Trastornos asociados y factores de riesgo aterogénicos en escolares y adolescentes obesos / Associated disorders and atherogenic risk factors in obese school children and adolescents

Introducción: la obesidad en la edad pediátrica predispone a la enfermedad aterosclerótica precoz en la adultez, independientemente del peso futuro. Objetivo: caracterizar el patrón antropométrico, morbilidad asociada y factores de riesgo aterogénico en obesos. Métodos: se realizó un estudio descriptivo y prospectivo con 62 pacientes obesos atendidos en la consulta de Endocrinología del Hospital Pediátrico William Soler , entre enero y diciembre de 2016. Fueron analizadas variables demográficas, antropométricas y de riesgo aterogénico por medio de prevalencia (por ciento) y pruebas de hipótesis (significativo: p< 0,05 o coeficiente Eta 1). Resultados: la obesidad fue significativa en escolares y el sexo masculino (p= 0,000). La obesidad abdominal (n= 48/77,4 por ciento) predominó en el sexo femenino (n= 20/90,9 por ciento), y entre los 6 y 10 años (n= 14/63,6 por ciento). La obesidad generalizada tuvo diagnóstico significativamente superior que la obesidad abdominal (p= 0,001) y fue independiente del sexo (Eta= 0,049) y la edad (p= 0,066). La prevalencia de acantosis nigricans (n= 39/62,9 por ciento) fue significativa (p= 0,042). Las alteraciones humorales, clínicas y ecográficas analizadas se manifestaron por encima de 70 por ciento en presencia de obesidad abdominal y la generalizada, ambas asociadas con elevación de proteína C reactiva (p< 0,05), y a su vez, la generalizada con remodelación ventricular izquierda (p= 0,049). Conclusión: la obesidad es distintiva de los escolares y del sexo masculino, pero la de tipo abdominal caracteriza a las niñas; existe una baja prevalencia de factores de riesgo aterogénico en los pacientes estudiados. La adiposidad abdominal y la generalizada implican un incremento de la proteína C reactiva plasmática; se evidencia el remodelado ventricular izquierdo cuando existe obesidad generalizada(AU)

Introduction: obesity in the pediatric age predisposes to early atherosclerotic disease in adulthood, regardless of future weight. Objective: to characterize the anthropometric pattern, associated morbidity and atherogenic risk factors in obese patients. Methods: a descriptive and prospective study was carried out with 62 obese patients attended in the Endocrinology clinic of William Soler Pediatric Hospital, from January to December 2016. Demographic, anthropometric and atherogenic risk variables were analyzed by means of prevalence (percent) and hypothesis testing (significant: p< 0.05 or Eta coefficient 1). Results: obesity was significant in schoolchildren and male sex (p= 0.000). Abdominal obesity (n= 48/77.4 percent) predominated in females (n= 20/90.9 percent), and among 6 and 10 years old (n= 14/63.6 percent). Generalized obesity had a significantly higher diagnosis than abdominal obesity (p = 0.001) and didn´t have relation with sex (Eta= 0.049) and age (p= 0.066). The prevalence of acanthosis nigricans (n= 39 / 62.9 percent) was significant (p= 0.042). The humoral, clinical and ultrasonographic alterations analyzed were above 70 percent in the presence of abdominal and generalized obesity, both associated with elevated C-reactive protein (p< 0.05), and at the same time, the generalized with left ventricular remodeling (p= 0.049). Conclusions: obesity is distinctive among school children and males, but abdominal type characterizes girls. There is a low prevalence of atherogenic risk factors in the patients studied. Abdominal and generalized adiposity imply an increase in plasma C-reactive protein. Left ventricular remodeling is evidenced when there is generalized obesity(AU)

Effect of classic ketogenic diet treatment on lipoprotein subfractions in children and adolescents with refractory epilepsy.

