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Introduction: The circadian system synchronizes behavior and physiology to the 24-h light- dark (LD) cycle. Timing of food intake and fasting periods provide strong signals for peripheral circadian clocks regulating nutrient assimilation, glucose, and lipid metabolism. Mice under 12 h light:12 h dark (LD) cycles exhibit behavioral activity and feeding during the dark period, while fasting occurs at rest during light. Disruption of energy metabolism, leading to an increase in body mass, was reported in experimental models of circadian desynchronization. In this work, the effects of chronic advances of the LD cycles (chronic jet-lag protocol, CJL) were studied on the daily homeostasis of energy metabolism and weight gain. Methods: Male C57 mice were subjected to a CJL or LD schedule, measuring IPGTT, insulinemia, microbiome composition and lipidemia. Results: Mice under CJL show behavioral desynchronization and feeding activity distributed similarly at the light and dark hours and, although feeding a similar daily amount of food as compared to controls, show an increase in weight gain. In addition, ad libitum glycemia rhythm was abolished in CJL-subjected mice, showing similar blood glucose values at light and dark. CJL also generated glucose intolerance at dark in an intraperitoneal glucose tolerance test (IPGTT), with increased insulin release at both light and dark periods. Low-density lipoprotein (LDL) cholesterolemia was increased under this condition, but no changes in HDL cholesterolemia were observed. Firmicutes/Bacteroidetes ratio was analyzed as a marker of circadian disruption of microbiota composition, showing opposite phases at the light and dark when comparing LD vs. CJL. Discussion: Chronic misalignment of feeding/fasting rhythm leads to metabolic disturbances generating nocturnal hyperglycemia, glucose intolerance and hyperinsulinemia in a IPGTT, increased LDL cholesterolemia, and increased weight gain, underscoring the importance of the timing of food consumption with respect to the circadian system for metabolic health.
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INTRODUCCIÓN: Para mitigar la propagación del SARS-CoV-2 se requirió de un confinamiento generalizado. Las autoridades argentinas impusieron aislamiento social preventivo durante 234 días (20 de marzo al 9 de noviembre de 2020), modificando el estilo de vida de la población. OBJETIVOS: Examinar la influencia de las medidas de bloqueo en el perfil metabólico de pacientes infectados por VIH en Argentina. PACIENTES Y MÉTODOS: Estudio de cohorte retrospectivo de 10.239 pacientes en seguimiento en una clínica de atención privada de personas con infección por VIH. Se incluyeron pacientes adultos con terapia antirretroviral (TARV) en curso que tuvieran una determinación de glucemia, colesterol total, colesterol HDL y trigliceridemia antes de la cuarentena (Pre-C: segundo semestre 2019) y una segunda determinación durante la misma (Intra-C: mayo 2020). Se excluyeron los pacientes con cambios en la TARV con impacto metabólico, los que iniciaron o suspendieron hipolipemiantes o hipoglucemiantes y mujeres embarazadas. Las variables categóricas se compararon mediante la prueba de la χ2 o la prueba exacta de Fisher y las continuas mediante la prueba t o la prueba de Mann-Whitney según correspondiera. Se consideró significativo un valor de p a dos colas < 0,05. RESULTADOS: Se incluyeron 540 individuos. La mediana de edad fue de 47 años y 74,6% fueron de sexo masculino. La mediana de índice de masa corporal fue 26,1 y 94,6% tenían bajo riesgo cardiovascular. Hubo un aumento significativo en el porcentaje de pacientes con hiperglucemia (Pre-C 5,2% vs Intra-C 8,5%, p 0,04), hipertrigliceridemia (Pre-C 33,9% vs Intra-C 40,7%, p 0,02) e hipercolesterolemia LDL (Pre-C 12,6% vs Intra-C 17,2%, p 0,04). CONCLUSIÓN: Nuestros resultados sugieren que la cuarentena, al menos en sus fases iniciales, puede tener un impacto negativo en el perfil metabólico de esta población.
