clinical and laboratory characteristics of affected individuals were determined. RESULTS: Eight (3.1%) index cases were found to be homozygous or compound heterozygous variant for ABCG5/ABCG8 genes, confirming the genetic diagnosis of sitosterolemia. Screening their relatives led to the identification of 6 additional confirmed sitosterolemia cases (3 homozygous and 3 compound heterozygous variant) and 18 carriers (heterozygous). The mean age of identified sitosterolemia cases (n=14) was 37.2±19.8 years, 50% were females, and 78.6% (all adults) presented either clinical or subclinical atherosclerotic cardiovascular disease. As expected, affected individuals presented elevated plasma plant sterol levels (mean ß-Sitosterol and campesterol, respectively, 160.3±107.1 and 32.0±19.6 µg/mL) and the highest plasma LDL (low-density lipoprotein)-cholesterol was 269.0±120.0 mg/dL (range: 122-521 mg/dL). LDL-cholesterol mean reduction with therapy among cases was 65%. Eighty-three percent (83%) of identified sitosterolemia patients presented hematologic abnormalities. CONCLUSIONS: Testing genes associated with sitosterolemia in the molecular routine workflow of a familial hypercholesterolemia cascade screening program allowed the precise diagnosis of sitosterolemia in a substantial number of patients with varying LDL-C levels and high incidence of early atherosclerotic cardiovascular disease and hematologic abnormalities.


Asunto(s)
Transportador de Casetes de Unión a ATP, Subfamilia G, Miembro 5 , Transportador de Casete de Unión a ATP, Subfamilia G, Miembro 8 , Enfermedades Cardiovasculares , Hipercolesterolemia , Hiperlipoproteinemia Tipo II , Enfermedades Intestinales , Errores Innatos del Metabolismo Lipídico , Fitosteroles , Transportador de Casetes de Unión a ATP, Subfamilia G, Miembro 5/genética , Transportador de Casete de Unión a ATP, Subfamilia G, Miembro 8/genética , Adolescente , Adulto , Enfermedades Cardiovasculares/genética , Colesterol , LDL-Colesterol , Femenino , Humanos , Hipercolesterolemia/genética , Hiperlipoproteinemia Tipo II/genética , Enfermedades Intestinales/genética , Errores Innatos del Metabolismo Lipídico/genética , Lipoproteínas/genética , Masculino , Persona de Mediana Edad , Fitosteroles/efectos adversos , Adulto Joven
15.
Clinics (Sao Paulo) ; 77: 100028, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35397367

RESUMEN

OBJECTIVES: 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 ‒ LDL-C ≥ 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.


Asunto(s)
Colesterol , Fitosteroles , HDL-Colesterol , LDL-Colesterol , Estudios Cruzados , Humanos
16.
Clinics (Sao Paulo) ; 77: 100111, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36368184

RESUMEN

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 prognostic 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 admission (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 cholesterol 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.


Asunto(s)
Sepsis Neonatal , Sepsis , Choque Séptico , Humanos , Recién Nacido , Masculino , Colesterol , HDL-Colesterol , Citocinas , Interleucina-6 , Interleucina-8 , Lipoproteínas , Monocitos , Sepsis Neonatal/diagnóstico , Estudios Prospectivos , Triglicéridos , Femenino
17.
PLoS One ; 16(10): e0258058, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34665804