OBJECTIVE: The aim of this study was to evaluate the effects of the classic ketogenic diet (KD) on low-density lipoprotein (LDL) and high-density lipoprotein (HDL) subfractions in children and adolescents with refractory epilepsy. METHODS: This prospective study recruited children and adolescents of either sex, whose epilepsy was refractory to treatment with multiple drugs. To be included, the patient had to have an indication for treatment with the KD and be treated as an outpatient. At baseline and after 3 and 6 mo of the KD, lipid profile (total cholesterol [TC], triacylglycerols [TG], LDL cholesterol [LDL-C], and HDL cholesterol [HDL-C]), apolipoproteins (apoA-I and apoB), 10 subfractions of HDL, 7 subfractions of LDL, LDL phenotype, and LDL size were analyzed using the Lipoprint system. RESULTS: The lipid profile components (TC, TG, LDL-C, HDL-C, apoA-I, and apoB) increased during the 3-mo follow-up, and remained consistent after 6 mo of treatment. Similarly, non-HDL-C, TC/HDL-C, LDL-C/HDL-C, and apoB/apoA-I ratios, representing atherogenic particles, significantly increased. In contrast, qualitative lipoprotein characteristics progressively changed during the follow-up period. Small LDL subfractions increased, and this profile was related with reduced LDL size (27.3 nm to 26.7 nm). The LDL phenotype became worse; 52.1% of the patients had a non-A phenotype after 6 mo of the KD. Small HDL subfractions decreased only after 6 mo of the KD. CONCLUSIONS: KD treatment promotes negative changes in lipoprotein size and phenotype, contributing to atherogenic risk in these patients.

Dislipidemia aterogénica en latino américa: prevalencia, causas y tratamiento / Atherogenic dyslipidemia in Latin America: prevalence, causes and treatment

En las guías clínicas actuales, la dislipidemia aterogénica (DA) es una entidad no muy atendida. Debido a las frecuentes alteraciones en los lípidos asociados a la DA en Latino América (LA). Métodos: organizamos un grupo de expertos denominado Academia Latino Americana para el estudio de los Lípidos (ALALIP) para así generar un documento con análisis de su prevalencia y recomendaciones terapéuticas prácticas. Se utilizó la metodología Delphi modificada, con una revisión integral de la literatura y énfasis en las publicaciones con implicaciones para LA. Subsecuentemente, desarrollamos preguntas claves para ser discutidas. Resultados: En Latinoamérica (LA) no existe un estudio global sobre los factores de riesgo que representan a la totalidad de la población. El análisis sistemático de las encuestas nacionales de salud y de los estudios sistemáticos de cohorte muestran consistentemente una alta prevalencia de las anormalidades lipídicas que definen la DA. La concentración baja del colesterol unido a las lipoproteínas de alta densidad (C-HDL) varía entre 34,1% a 53,3% y la de triglicéridos (TG) elevados del 25,5% al 31,2%, con mayor prevalencia entre los hombres. La DA bien puede ser tratada con los cambios del estilo de vida (CTEV) como ncremento en laactividad física, dieta baja en carbohidratos y alta en ácidos grasos poliinsaturados, tales como los ácidos grasos omega-3 como intervención primaria. De ser necesario, esta estrategia sera suplementada con terapia farmacológica como la monoterapia con estatinas o la combinación de fibratos/ácidos grasos omega-3. Conclusiones: Las anormalidades lipídicas que definen la DA tienen una elevada prevalencia en LA; su interacción con un estilo de vida no saludable, herencia y cambios epigenéticos están ligados a sus posibles causas. La DA es una causa importante de riesgo cardiovascular residual (RCVR) que debe ser diagnosticada y tratada. Es importante y necesario diseñar un estudio global de factores de riesgo en LA para conocer la real prevalencia de la DA(AU)

In the current clinical guidelines, atherogenic Med Interna (Caracas) 2017; 33 (3): 121 - 139 Dislipidemia Aterogénica en Latino América: Prevalencia, causas y tratamiento Carlos I. Ponte-N, Jesús E. Isea-Pérez, Alberto J. Lorenzatti, Patricio López-Jaramillo, Fernando Stuardo Wyss-Q, Xavier Pintó, Fernando Lanas, Josefina Medina, Livia T. Machado-H, Mónica Acevedo, Paola Varleta Alfonso Bryce, Carlos Carrera, Carlos Ernesto Peñaherrera, José Ramón Gómez-M, Alfredo Lozada, Alonso Merchan-V, Daniel Piskorz, Enrique Morales, María Paniagua, Félix Medina-Palomino, Raúl Alejandro Villar-M, Leonardo Cobos, Enrique Gómez-Álvares, Rodrigo Alonso, Juan Colan, Julio Chirinos, Jofre Lara, Vladimir Ullauri, Ildefonso Arocha Documento de la posición de expertos de la Academia Latino Americana para el estudio de los Lípidos (ALALIP) y avalado por la Sociedad Interamericana de Cardiología (SIAC), Sociedad Sur Americana de Cardiología (SSC), el Colegio Panamericano de Endotelio (CPAE) y la Sociedad Internacional de Aterosclerosis (IAS). Publicado en conjunto con las Revistas de la Sociedad Venezolana de Medicina Interna y de la Sociedad Venezolana de ndocrinología y Metabolismo. dyslipidemia (AD) is a poorly recognized entity. Due to the frequent lipid alterations associated with AD in Latin America (LA), we organized a group of experts named Latin American Academy for the study of Lipids (ALALIP), to generate a document to analize it´s prevalence and to offer practical recommendations. Methodology: Using the Delphi methodology, we conducted a comprehensive literature review, with emphasis on those publications with implications for LA. Subsequently we developed key questions to be discussed. Results: In LA There is no a global study on risk factors that represent the entire population. The systematic analysis of national health surveys and regional cohort studies showed a consistent high prevalence of the lipid abnormalities that define AD. Low high density lipoprotein cholesterol (HDL-C) ranges from 34.1% to 53.3% and elevated triglycerides (TG) from 25.5% to 31.2% more prevalent in men. There are multiple causes: high consumption of foods with a high caloric density, cholesterol and trans fats, sedentary lifestyle and epigenetic changes. AD must be well treated with therapeutic changes in lifestyle with increase in physical activities, regular exercise and a diet with a low proportion of carbohydrates and rich in poliunsatured fatty acid, such as omega-3 fatty acids as primary intervention. If needed, this strategy must be supplemented with pharmacological therapies such as monotherapy with statins or a combination of fibrates plus omega-3. fatty acid. conclusions: Lipid abnormalities that define AD have a high prevalence in LA; the interaction between non-healthy lifestyle, inheritance and epigenetic changes, possibly are the cause. AD is an important cause of cardiovascular residual risk (CVRR), that must be diagnosed and treated It is important and necesary to design a global study of risk factors in LA to know the true prevalence of AD(AU)