BACKGROUND: The spread of SARS-CoV-2 required widespread lockdown to mitigate the pandemic. Argentine authorities imposed preventive social isolation for 234 days (March 20th to November 9th 2020). This measure led to major changes in the population's lifestyle. AIM: To examine the influence of COVID-19 lockdown measures on the metabolic profile of HIV-infected patients in Argentina. METHODS: Retrospective cohort study of 10,239 HIV-infected patients under follow up in a private clinic for HIV care. Adult patients with ongoing antiretroviral therapy (ART) and a baseline determination of blood glucose, total cholesterol, HDL-cholesterol and triglycerides done before lockdown (BL: second semester of 2019) and a second determination during lockdown (DL: May 2020) were included. Patients with recent changes in ART that may have metabolic impact, those starting lipid/glucose lowering agents and pregnant women were excluded. Categorical variables were compared using the χ2 test or Fisher's exact test, and continuous variables using the t-test or the Mann-Whitney test. A two-tailed value of p < 0.05 was considered significant. RESULTS: 540 individuals were included, median of age was 47 years and 74.6% were male. Median body mass index was 26.1 and 94.6% had low cardiovascular risk. There was a significant increase in the percentage of patients that met criteria for hyperglycemia (BL 4.8% and DL 8.5%, p < 0.001). We also observed significant (p < 0.001) increase in median (IQR) BL vs DL values in LDL-cholesterol [109 (90-128) vs 118 (97-139) mg/dL]; and triglycerides [120 (87-172) vs. 132 mg/dL (96-184)]. The proportion of patients with hyper-LDL cholesterolemia according to individual cardiovascular risk increased from 12.6 to 17.2% (p = 0.04). CONCLUSION: Our results suggest that quarantine, at least in its initial phases, may have a negative impact on the metabolic profile of this population.
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Humanos , Masculino , Feminino , Gravidez , Adulto , Pessoa de Meia-Idade , Idoso , Infecções por HIV/epidemiologia , Quarentena , COVID-19 , Argentina/epidemiologia , Triglicerídeos , Glicemia , Controle de Doenças Transmissíveis , Estudos Retrospectivos , Metaboloma , SARS-CoV-2 , HDL-ColesterolRESUMO
Introducción: Durante el ciclo de vida de los individuos son imprescindibles intervenciones para detectar y reducir el riesgo y las complicaciones de las enfermedades crónicas. Objetivo: Determinar la prevalencia de valores de riesgo vascular de los principales indicadores del metabolismo glucídico y lipídico en adolescentes y ancianos de La Habana. Métodos: Se realizó un estudio transversal en una muestra conformada por adolescentes (469 de 12-16 años) aparentemente sanos y ancianos (395 de 65-100 años) sin diagnóstico de enfermedades asociadas a la alteración marcada del estado nutricional y metabólico. Ambas poblaciones fueron evaluadas para glucosa, triglicéridos, colesterol total, colesterol de lipoproteinas de alta densidad y colesterol de lipoproteínas de baja densidad, séricos, mediante métodos enzimáticos convencionales. Se usaron rangos de riesgo referentes. Los resultados se analizaron mediante estadística descriptiva. Resultados: En los adolescentes evaluados, los triglicéridos (35,6 por ciento) y el colesterol total (23,9 por ciento) mostraron las mayores frecuencias de valores de riesgo. En las hembras ambos marcadores se mantuvieron como los más elevados en ese orden, mientras que, en los varones, la glucosa (25,5 por ciento) secundó a los triglicéridos como indicadores más alterados. En ancianos, al colesterol de lipoproteínas de baja densidad (58,2 por ciento) y al colesterol total (48,6 por ciento) correspondieron las mayores frecuencias de cifras de riesgo, patrón que se repitió en cada sexo. Los valores promedio de los indicadores fueron marcadamente superiores en ancianos que, en adolescentes, excepto para glucosa y colesterol de lipoproteínas de alta densidad. Conclusiones: Los resultados obtenidos muestran una elevada prevalencia de valores de riesgo vascular de varios indicadores metabólicos evaluados en adolescentes y ancianos, lo que sugiere la necesidad de monitorear los indicadores analizados e implementar intervenciones modificadoras de sus valores hacia la reducción del riesgo asociado, desde etapas tempranas, como las previas a la adolescencia(AU)
Introduction: During the life cycle of individuals, interventions are essential to detect and reduce the risk and complications of chronic diseases. Objective: To determine the prevalence of vascular risk values of the main indicators of carbohydrate and lipid metabolism in adolescents and elderlies in Havana. Methods: A cross-sectional study was carried out with a sample made up of apparently healthy adolescents (469; aged 12-16 years) and elderlies (395 aged 65-100 years) without a diagnosis of diseases associated with marked alteration of nutritional and metabolic status. Both populations were evaluated regarding serum glucose, triglycerides, total cholesterol, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol using conventional enzymatic methods. Reference risk