RESUMEN

Although there is an association between income status and concentration of perfluoroalkyl and polyfluoroalkyl substance (PFAS), the association remains uncertain in patients with hypertension, hyperlipidemia, and comorbidities. Data from the 2013-2016 National Health and Nutrition Examination Survey were analyzed. A total of 2665 adults were included, and the data included participants' serum PFAS (perfluorooctanoic acid [PFOA], perfluorononaic acid, perfluorodecanoic acid, perfluoroundecanoic acid, perfluorohexane sulfonic acid, and perfluorooctane sulfonic acid) levels and selected covariates. Multivariate linear regression models were used to examine the association between the ratio of family income to poverty (PIR) and individual serum PFAS concentrations in the hypertensive and/or hyperlipidemia groups after adjusting for covariates. The potential effects of sex and age on the results were explored using stratified analysis. A mediating effect model was used to explore the mediating effects of body mass index (BMI) and waist circumference on the association results. After adjusting for potential confounders, for hyperlipidemia and comorbidities (hypertension and hyperlipidemia), serum levels of multiple common PFAS increased by 0.09% (95%Confidence interval [CI] 0.02-0.15%) to 0.13% (95%CI 0.08-0.19%) and 0.10% (95%CI 0.02-0.17%) to 0.12% (95%CI 0.06-0.18%), respectively, with each 1% increase in PIR. The covariate model and stratified analyses results suggested the potential effects of different covariates such as age and sex, leading to changes in the statistical significance of the association results. BMI significantly mediated the effect of PIR on PFOA in hyperlipidemia (13%, P < 0.001). Household income in adults with hyperlipidemia and comorbidities positively correlated with serum PFAS concentration in the United States. Obesity played an indispensable mediating role in the association between economic income and PFAS concentration.

Asunto(s)

Fluorocarburos , Hiperlipidemias , Hipertensión , Humanos , Femenino , Masculino , Fluorocarburos/sangre , Hipertensión/sangre , Hipertensión/epidemiología , Persona de Mediana Edad , Adulto , Hiperlipidemias/sangre , Hiperlipidemias/epidemiología , Estados Unidos/epidemiología , Encuestas Nutricionales , Anciano , Ácidos Alcanesulfónicos/sangre , Índice de Masa Corporal , Caprilatos/sangre

RESUMEN

This study investigated osteoporosis risk factors among older Asian men with type-2 diabetes mellitus, hypertension, or hyperlipidaemia in primary care. Advanced age, dementia, depression, and polypharmacy were associated with higher risks for osteoporosis. Screening strategies targeting these factors are crucial for improving bone health as part of comprehensive preventive care. PURPOSE: Asian patients with type-2 diabetes mellitus (T2DM), hypertension, or hyperlipidaemia (DHL) are predominantly managed in primary care. They are also at risk of osteoporosis, but men are often under-screened and under-treated for this preventable bone disorder. This study aimed to identify the clinical characteristics and risk factors of osteoporosis among older men with DHL in primary care for early intervention. METHODS: This retrospective study included men aged 65 years and older managed in public primary care clinics for their DHL between 1st July 2017 and 30th June 2018. Demographic, clinical, laboratory, and imaging data were extracted from their electronic medical records based on their International Classification of Diseases-10 (ICD-10) diagnosis codes. Descriptive statistical analyses, with statistical significance set at p < 0.05, were conducted, followed by generalized estimating equation (GEE) modelling. RESULTS: Medical records of 17,644 men (83.1% Chinese, 16.9% minority ethnic groups, median age 71 years) were analysed. 2.3% of them had diagnosis of osteoporosis, 0.15% had fragility fracture, and 26.0% of those diagnosed with osteoporosis were treated with bisphosphonates. Their mean HbA1c was 6.9%; mean systolic and diastolic blood pressure were 133 and 69 mmHg. The GEE model showed that age (OR = 1.07, 95%CI = 1.05-1.09, p < 0.001), dementia (OR = 2.24, 95%CI = 1.33-3.77, p = 0.002), depression (OR = 2.38, 95%CI = 1.03-5.50, p = 0.043), and polypharmacy (OR = 6.85, 95%CI = 3.07-15.26, p < 0.001) were significantly associated with higher risks for osteoporosis. CONCLUSION: Age, dementia, depression, and polypharmacy are associated with osteoporosis risks in men with DHL. Strategies to incorporate osteoporosis screening among older men with these risk factors are needed to improve their bone health.