Novel role of TLR4 in NAFLD development: Modulation of metabolic enzymes expression.

The rise in the prevalence of obesity and metabolic syndrome turned NAFLD as the most common cause of chronic liver diseases worldwide. Although the role of toll like receptors, especially TLR4, as activators of inflammatory pathways in liver diseases is well established, our goal was to investigate if TLR4 activation could modulate metabolic lipid pathways and alter the onset of NAFLD. We used LDL receptor-deficient mice (LDLrKO) fed with an atherogenic diet as a model. The role of TLR4 activation was evaluated by crossing LDLrKO mice with the TLR4 knockout mice. Animals were fed for 12weeks with high-fat high-cholesterol diet (HFD) containing 18% saturated fat and 1.25% cholesterol. TLR4/LDLr KO mice presented lower triacylglyceride (TAG) plasma levels when compared to LDLrKO, despite the type of diet ingested. HFD induced TAG and cholesterol accumulation in the liver of all mice genotypes studied, but TLR4/LDLr KO presented lower TAG accumulation than LDLrKO mice. Gene expression of TAG synthesis enzymes (ApoB100, MTTP, GPAT1 and GPAT4) was not differentially altered in TLR4/LDLr KO and LDLrKO mice. On the other hand, TLR4 deficiency enhanced the expression of several enzymes involved in the oxidation of fatty acids, as follows: ACOX, CPT-1, MTPa, MTBb, PBE and 3-ketoacyl-CoA thiolase. Acyl-carnitine plasma profile showed an increase in C0 and C2 concentration in TLR4/LDLr KO group, corroborating the hypothesis of increased fat oxidation. Our results indicate that TLR4 may have an important role in the onset of steatosis, once its depletion enhances fatty acid oxidation in the liver of mice, preventing triglyceride accumulation.

Atheroprotective remodelling of vascular dermatan sulphate proteoglycans in response to hypercholesterolaemia in a rat model.

Proteoglycan accumulation within the arterial intima has been implicated in atherosclerosis progression in humans. Nevertheless, hypercholesterolaemia is unable to induce intimal thickening and atheroma plaque development in rats. The study was performed to analyse proteoglycans modifications in rats fed with a high-cholesterol diet to understand whether vascular wall remodelling protects against lesions. Sections obtained from rat aortas showed normal features, in intimal-to-media ratio and lipid accumulation. However, focal endothelial hyperplasia and neo-intima rearrangement were observed in high-cholesterol animals. Besides, hypercholesterolaemia induced an inflammatory microenviroment. We determined the expression of different proteoglycans from aortic cells by Western blot and observed a diminished production of decorin and biglycan in high-cholesterol animals compared with control (P < 0.01 and P < 0.05, respectively). Versican was increased in high-cholesterol animals (P < 0.05), whereas perlecan production showed no differences. No modification of the total content of glycosaminoglycans (GAGs) was found between the two experimental groups. In contrast, the chondroitin sulphate/dermatan sulphate ratio was increased in the high-cholesterol group as compared to the control (0.56 and 0.34, respectively). Structural alterations in the disaccharide composition of galactosaminoglycans were also detected by HPLC, as the ratio of 6-sulphate to 4-sulphate disaccharides was increased in high-cholesterol animals (P < 0.05). Our results suggest that attenuation of decorin and biglycan expression might be an effective strategy to inhibit the first step in atherogenesis, although specific GAG structural modification associated with the development of vascular disease took place. Results emphasize the potential application of therapies based on vascular matrix remodelling to treat atherosclerosis.

