RESUMO
Dyslipidemia is described as a hallmark of metabolic syndrome, promoting a stage of metabolic inflammation (metainflammation) that could lead to misbalances in energetic metabolism, contributing to insulin resistance, and modifying intracellular cholesterol pathways and the renin-angiotensin system (RAS) in pancreatic islets. Low-density lipoprotein (LDL) hypercholesterolemia could disrupt the tissue communication between Langerhans ß-cells and hepatocytes, wherein extracellular vesicles (EVs) are secreted by ß-cells, and exposition to LDL can impair these phenomena. ß-cells activate compensatory mechanisms to maintain insulin and metabolic homeostasis; therefore, the work aimed to characterize the impact of LDL on ß-cell cholesterol metabolism and the implication on insulin secretion, connected with the regulation of cellular communication mediated by EVs on hepatocytes. Our results suggest that ß-cells can endocytose LDL, promoting an increase in de novo cholesterol synthesis targets. Notably, LDL treatment increased mRNA levels and insulin secretion; this hyperinsulinism condition was associated with the transcription factor PDX-1. However, a compensatory response that maintains basal levels of intracellular calcium was described, mediated by the overexpression of calcium targets PMCA1/4, SERCA2, and NCX1, together with the upregulation of the unfolded protein response (UPR) through the activation of IRE1 and PERK arms to maintain protein homeostasis. The LDL treatment induced metainflammation by IL-6, NF-κB, and COX-2 overexpression. Furthermore, LDL endocytosis triggered an imbalance of the RAS components. LDL treatment increased the intracellular levels of cholesterol on lipid droplets; the adaptive ß-cell response was portrayed by the overexpression of cholesterol transporters ABCA1 and ABCG1. Therefore, lipotoxicity and hyperinsulinism induced by LDL were regulated by the natural compound auraptene, a geranyloxyn coumarin modulator of cholesterol-esterification by ACAT1 enzyme inhibition. EVs isolated from ß-cells impaired insulin signaling via mTOR/p70S6Kα in hepatocytes, a phenomenon regulated by auraptene. Our results show that LDL overload plays a novel role in hyperinsulinism, mechanisms associated with a dysregulation of intracellular cholesterol, lipotoxicity, and the adaptive UPR, which may be regulated by coumarin-auraptene; these conditions explain the affectations that occur during the initial stages of insulin resistance.
RESUMO
La proteína C-reactiva ultrasensible (PCR-us) es un marcador de riesgo cardiovascular. En niños mexicanos sanos hay escasa evidencia que asocie los niveles séricos de este marcador con la dieta. El objetivo fue asociar los niveles séricos de PCR-us con la composición de la dieta en niños escolares mexicanos. El estudio fue transversal e incluyó 300 niños aparentemente sanos de 10 a12 años de edad. La cuantificación de PCR-us se realizó mediante nefelometría. La dieta se cuantificó con un cuestionario validado de frecuencia de consumo alimentos. Mediante el paquete estadístico SPSS v18, se realizaron pruebas de estadística descriptiva, correlación y modelos de regresión multivariada. El 53,7% fueron niñas y el 46,3% niños. La mediana de la PCR-us fue de 0,3 mg/L (rango: 0,3-6,8 mg/L). Se observó una correlación directa significativa entre la concentración sérica de la PCR-us con la ingesta de proteínas (rho= 0,126, p= 0,029), ácidos grasos totales (rho= 0,128, p= 0,027), ácidos grasos saturados (rho= 0,159, p= 0,006). Mediante el análisis de regresión múltiple se asoció la PCR-us con la ingesta de proteínas (β= 0,203, p=0,037) e inversamente con los granos enteros (β=-0,175, p= 0,002). Con el resto de las variables no se observó asociación significativa. La concentración sérica de la PCR-us se asoció directamente con el consumo de proteínas, ácidos grasos totales y saturados e indirectamente con el consumo de granos enteros.
The high-Sensitivity C-Reactive Protein (hs-CRP) is a cardiovascular risk marker. In healthy Mexican children, there islittle evidence that shows any relationship between serum levels of this marker with diet. The objective of this studywas to associate serum levels of hs-CRP with the diet composition in Mexican school children. The cross-sectional study included 300 seemingly healthy children of 10 to 12 years of age, 53.7% were girls and 46.3% boys.hs-CRP quantification was determined by nephelometry. The diet was quantified with a validated food frequency questionnaire. A descriptive statistical analysis, correlation and multivariate regression models were performed by using the SPSS v18 statistical software. The median of the hs-CRP was 0.3 mg / L (range: 0.3 to 6.8 mg / L). A significant direct correlation was found between serum hs-CRP with protein intake (rho=0.126, p=0.029), total fatty acids (rho = 0.128, p = 0.027) and saturated fatty acids (rho = 0.159, p = 0.006). hs-CRP was associated with the intake of protein (β = 0.203, p = 0.037) by multiple regression analysis, and inversely with whole grains (β = -0.175, p = 0,002). No significant association was found with the rest of the other variables. The serum concentration of hs-CRP was directly associated with the consumption of protein, total and saturated fatty acids and was indirectly proportional with the consumption of whole grains.