Asunto(s)

Diabetes Mellitus Tipo 2 , Hiperlipidemias , Hipertensión , Osteoporosis , Humanos , Masculino , Osteoporosis/epidemiología , Anciano , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/epidemiología , Factores de Riesgo , Estudios Retrospectivos , Hiperlipidemias/epidemiología , Hiperlipidemias/complicaciones , Hipertensión/tratamiento farmacológico , Hipertensión/complicaciones , Hipertensión/epidemiología , Anciano de 80 o más Años

RESUMEN

BACKGROUND: The role of fatty acids (FA) in the pathogenesis of insulin resistance and hyperlipidemia is a subject of intensive research. Several recent works have suggested cis-vaccenic acid (cVA) in plasma lipid compartments, especially in plasma phospholipids (PL) or erythrocyte membranes, could be associated with markers of insulin sensitivity and cardiovascular health. Nevertheless, not all the results of research work testify to these beneficial effects of cVA. Therefore, we decided to investigate the relations of proportion of cVA in plasma PL to markers of insulin resistance in hyperlipidemic men. SUBJECTS: In 231 men (median age 50) with newly diagnosed hyperlipidemia, we analyzed basic clinical parameters together with FA composition of plasma PL and stratified them according to the content of cVA into upper quartile (Q4) and lower quartile (Q1) groups. We examined also small control group of 50 healthy men. RESULTS: The individuals in Q4 differed from Q1 by lower plasma insulin (p < 0.05), HOMA-IR values (p < 0.01), and apolipoprotein B concentrations (p < 0.001), but by the higher total level of nonesterified FA (p < 0.01). Both groups had similar age, anthropometrical, and other lipid parameters. In plasma PL, the Q4 group had lower content of the sum of n-6 polyunsaturated FA, due to decrease of γ-linolenic and dihomo-γ-linolenic acids, whereas the content of monounsaturated FA (mainly oleic and palmitoleic) was in Q4 higher. CONCLUSIONS: Our results support hypothesis that plasma PL cVA could be associated with insulin sensitivity in men with hyperlipidemia.

Asunto(s)

Biomarcadores , Hiperlipidemias , Resistencia a la Insulina , Ácidos Oléicos , Fosfolípidos , Humanos , Masculino , Persona de Mediana Edad , Biomarcadores/sangre , Fosfolípidos/sangre , Hiperlipidemias/sangre , Adulto , Ácidos Oléicos/sangre , Insulina/sangre , Apolipoproteínas B/sangre

RESUMEN

Hyperlipidemia significantly contributes to the risk of developing cardiovascular diseases. However, about half of the patients do not adhere to their antihyperlipidemic medications, leading to healthcare costs and premature mortality. This study's objective was to determine the prevalence and associated factors of non-adherence to antihyperlipidemic medications. The study covered hypertensive patients (21,451) aged 21-75 years, presenting to the primary and secondary healthcare facilities across Pakistan (covering 21 divisions) from January 2022 to April 2023. The outcome intended was non-adherence to antihyperlipidemic medication, which was assessed by SEAMS and pill-counting methods (non-adherence < 80%). The study found overall non-adherence to antihyperlipidemic medication of 60.6% across Pakistan, with the highest non-adherence rates found in Azad Jammu and Kashmir (71.9%) and the lowest in Islamabad (47.7%). Multivariable logistic regression analysis revealed that female, no health card (Sehat Sahulat Program government insurance), < 5 years of illness, < 5 daily medications, and dose frequency of twice daily revealed a positively significant association with non-adherence. While monthly income 51,000-100,000, graduation level of education, Muhajir, and hyperlipidemia with one comorbid condition had a significant negative association with the non-adherence. Antihyperlipidemic non-adherence is a multifaceted, multifactorial, profound problem requiring a multipronged approach.