Anti-atherogenic effects of a new thienylacylhydrazone derivative, LASSBio-788, in rats fed a hypercholesterolemic diet.

The compound LASSBio-788 (N-Allyl (2-thienylidene) 3,4-methylenedioxybenzoylhydrazine) is a thienylacylhydrazone derivative shown to have antiplatelet, vasodilatory, and anti-inflammatory properties in vitro. We hypothesize that LASSBio-788 may exert beneficial effects on atherosclerosis. Male wistar rats were divided into 4 groups: Control group received standard rat chow, hypercholesterolemic group (HC) and HC+788 (compound LASSBio-788 group) received hypercholesterolemic diet for 45 days. HC+788 group received compound LASSBio-788 (100 µmol/kg) once daily in the last 15 days. LASSBio-788 reduced the levels of total cholesterol (109.1 ± 4.3 vs. 361.0 ± 12.8 mg/dl), triglycerides (66.1 ± 1.1 vs. 186.9 ± 17.7 mg/dl), LDLc (63.2 ± 6.1 vs. 330.9 ± 9.7 mg/dl), VLDLc (9.8 ± 1.1 vs. 45.0 ± 4.6 mg/dl) and malondialdehyde (4.8 ± 0.3 vs. 9.4 ± 0.5 nmol/ml) compared to the HC group. LASSBio-788 presented antiplatelet properties and decreased inflammatory markers levels. LASSBio-788 promoted a decrease in contractile response to phenylephrine and an improvement in endothelium-dependent vasorelaxant response by increasing two-fold the expression of nitric oxide synthase (eNOS). Our results suggest that the compound LASSBio-788 represents a new multi-targeted drug candidate for the treatment of atherosclerosis.

Paradoxical effect of a pequi oil-rich diet on the development of atherosclerosis: balance between antioxidant and hyperlipidemic properties

Pequi is the fruit of Caryocar brasiliense and its oil has a high concentration of monounsaturated and saturated fatty acids, which are anti- and pro-atherogenic agents, respectively, and of carotenoids, which give it antioxidant properties. Our objective was to study the effect of the intake of a cholesterol-rich diet supplemented with pequi oil, compared to the same diet containing soybean oil, on atherosclerosis development, and oxidative stress in atherosclerosis-susceptible LDL receptor-deficient mice (LDLr-/-, C57BL/6-background). Female mice were fed a cholesterol-rich diet containing 7% soybean oil (Soybean group, N = 12) or 7% pequi oil (Pequi group, N = 12) for 6 weeks. The Pequi group presented a more atherogenic lipid profile and more advanced atherosclerotic lesions in the aortic root compared to the Soybean group. However, the Pequi group presented a less advanced lesion in the aorta than the Soybean group and showed lower lipid peroxidation (Soybean group: 50.2 ± 7.1; Pequi group: 30.0 ± 4.8 µmol MDA/mg protein) and anti-oxidized LDL autoantibodies (Soybean group: 35.7 ± 9.4; Pequi group: 15.6 ± 3.7 arbitrary units). Peritoneal macrophages from the Pequi group stimulated with zymosan showed a reduction in the release of reactive oxygen species compared to the Soybean group. Our data suggest that a pequi oil-rich diet slows atherogenesis in the initial stages, possibly due to its antioxidant activity. However, the increase of serum cholesterol induces a more prominent LDL migration toward the intimae of arteries, increasing the advanced atherosclerotic plaque. In conclusion, pequi oil associated with an atherogenic diet worsens the lipid profile and accelerates the formation of advanced atherosclerotic lesions despite its antioxidant action.

Paradoxical effect of a pequi oil-rich diet on the development of atherosclerosis: balance between antioxidant and hyperlipidemic properties.