RESUMEN

Primary hyperlipidaemia in Schnauzer is characterized by increased plasma triglycerides (TG) and/or total cholesterol (TC) concentration and is associated with an increased risk of developing pancreatitis, insulin resistance and seizures. In humans, omega-3 fatty acids in addition to a low-fat diet can be used to reduce TG and TC. This study evaluated the therapeutic efficacy of omega-3 fatty acids associated to a diet management with two different fat content in Schnauzer with primary hyperlipidaemia. Eighteen dogs with primary hyperlipidaemia were divided into two groups: group 1, n = 10, 8 females, 2 males, age (mean ± standard deviation) of 7.13 ± 2.70 years and body weight (BW) (mean ± standard deviation) of 7.25 ± 1.22 kg were treated with fish oil (approximately 730 mg/day of omega-3) associated with a low-fat and low-calorie diet (approximately 24g of fat/1000 kcal) for 90 days (T90); and group 2, n = 8 dogs, 6 females, 2 males, with 7.0 ± 1.77 years old and average BW of 8.36 ± 1.51 kg, treated with fish oil (approximately 730 mg/day of omega-3) and maintenance diet with moderate amount of fat (approximately 33g of fat/1000 kcal) for 90 days. Plasma TG and TC concentrations and lipoprotein (LP) profile (VLDL, LDL, HDL) were evaluated before and after treatment. TG and TC serum concentrations, expressed in mg/dL (mean ± standard deviation), before and after treatment in group 1 were: TG = 391.30 ± 487.86 (T0) and 118.7 ± 135.21 (T90); TC = 308.2 ± 63.06 (T0) and 139 ± 36.91 (T90). As for group 2, TG = 391.63 ± 336.89 (T0) and 250.75 ± 211.56 (T90); TC = 257.25 ± 92.88 (T0) and 207.25 ± 63.79 (T90). A reduction (p<0.05) of TG and TC was observed in both groups. The distribution of TG and TC among LP was not different between the pre (T0) and post treatment (T90) periods. After 90 days of treatment, the administration of omega-3 fatty acids, associated with a low-fat or maintenance diet reduced triglyceridemia and cholesterolemia without altering LP profile. The current investigation shows that both therapies were effective in reducing plasma TC and TG concentrations without altering LP profile.


Asunto(s)
Colesterol/sangre , Enfermedades de los Perros/tratamiento farmacológico , Ácidos Grasos Omega-3/administración & dosificación , Lipoproteínas/sangre , Enfermedades Metabólicas , Triglicéridos/sangre , Animales , Perros , Femenino , Masculino , Enfermedades Metabólicas/tratamiento farmacológico , Enfermedades Metabólicas/veterinaria
18.
Front Immunol ; 12: 684076, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34367144

RESUMEN

Cholesterol-ester transfer protein (CETP) plays a role in atherosclerosis, the inflammatory response to endotoxemia and in experimental and human sepsis. Functional alterations in lipoprotein (LP) metabolism and immune cell populations, including macrophages, occur during sepsis and may be related to comorbidities such as chronic obstructive pulmonary disease (COPD). Macrophages are significantly associated with pulmonary emphysema, and depending on the microenvironment, might exhibit an M1 or M2 phenotype. Macrophages derived from the peritoneum and bone marrow reveal CETP that contributes to its plasma concentration. Here, we evaluated the role of CETP in macrophage polarization and elastase-induced pulmonary emphysema (ELA) in human CETP-expressing transgenic (huCETP) (line 5203, C57BL6/J background) male mice and compared it to their wild type littermates. We showed that bone marrow-derived macrophages from huCETP mice reduce polarization toward the M1 phenotype, but with increased IL-10. Compared to WT, huCETP mice exposed to elastase showed worsened lung function with an increased mean linear intercept (Lm), reflecting airspace enlargement resulting from parenchymal destruction with increased expression of arginase-1 and IL-10, which are M2 markers. The cytokine profile revealed increased IL-6 in plasma and TNF, and IL-10 in bronchoalveolar lavage (BAL), corroborating with the lung immunohistochemistry in the huCETP-ELA group compared to WT-ELA. Elastase treatment in the huCETP group increased VLDL-C and reduced HDL-C. Elastase-induced pulmonary emphysema in huCETP mice promotes lung M2-like phenotype with a deleterious effect in experimental COPD, corroborating the in vitro result in which CETP promoted M2 macrophage polarization. Our results suggest that CETP is associated with inflammatory response and influences the role of macrophages in COPD.


Asunto(s)
Proteínas de Transferencia de Ésteres de Colesterol/fisiología , Macrófagos/metabolismo , Enfisema Pulmonar/inmunología , Animales , Arginasa/metabolismo , Líquido del Lavado Bronquioalveolar/citología , Proteínas de Transferencia de Ésteres de Colesterol/deficiencia , Proteínas de Transferencia de Ésteres de Colesterol/genética , Interleucina-10/metabolismo , Recuento de Leucocitos , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , Elastasa Pancreática/efectos adversos , Fenotipo , Enfermedad Pulmonar Obstructiva Crónica/fisiopatología , Enfisema Pulmonar/inducido químicamente , Enfisema Pulmonar/genética
19.
Biosci Rep ; 40(7)2020 07 31.
Artículo en Inglés | MEDLINE | ID: mdl-32579186