Asunto(s)

Hipolipemiantes , Cumplimiento de la Medicación , Humanos , Pakistán/epidemiología , Persona de Mediana Edad , Femenino , Masculino , Adulto , Cumplimiento de la Medicación/estadística & datos numéricos , Hipolipemiantes/uso terapéutico , Estudios Transversales , Anciano , Prevalencia , Hiperlipidemias/tratamiento farmacológico , Hiperlipidemias/epidemiología , Adulto Joven , Factores de Riesgo , Hipertensión/tratamiento farmacológico , Hipertensión/epidemiología

RESUMEN

Obesity and hyperlipidemia have become major disorders predominantly causing prevailing cardiovascular diseases and ultimately death. The prolonged use of anti-obesity drugs and statins for reducing obesity and blood lipid levels is leading toward adverse effects of kidneys and muscles, specifically rhabdomyolysis. The objective of this study is to evaluate potential of seeds of Ficus carica against hyperlipidemia. Various extracts and isolated compounds from fig seeds were analyzed and evaluated for their anti-hyperlipidemic potential. Methanol extract and its ethyl acetate fraction showed maximum pancreatic lipase inhibition of 61.93% and 86.45% in comparison to reference drug Orlistat. Four compounds isolated by HPLC-PDA technique were determined as Gallic acid, Catechin, Epicatechin, and Quercetin also showed strong potential to inhibit enzyme pancreatic lipase comparable to Orlistat. These isolated compounds were further analyzed for molecular docking and MM-GBSA studies. Three ligands, namely Quercetin, Epicatechin, and Catechin were found more effective against pancreatic lipase as these possessed docking scores (-9.881, -9.741, -9.410) higher to that of the reference ligand Orlistat (-5.273). The binding free energies of these compounds were -55.03, -56.54, and 60.35 kcal/mol, respectively. The results have shown that Quercetin has the highest binding affinity correlating with the highest inhibition of pancreatic lipase enzyme 1LPB. Hence, it is suggested that seeds of F. carica have promising anti-hyperlipidemic potential and foremost in reducing obesity.

Asunto(s)

Ficus , Hipolipemiantes , Simulación del Acoplamiento Molecular , Extractos Vegetales , Semillas , Ficus/química , Semillas/química , Extractos Vegetales/química , Extractos Vegetales/farmacología , Hipolipemiantes/farmacología , Hipolipemiantes/química , Hipolipemiantes/aislamiento & purificación , Lipasa/antagonistas & inhibidores , Lipasa/metabolismo , Humanos , Hiperlipidemias/tratamiento farmacológico

RESUMEN

Pinus koraiensis (PK) leaf extract, derived from Korean pine byproducts, holds promise for alleviating postprandial hyperlipidemia. In this study, we investigated the potential of PK leaf extract for modulating postprandial hyperlipidemia in adults with normal or borderline fasting triglyceride levels. In a randomized, double-blind, parallel design, 70 subjects were randomly assigned to either the placebo or PK group for 4 weeks. After 4 weeks of consuming PK leaf extract, the results indicated a trend toward decreased serum apolipoprotein B-100 (ApoB100) levels 2 h after a high-fat challenge. Furthermore, significant improvements were observed in the incremental area under the curve (iAUC) at 0-4 h and 2-4 h compared to baseline, particularly among individuals with a higher body weight (>61.35 kg) and daily caloric intake (>1276.5 kcal). Based on these findings, PK leaf extract may have beneficial effects on postprandial lipoprotein metabolism, especially among individuals with a relatively high body weight and caloric intake.