Assuntos
Criança , Feminino , Humanos , Masculino , Proteína C-Reativa/análise , Dieta , Alimentos , Estudos Transversais , Estudos Prospectivos , MéxicoRESUMO
The high-Sensitivity C-Reactive Protein (hs-CRP) is a cardiovascular risk marker. In healthy Mexican children, there islittle evidence that shows any relationship between serum levels of this marker with diet. The objective of this studywas to associate serum levels of hs-CRP with the diet composition in Mexican school children. The cross-sectional study included 300 seemingly healthy children of 10 to 12 years of age, 53.7% were girls and 46.3% boys.hs-CRP quantification was determined by nephelometry. The diet was quantified with a validated food frequency questionnaire. A descriptive statistical analysis, correlation and multivariate regression models were performed by using the SPSS v18 statistical software. The median of the hs-CRP was 0.3 mg / L (range: 0.3 to 6.8 mg / L). A significant direct correlation was found between serum hs-CRP with protein intake (rho=0.126, p=0.029), total fatty acids (rho = 0.128, p = 0.027) and saturated fatty acids (rho = 0.159, p = 0.006). hs-CRP was associated with the intake of protein (ß = 0.203, p = 0.037) by multiple regression analysis, and inversely with whole grains (ß = -0.175, p = 0,002). No significant association was found with the rest of the other variables. The serum concentration of hs-CRP was directly associated with the consumption of protein, total and saturated fatty acids and was indirectly proportional with the consumption of whole grains.
Assuntos
Proteína C-Reativa/análise , Dieta , Alimentos , Criança , Estudos Transversais , Feminino , Humanos , Masculino , México , Estudos ProspectivosRESUMO
BACKGROUND: C-reactive protein (CRP) is a nonspecific marker of inflammation with low serum levels, which are not usually detectable. In order to assess cardiovascular risk in adults apparently healthy, ultrasensitive methods are used, and the CRP measured through these techniques is known as ultrasensitive C-reactive protein (US-CRP). Some researchers report an association of US-CRP with some anthropometric parameters in children with no apparent disease. The aim was to associate US-CRP with nutritional status and biochemical profiles in Mexican schoolchildren. METHODS: In this cross-sectional study 300 healthy children (aged 10 to 12 years) were evaluated. Weight, height, body mass index (BMI), waist circumference, body fat percentage, glucose, lipid profiles and US-CRP were measured. Exclusion criteria was: US-CRP > 10mg/L. We used multivariate regression models. RESULTS: 53.7 % were girls and 46.3 % were boys. The US-CRP median was of 0.3 mg/L (range: 0.3 mg/L-6.8 mg/L), and it was positively and significantly correlated with BMI (ß = 0.226, p = 0.032) and LDL-C (ß = -0.267, p = 0.007) and negatively associated with cholesterol (ß = -0.267, p = 0.007). CONCLUSIONS: There is an association between US-CRP and cardiovascular risk indicators, such as obesity and some lipid disorder in childhood; therefore, US-CRP may be used for close examination in Mexican children.
Introducción: la proteína C-reactiva (PCR) es un marcador no específico de inflamación con séricos bajos, los cuales normalmente no son detectables. A fin de evaluar el riesgo cardiovascular en adultos que en apariencia son sanos, se emplean métodos ultrasensibles y la PCR medida con estas técnicas se conoce como proteína C-reactiva ultrasensible (PCR-us). Algunos investigadores reportan una asociación de la PCR-us con algún parámetro antropométrico o bioquímico en niños sin enfermedad aparente. El objetivo de este artículo consistió en asociar la PCR-us con el estado nutricional y el perfil bioquímico en escolares mexicanos. Métodos: estudio transversal en 300 niños sanos de 10 a 12 años de edad. Se midieron peso, talla, índice de masa corporal (IMC), cintura y grasa corporal, glucosa, perfil de lípidos y PCR-us. El criterio de exclusión fue una PCR-us > 10 mg/L. Se utilizaron modelos de regresión multivariada. Resultados: el 53.7 % fueron niñas y el 46.3 % niños. La mediana de la PCR-us fue de 0.3mg/L (rango: 0.3mg/L-6.8mg/L), se relacionó positiva y significativamente con un IMC (ß = 0.226 p = 0.032), LDL-C (ß = 0.203 p = 0.037) y negativamente con colesterol total (CT) (ß = 0.267 p = 0.007); con el resto de las variables la asociación no fue significativa. Conclusión: se puede inferir que existe asociación entre la PCR-us e indicadores de riesgo cardiovascular, como la obesidad y alguna dislipidemia en escolares, por lo que la PCR-us puede ser utilizada para escrutinio en niños mexicanos.