RESUMEN

It is controversial whether atherosclerosis is linked to increased intestinal cholesterol absorption or synthesis in humans. The aim of the present study was to relate atherosclerosis to the measurements of plasma markers of cholesterol synthesis (desmosterol, lathosterol) and absorption (campesterol, sitosterol). In healthy male (n=344), non-obese, non-diabetics, belonging to the city of São Paulo branch of the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil), we measured in plasma these non-cholesterol sterol markers, together with their anthropometric, dietary parameters, traditional atherosclerotic risk factors, and blood chemistry, coronary arterial calcium score (CAC), and ultrasonographically measured common carotid artery intima-media thickness (CCA-IMT). Cases with CAC>zero had the following parameters higher than cases with CAC = zero: age, waist circumference (WC), plasma total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-C), and non-high density lipoprotein-cholesterol (non HDL-C). Plasma desmosterol and campesterol, duly corrected for TC, age, body mass index (BMI), waist circumference (WC), hypertension, smoking, and the homeostasis model assessment-insulin resistance (HOMA-IR) correlated with CAC, but not with CCA-IMT. The latter related to increased age, BMI, waist circumference (WC), and systolic blood pressure (SBP). Plasma HDL-C concentrations did not define CAC or CCA-IMT degrees, although in relation to the lower tertile of HDL-C in plasma the higher tertile of HDL-C had lower HOMA-IR and concentration of a cholesterol synthesis marker (desmosterol). Present work indicated that increased cholesterol synthesis and absorption represent primary causes of CAD, but not of the common carotid artery atherosclerosis.


Asunto(s)
Aterosclerosis/diagnóstico , Calcio/análisis , Vasos Coronarios/química , Adulto , Anciano , Aterosclerosis/sangre , Biomarcadores/sangre , Biomarcadores/metabolismo , Índice de Masa Corporal , Brasil , Arteria Carótida Común/diagnóstico por imagen , Grosor Intima-Media Carotídeo , Colesterol/análogos & derivados , Colesterol/sangre , Colesterol/metabolismo , HDL-Colesterol/sangre , LDL-Colesterol/sangre , Vasos Coronarios/diagnóstico por imagen , Estudios Transversales , Desmosterol/sangre , Desmosterol/metabolismo , Femenino , Humanos , Absorción Intestinal , Mucosa Intestinal/metabolismo , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Fitosteroles/sangre , Fitosteroles/metabolismo , Estudios Prospectivos , Sitoesteroles/sangre , Sitoesteroles/metabolismo , Tomografía Computarizada por Rayos X , Ultrasonografía
20.
J Vet Diagn Invest ; 21(2): 203-7, 2009 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-19286498

RESUMEN

Obesity and endogenous hyperadrenocorticism (HAC) are common clinical conditions in veterinary practice, and both conditions have clinical and laboratory similarities, such as weight gain and dyslipidemia. The objective of the present study was to characterize and compare the lipid profiles and plasma lipoprotein fractions in healthy dogs (n = 10), in obese dogs (n = 10), and in dogs with HAC (n = 6). All of the dogs were client owned. The lipoproteins were separated by fast protein liquid chromatography, and the plasma concentrations of total cholesterol and total triacylglycerol (TAG) were determined by enzymatic methods. When compared with the healthy and obese groups, dogs with HAC had a significant increase (P < 0.01) in the total concentrations of TAGs and cholesterol (CHOL), with higher distribution in the very low-density lipoprotein (VLDL)-CHOL fractions. In addition, the distributions of the high-density lipoprotein (HDL)-CHOL and HDL-TAG fractions were significantly lower (P < 0.01) in dogs with HAC than in healthy dogs. Considering the animals in this study, it was determined that the dogs with HAC differed significantly from the healthy and obese dogs regarding the metabolism of CHOL and TAG, as well as their VLDL and HDL fractions. Similar laboratory findings could allow veterinarians to distinguish obese dogs from those with HAC. In addition, dogs with HAC may be at higher risk for developing metabolic and atherosclerotic complications.


Asunto(s)
Hiperfunción de las Glándulas Suprarrenales/veterinaria , Enfermedades de los Perros/sangre , Perros/sangre , Lípidos/sangre , Obesidad/veterinaria , Hiperfunción de las Glándulas Suprarrenales/sangre , Animales , Colesterol/sangre , Cromatografía/veterinaria , Femenino , Masculino , Obesidad/sangre , Triglicéridos/sangre
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