Asunto(s)

Apolipoproteína B-100 , Metabolismo de los Lípidos , Pinus , Extractos Vegetales , Hojas de la Planta , Periodo Posprandial , Humanos , Método Doble Ciego , Pinus/química , Masculino , Extractos Vegetales/farmacología , Hojas de la Planta/química , Femenino , Adulto , Apolipoproteína B-100/sangre , Metabolismo de los Lípidos/efectos de los fármacos , Persona de Mediana Edad , Dieta Alta en Grasa , Triglicéridos/sangre , Adulto Joven , Voluntarios Sanos , Hiperlipidemias/tratamiento farmacológico , Hiperlipidemias/sangre

RESUMEN

OBJECTIVE: Both Roux-en-Y gastric bypass (RYGB) and laparoscopic sleeve gastrectomy (LSG) are effective at inducing weight loss, but more information is needed on their comparative effectiveness at improving clinical/biochemical outcomes related to the presence of hyperlipidemia, metabolic dysfunction-associated steatotic liver disease (MASLD), or type 2 diabetes (T2D) at baseline. Here we aimed to assess this in real-world practice. METHODS: This is a prospective cross-sectional and cohort study of 142 patients who underwent RYGB or LSG as per clinical practice. Clinical/biochemical data were collected at baseline, prior to surgery and 12 months post-bariatric surgery. Liver biopsy was performed during surgery to diagnose MASLD. The main outcome was 12-month changes in lipid parameters, mainly total cholesterol, between types of surgery. RESULTS: A TOTAL OF: 107 participants underwent RYGB and 35 underwent LSG. Both groups were similar at baseline except for a higher proportion of males and waist circumference in the LSG group. At 12 months postsurgery, RYGB versus LSG resulted in a significantly lower body mass index, triglycerides, total cholesterol, and low-density lipoprotein. However, alanine aminotransferase was significantly lower in those who underwent LSG. In subgroup analyses RYGB was superior at improving lipid-related parameters in those with hyperlipidemia, whereas LSG was superior at reducing alanine aminotransferase in those with MASLD. CONCLUSIONS: RYGB versus LSG leads to greater reductions in body mass index and lipid parameters, especially in those with hyperlipidemia, whereas LSG showed greater improvements in liver enzymes in those with MASLD.

Asunto(s)

Diabetes Mellitus Tipo 2 , Gastrectomía , Derivación Gástrica , Hiperlipidemias , Humanos , Masculino , Femenino , Diabetes Mellitus Tipo 2/metabolismo , Hiperlipidemias/etiología , Estudios Prospectivos , Derivación Gástrica/métodos , Estudios Transversales , Persona de Mediana Edad , Adulto , Gastrectomía/métodos , Hígado Graso/etiología , Índice de Masa Corporal , Pérdida de Peso , Resultado del Tratamiento , Obesidad Mórbida/cirugía , Obesidad Mórbida/metabolismo , Obesidad Mórbida/complicaciones , Laparoscopía/métodos , Estudios de Cohortes

RESUMEN

BACKGROUND: Hyperlipidemia is one of the main causes of aggravated hepatic ischemia-reperfusion injury (IRI). Simvastatin (SIM), a lipid-lowering drug, has been shown to effectively alleviate IRI caused by hyperlipidemia. However, the regulatory mechanism by which SIM alleviates hyperlipidemia-induced hepatic IRI is still not clear. This study aims to explore the potential mechanisms of SIM in inhibiting hyperlipidemia-induced hepatic IRI, providing new therapeutic strategies for the alleviation of hepatic IRI. METHODS: An animal model of hyperlipidemia was induced by feeding mice a high-fat diet for 8 weeks. Subsequently, a hepatic IRI animal model of hyperlipidemia was established by occluding the hepatic artery and portal vein for one hour, followed by reperfusion for 6 or 12 h. Enzyme linked immunosorbent assay, Western blotting, hematoxylin-eosin (H&E) staining, immunohistochemistry, immunofluorescence, and Terminal-deoxynucleoitidyl Transferase Mediated Nick End Labeling assay, were used to evaluate liver injury, neutrophil extracellular traps (NETs) formation, and related molecular mechanisms. RESULTS: Hepatic IRI was accelerated by hyperlipidemia, which enhanced the expression of oxidized low-density lipoprotein (oxLDL) and Macrophage-1antigen (Mac-1), leading to the promotion of NETs formation and apoptosis of liver cells. The administration of simvastatin reduced the levels of oxLDL and Mac-1, decreased the formation of NETs, and alleviated hepatic IRI induced by hyperlipidemia. CONCLUSIONS: Simvastatin reduced hyperlipidemia-induced hepatic IRI by inhibiting the formation of NETs through the regulation of the oxLDL/Mac-1 pathway.