ranges were used. The results were analyzed using descriptive statistics. Results: In the evaluated adolescents, triglycerides (35.6 percent) and total cholesterol (23.9 percent) showed the highest frequencies of risk values. In females, both markers remained the highest in that aspect; while in males, glucose (25.5 percent) accounted second after triglycerides as the most altered indicators. In the elderlies, low-density lipoprotein cholesterol (58.2 percent) and total cholesterol (48.6 percent) corresponded to the highest frequencies of risk values, a pattern that was repeated in each sex. The average values of the indicators were markedly higher in the elderlies than in adolescents, except for glucose and high-density lipoprotein cholesterol. Conclusions: The results obtained show high prevalence of vascular risk values of several metabolic indicators evaluated in adolescents and elderlies, which suggests the need to monitor the analyzed indicators and implement interventions to modify such values, in view of reducing the associated risk, from stages early, such as the pre-adolescence stage(AU)
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Humanos , Masculino , Feminino , Adolescente , Idoso , Doenças Vasculares/epidemiologia , Técnicas de Laboratório Clínico/métodos , Índice Glicêmico , Hiperlipidemias/tratamento farmacológico , Estudos TransversaisRESUMO
BACKGROUND: Micronutrient supplementation has been extensively explored as a strategy to improve health and reduce risk of chronic diseases. Fat-soluble vitamins like A and E with their antioxidant properties and mechanistic interactions with lipoproteins, have potentially a key impact on lipid metabolism and lipidemia. OBJECTIVE: The impact of micronutrients on lipid metabolism requires further investigation including characterization of plasma lipidome following supplementation and any cause-effect on circulating lipids. DESIGN: In this study, we elucidate the effect and associations of a multi-micronutrient intervention in Brazilian children and teens with lipoprotein alterations and lipid metabolism. RESULTS: Our analysis suggests a combination of short and long-term impact of supplementation on lipid metabolism, potentially mediated primarily by α-tocopherol (vitamin E) and retinol (vitamin A). Among the lipid classes, levels of phospholipids, lysophospholipids, and cholesterol esters were impacted the most along with differential incorporation of stearic, palmitic, oleic and arachidonic acids. Integrated analysis with proteomic data suggested potential links to supplementation-mediated alterations in protein levels of phospholipases and pyruvate dehydrogenase kinase 1 (PDK1). CONCLUSIONS: Associations between the observed differences in lipidemia, total triglyceride, and VLDL-cholesterol levels suggest that micronutrients may play a role in reducing these risk factors for cardiovascular disease in children. This would require further investigation.
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Suplementos Nutricionais , Hiperlipidemias/tratamento farmacológico , Lipídeos/sangue , Micronutrientes/administração & dosagem , Adolescente , Fatores Etários , Biomarcadores/sangue , Brasil , Criança , VLDL-Colesterol/sangue , Suplementos Nutricionais/efeitos adversos , Feminino , Humanos , Hiperlipidemias/sangue , Hiperlipidemias/diagnóstico , Lipidômica , Masculino , Micronutrientes/efeitos adversos , Proteômica , Fatores de Tempo , Resultado do Tratamento , Triglicerídeos/sangue , Vitamina A/administração & dosagem , alfa-Tocoferol/administração & dosagemRESUMO
This study aimed to explore lipoprotein metabolism in obstructive sleep apnea (OSA) and the effects of continuous positive airway pressure (CPAP). We studied 15 men with severe OSA [apnea-hypopnea index (AHI) ≥30 events/hour] and 12 age-, BMI-, and waist circumference-matched volunteers without OSA (AHI <5 events/hour). Carotid intima-media thickness (CIMT) was determined by a blind examiner. After 12 h fasting, a triglyceride-rich chylomicron-like emulsion, labeled with [14C]cholesteryl oleate and [3H]triolein, was injected intravenously followed by blood sample collection at preestablished times. Fractional clearance rate (FCR) of the radiolabeled lipids was estimated by compartmental analysis of radioisotope decay curves. Compared with controls, patients with OSA showed a significant delay in both cholesteryl ester FCR (0.0126 ± 0.0187 vs. 0.0015 ± 0.0025 min-1; P = 0.0313) and triglycerides FCR (0.0334 ± 0.0390 vs. 0.0051 ± 0.0074 min-1; P = 0.0001). CIMT was higher in the OSA group: 620 ± 17 vs. 725 ± 29 µm; P = 0.004. Cholesteryl ester FCRs were inversely related to total sleep time <90% (r = -0.463; P = 0.029) and CIMT (r = -0.601; P = 0.022). The triglyceride FCR was inversely correlated with AHI (r = -0.537; P = 0.04). In a subgroup of patients treated with CPAP for 3 months (n = 7), triglyceride FCR increased 5-fold (P = 0.025), but the cholesteryl ester FCR was unchanged. In conclusion, severe OSA decreased lipolysis of triglyceride-rich lipoproteins and delayed removal of remnants. CPAP treatment may be effective to restore the lipolysis rates.