Pequi is the fruit of Caryocar brasiliense and its oil has a high concentration of monounsaturated and saturated fatty acids, which are anti- and pro-atherogenic agents, respectively, and of carotenoids, which give it antioxidant properties. Our objective was to study the effect of the intake of a cholesterol-rich diet supplemented with pequi oil, compared to the same diet containing soybean oil, on atherosclerosis development, and oxidative stress in atherosclerosis-susceptible LDL receptor-deficient mice (LDLr(-/-), C57BL/6-background). Female mice were fed a cholesterol-rich diet containing 7% soybean oil (Soybean group, N = 12) or 7% pequi oil (Pequi group, N = 12) for 6 weeks. The Pequi group presented a more atherogenic lipid profile and more advanced atherosclerotic lesions in the aortic root compared to the Soybean group. However, the Pequi group presented a less advanced lesion in the aorta than the Soybean group and showed lower lipid peroxidation (Soybean group: 50.2 ± 7.1; Pequi group: 30.0 ± 4.8 µmol MDA/mg protein) and anti-oxidized LDL autoantibodies (Soybean group: 35.7 ± 9.4; Pequi group: 15.6 ± 3.7 arbitrary units). Peritoneal macrophages from the Pequi group stimulated with zymosan showed a reduction in the release of reactive oxygen species compared to the Soybean group. Our data suggest that a pequi oil-rich diet slows atherogenesis in the initial stages, possibly due to its antioxidant activity. However, the increase of serum cholesterol induces a more prominent LDL migration toward the intimae of arteries, increasing the advanced atherosclerotic plaque. In conclusion, pequi oil associated with an atherogenic diet worsens the lipid profile and accelerates the formation of advanced atherosclerotic lesions despite its antioxidant action.

Effects of linseed consumption for a short period of time on lipid profile and atherosclerotic lesions in rabbits fed a hypercholesterolaemic diet.

Linseed contains biologically active substances, such as lignans, fibres and linoleic acid, which are believed to provide cardioprotective effects. The objective of the present study was to assess the potential hypolipaemic, anti-atherogenic and anti-inflammatory effects of linseed consumption using an experimental animal model, with rabbits fed a hypercholesterolaemic diet (1 % cholesterol extracted from lyophilised egg). A total of twenty white male rabbits were selected and divided into two groups: group I (GI), control group, ten rabbits; group II (GII), ten rabbits. The animals were fed a hypercholesterolaemic diet for 56 d. For the GII diet, ground linseed was added from day 29 through to day 56. Animals underwent aortic arch and descending aorta dissection on day 56 for histological, morphometric and immunohistochemical analysis. At the end of the experiment, GII animals presented with lower levels of total cholesterol (TC, 10 068·3 v. 16 767·0 mg/l; P < 0·05) and lower levels of LDL-cholesterol (LDL-C; 10 743·2 v. 15 961·2 mg/l; P < 0·05) when compared with the GI control group. There was no significant difference in serum HDL-cholesterol and TAG between the two groups. Almost all animals exhibited type III atherosclerotic lesions in the descending aorta. There was no statistically significant difference between the intima area and the intima:media layer area ratio in both groups. There was no difference between the positive areas for vascular cell adhesion molecule-1 and intercellular adhesion molecule-1 molecules between the groups. Linseed consumption showed hypolipaemic action by reducing LDL-C and TC levels; however, this cholesterol-lowering effect did not reduce the atherosclerotic lesions induced by a hypercholesterolaemic diet (1 % cholesterol) for a short period of time.

A palatable hyperlipidic diet causes obesity and affects brain glucose metabolism in rats.

BACKGROUND: We have previously shown that either the continuous intake of a palatable hyperlipidic diet (H) or the alternation of chow (C) and an H diet (CH regimen) induced obesity in rats. Here, we investigated whether the time of the start and duration of these feeding regimens are relevant and whether they affect brain glucose metabolism. METHODS: Male Wistar rats received C, H, or CH diets during various periods of their life spans: days 30-60, days 30-90, or days 60-90. Experiments were performed the 60th or the 90th day of life. Rats were killed by decapitation. The glucose, insulin, leptin plasma concentration, and lipid content of the carcasses were determined. The brain was sliced and incubated with or without insulin for the analysis of glucose uptake, oxidation, and the conversion of [1-14C]-glucose to lipids. RESULTS: The relative carcass lipid content increased in all of the H and CH groups, and the H30-60 and H30-90 groups had the highest levels. Groups H30-60, H30-90, CH30-60, and CH30-90 exhibited a higher serum glucose level. Serum leptin increased in all H groups and in the CH60-90 and CH30-90 groups. Serum insulin was elevated in the H30-60, H60-90, CH60-90, CH30-90 groups. Basal brain glucose consumption and hypothalamic insulin receptor density were lower only in the CH30-60 group. The rate of brain lipogenesis was increased in the H30-90 and CH30-90 groups. CONCLUSION: These findings indicate that both H and CH diet regimens increased body adiposity independent treatment and the age at which treatment was started, whereas these diets caused hyperglycemia and affected brain metabolism when started at an early age.