Asunto(s)

Dieta Alta en Grasa , Trampas Extracelulares , Hiperlipidemias , Hígado , Daño por Reperfusión , Simvastatina , Animales , Simvastatina/farmacología , Simvastatina/uso terapéutico , Daño por Reperfusión/prevención & control , Daño por Reperfusión/patología , Daño por Reperfusión/tratamiento farmacológico , Daño por Reperfusión/metabolismo , Ratones , Trampas Extracelulares/efectos de los fármacos , Trampas Extracelulares/metabolismo , Masculino , Dieta Alta en Grasa/efectos adversos , Hígado/patología , Hígado/efectos de los fármacos , Hígado/metabolismo , Hiperlipidemias/tratamiento farmacológico , Hiperlipidemias/metabolismo , Hiperlipidemias/patología , Hiperlipidemias/complicaciones , Ratones Endogámicos C57BL , Modelos Animales de Enfermedad , Lipoproteínas LDL/metabolismo , Transducción de Señal/efectos de los fármacos , Apoptosis/efectos de los fármacos

RESUMEN

The ketogenic diet (KD) is a high-fat, low-carbohydrate diet that results in the elevation of serum ketone bodies, known as ketosis. This metabolic consequence has been suggested as a method for treating neurological conditions, improving exercise performance, and facilitating weight loss for overweight individuals. However, since most research primarily uses male populations, little is known about the potential sex differences during the consumption of the KD. In addition, the effects of the KD on aging are relatively unexplored. Therefore, the purpose of this study was to explore sex- and age-specific differences in mice fed the KD. Male and female C57BL/6N mice at either 12 wks or 24 wks of age were randomly assigned to a KD (90% fat, 1% carbohydrate) or chow (13% fat, 60% carbohydrate) group for 6 wks. KD induced weight gain, increased adiposity, induced hyperlipidemia, caused lipid accumulation in the heart and liver, and led to glycogen depletion in the heart, liver, and muscle with varying degrees of changes depending on age and sex. While younger and older male mice on the KD were prone to glucose intolerance, the KD acutely improved rotarod performance in younger females. Overall, this study highlights potential sex and aging differences in the adaptation to the KD.

Asunto(s)

Dieta Cetogénica , Hígado , Ratones Endogámicos C57BL , Animales , Masculino , Femenino , Factores Sexuales , Hígado/metabolismo , Ratones , Factores de Edad , Adiposidad , Envejecimiento/fisiología , Glucógeno/metabolismo , Aumento de Peso , Hiperlipidemias/dietoterapia , Hiperlipidemias/etiología , Metabolismo de los Lípidos , Intolerancia a la Glucosa , Caracteres Sexuales , Músculo Esquelético/metabolismo , Miocardio/metabolismo