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Pressão Positiva Contínua nas Vias Aéreas , Lipoproteínas/metabolismo , Apneia Obstrutiva do Sono/metabolismo , Apneia Obstrutiva do Sono/terapia , Triglicerídeos/metabolismo , Adulto , Feminino , Humanos , Lipólise , Lipoproteínas/sangue , Masculino , Sono , Apneia Obstrutiva do Sono/sangue , Triglicerídeos/sangueRESUMO
OBJECTIVE: It is not clear which phase of insulin secretion is more important to regulate lipoprotein lipase (LPL) activity. After a meal, insulin is released and acts as a major regulator of LPL activity. Postprandial hyperlipidemia is a common comorbidity in subjects with insulin resistance (IR). Therefore this study aimed to evaluate the role of the first-phase insulin secretion (FPIS) on postprandial lipidemia in subjects with IR and impaired glucose tolerance (IGT). RESEARCH DESIGN AND METHODS: This is a cross-sectional, observational and comparative study. We included male and female subjects between 40 and 60 years with a body mass index (BMI) between 23 and 30 kg/m2. Then, patients were divided into three groups. Group 1 consisted of control subjects with normal glucose tolerance and preserved FPIS. Group 2 included patients with IGT and a reduced FPIS. Group 3 consisted of subjects with IGT but normal FPIS. Both groups were paired by age and BMI with subjects in the control group. Subjects underwent an intravenous glucose tolerance test to classify each case, and then a load with a mixed meal load to measure postprandial lipidemia. RESULTS: A total of 32 subjects were evaluated: 10 were control subjects, 8 subjects with IGT with a reduced FPIS and 14 subjects with IGT and preserved FPIS. After administration of a standardized meal, group 2 showed a greater glucose area under the curve (AUC) at 30 and 120 min (p=0.001, for both). This group also showed a statistically significant increase (p<0.001) in triglyceride AUC. CONCLUSIONS: A reduced FPIS is significantly and independently associated with a larger postprandial hyperlipidemia in subjects with IGT.
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INTRODUCTION: Serum inflammatory cytokines derived from oral inflammation are associated with decreased insulin signaling (IS) and insulin resistance, which is a major risk factor for type 2 diabetes mellitus. This study aimed to investigate IS in the liver and skeletal muscle (SM) and disorders related to the serum lipid profile and glucose and insulin levels of nondiabetic rats with induced chronic periapical lesions (PLs). METHODS: Twenty-eight Wistar rats were divided into control and PL groups. PLs were induced by exposing the pulpal tissue to the oral environment. Experiments were conducted in both groups 30 days after pulp exposure. Maxillae were processed for histopathological analysis. IS was evaluated according to insulin receptor substrate (pp185-insulin receptor substrate 1 [IRS-1]/insulin receptor substrate 2 [IRS-2]) tyrosine phosphorylation status, IRS-1 serine phosphorylation status, and IRS-1 and IRS-2 content in the liver and SM by Western blotting. Serum total cholesterol, triglyceride, glucose, and insulin levels were measured enzymatically using a commercial kit. RESULTS: PL rats showed reduced pp185 P-Tyr and increased IRS-1 serine phosphorylation status in the SM but no change in the liver after insulin stimulation. No significant changes in IRS-1 and IRS-2 content, serum total cholesterol, triglyceride, glucose or insulin levels were noted. CONCLUSIONS: PLs are associated with decreased insulin signaling in the SM of rats. Because a decrease in insulin signaling is associated with insulin resistance, our results emphasize the importance of preventing local inflammatory diseases such as PLs to prevent alterations in IS in muscle.
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Polpa Dentária/lesões , Proteínas Substratos do Receptor de Insulina/metabolismo , Músculo Esquelético/metabolismo , Animais , Glicemia/metabolismo , Western Blotting , Colesterol/sangue , Polpa Dentária/patologia , Modelos Animais de Doenças , Hiperlipidemias/etiologia , Hiperlipidemias/metabolismo , Hiperlipidemias/patologia , Insulina/metabolismo , Fígado/metabolismo , Fígado/patologia , Músculo Esquelético/patologia , Fosforilação , Ratos Wistar , Triglicerídeos/sangue , Tirosina/metabolismoRESUMO
The observation that the fluidity must remain within a critical interval, outside which the stability and functionality of the cell tends to decrease, shows that stability, fluidity and function are related and that the measure of erythrocyte stability allows inferences about the fluidity or functionality of these cells. This study determined the biochemical and hematological variables that are directly or indirectly related to erythrocyte stability in a population of 71 volunteers. Data were evaluated by bivariate and multivariate analysis. The erythrocyte stability showed a greater association with hematological variables than the biochemical variables. The RDW stands out for its strong correlation with the stability of erythrocyte membrane, without being heavily influenced by other factors. Regarding the biochemical variables, the erythrocyte stability was more sensitive to LDL-C. Erythrocyte stability was significantly associated with RDW and LDL-C. Thus, the level of LDL-C is a consistent link between stability and functionality, suggesting that a measure of stability could be more one indirect parameter for assessing the risk of degenerative processes associated with high levels of LDL-C.