RESUMEN

AIMS: Widespread brain metabolite abnormalities in those with alcohol use disorder (AUD) were reported in numerous studies, but the effects of the pro-atherogenic conditions of hypertension, type 2 diabetes mellitus, hepatitis C seropositivity, and hyperlipidemia on metabolite levels were not considered. These conditions were associated with brain metabolite abnormalities in those without AUD. We predicted treatment-seeking individuals with AUD and pro-atherogenic conditions (Atherogenic+) demonstrate lower regional metabolite markers of neuronal viability [N-acetylaspartate (NAA)] and cell membrane turnover/synthesis [choline-containing compounds (Cho)], compared with those with AUD without pro-atherogenic conditions (Atherogenic-) and healthy controls (CON). METHODS: Atherogenic+ (n = 59) and Atherogenic- (n = 51) and CON (n = 49) completed a 1.5 T proton magnetic resonance spectroscopic imaging study. Groups were compared on NAA, Cho, total creatine, and myoinositol in cortical gray matter (GM), white matter (WM), and select subcortical regions. RESULTS: Atherogenic+ had lower frontal GM and temporal WM NAA than CON. Atherogenic+ showed lower parietal GM, frontal, parietal and occipital WM and lenticular nuclei NAA level than Atherogenic- and CON. Atherogenic- showed lower frontal GM and WM NAA than CON. Atherogenic+ had lower Cho level than CON in the frontal GM, parietal WM, and thalamus. Atherogenic+ showed lower frontal WM and cerebellar vermis Cho than Atherogenic- and CON. CONCLUSIONS: Findings suggest proatherogenic conditions in those with AUD were associated with increased compromise of neuronal integrity and cell membrane turnover/synthesis. The greater metabolite abnormalities observed in Atherogenic+ may relate to increased oxidative stress-related compromise of neuronal and glial cell structure and/or impaired arterial vasoreactivity/lumen viability.

Asunto(s)

Alcoholismo , Aterosclerosis , Encéfalo , Humanos , Masculino , Femenino , Persona de Mediana Edad , Alcoholismo/metabolismo , Alcoholismo/patología , Encéfalo/metabolismo , Encéfalo/diagnóstico por imagen , Adulto , Aterosclerosis/metabolismo , Ácido Aspártico/análogos & derivados , Ácido Aspártico/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Colina/metabolismo , Hipertensión/metabolismo , Hiperlipidemias/metabolismo , Inositol/metabolismo , Espectroscopía de Resonancia Magnética , Creatina/metabolismo

RESUMEN

Hyperlipidemic pancreatitis (HP) is an inflammatory injury of the pancreas triggered by elevated serum triglyceride (TG) levels. The mechanistic target of rapamycin (mTOR) signaling pathway plays a crucial role in regulating lipid homeostasis and inflammation. This study aimed to investigate whether the activity of mTOR complex 2 (mTORC2) affects the progression of HP and its underlying mechanisms. In vivo, a high-fat diet and retrograde administration of sodium taurocholate were employed to establish the HP models in rats, with pancreatic tissue pathology evaluated. The expression of Rictor and peroxisome proliferator-activator receptor (PPAR) was examined. The serum levels of TG, fatty acid metabolites, inflammatory and lipid metabolism-related factors were determined. In vitro, pancreatic acinar cells (PACs) were exposed to palmitic acid and cholecystokinin-8. PAC apoptosis, pyroptosis, and ferroptosis were assessed. In the HP models, rats and PACs exhibited upregulated Rictor and downregulated PPARα, and Rictor knockdown promoted PPARα expression. In vivo, Rictor knockdown decreased the serum levels of TG, α-amylase, total cholesterol, low-density lipoprotein cholesterol, lactate dehydrogenase, and inflammatory factors, while increasing high-density lipoprotein cholesterol levels. Rictor knockdown increased ACOX1 and CPT1α and decreased SREBP-1, CD36, SCD1, ACLY, and ACACA. Rictor knockdown reduced damage to pancreatic tissue structure. In vitro, Rictor knockdown inhibited PAC apoptosis, pyroptosis, and ferroptosis. Treatment with the PPARα antagonist GW6471 abolished the beneficial effects of Rictor knockdown. Rictor/mTORC2 deficiency reduces serum TG levels, maintains lipid homeostasis, and suppresses inflammation by inhibiting PPARα expression. Weakening mTORC2 activity holds promise as a novel therapeutic strategy for HP.

Asunto(s)

Hiperlipidemias , Metabolismo de los Lípidos , Diana Mecanicista del Complejo 2 de la Rapamicina , PPAR alfa , Pancreatitis , Ratas Sprague-Dawley , Animales , PPAR alfa/metabolismo , PPAR alfa/genética , Ratas , Pancreatitis/metabolismo , Pancreatitis/patología , Pancreatitis/inducido químicamente , Pancreatitis/genética , Hiperlipidemias/metabolismo , Hiperlipidemias/genética , Metabolismo de los Lípidos/efectos de los fármacos , Masculino , Diana Mecanicista del Complejo 2 de la Rapamicina/metabolismo , Técnicas de Silenciamiento del Gen

RESUMEN

Hyperlipidemia and hypertension might play a role in cardiac fibrosis, in which a heterogeneous population of fibroblasts seems important. However, it is unknown whether CD34+ progenitor cells are involved in the pathogenesis of heart fibrosis. This study aimed to explore the mechanism of CD34+ cell differentiation in cardiac fibrosis during hyperlipidemia. Through the analysis of transcriptomes from 50,870 single cells extracted from mouse hearts and 76,851 single cells from human hearts, we have effectively demonstrated the evolving cellular landscape throughout cardiac fibrosis. Disturbances in lipid metabolism can accelerate the development of fibrosis. Through the integration of bone marrow transplantation models and lineage tracing, our study showed that hyperlipidemia can expedite the differentiation of non-bone marrow-derived CD34+ cells into fibroblasts, particularly FABP4+ fibroblasts, in response to angiotensin II. Interestingly, the partial depletion of CD34+ cells led to a notable reduction in triglycerides in the heart, mitigated fibrosis, and improved cardiac function. Furthermore, immunostaining of human heart tissue revealed colocalization of CD34+ cells and fibroblasts. Mechanistically, our investigation of single-cell RNA sequencing data through pseudotime analysis combined with in vitro cellular studies revealed the crucial role of the PPARγ/Akt/Gsk3ß pathway in orchestrating the differentiation of CD34+ cells into FABP4+ fibroblasts. Through our study, we generated valuable insights into the cellular landscape of CD34+ cell-derived cells in the hypertrophic heart with hyperlipidemia, indicating that the differentiation of non-bone marrow-derived CD34+ cells into FABP4+ fibroblasts during this process accelerates lipid accumulation and promotes heart failure via the PPARγ/Akt/Gsk3ß pathway.

Asunto(s)

Antígenos CD34 , Diferenciación Celular , Proteínas de Unión a Ácidos Grasos , Fibroblastos , Fibrosis , Metabolismo de los Lípidos , Fibroblastos/metabolismo , Fibroblastos/patología , Humanos , Ratones , Animales , Antígenos CD34/metabolismo , Proteínas de Unión a Ácidos Grasos/metabolismo , Proteínas de Unión a Ácidos Grasos/genética , Miocardio/metabolismo , Miocardio/patología , Proteínas Proto-Oncogénicas c-akt/metabolismo , Hiperlipidemias/metabolismo , Hiperlipidemias/patología , Masculino , Transducción de Señal , PPAR gamma/metabolismo , Glucógeno Sintasa Quinasa 3 beta/metabolismo , Modelos Animales de Enfermedad

RESUMEN

Dysregulation of the hematopoietic niche during hyperlipidemia facilitates pathologic leukocyte production, driving atherogenesis. Although definitive hematopoiesis occurs primarily in the bone marrow, during atherosclerosis this also occurs in the spleen. Cells of the bone marrow niche, particularly endothelial cells, have been studied in atherosclerosis, although little is known about how splenic endothelial cells respond to the atherogenic environment. Here we show unique dysregulated pathways in splenic compared to bone marrow endothelial cells during atherosclerosis, including perturbations of lipid metabolism and endocytic trafficking pathways. As part of this response, we identify the mixed lineage kinase domain-like (MLKL) protein as a repressor of splenic, but not bone marrow, myelopoiesis. Silencing MLKL in splenic endothelial cells results in inefficient endosomal trafficking and lipid accumulation, ultimately promoting the production of myeloid cells that participate in plaque development. These studies identify endocytic trafficking by MLKL as a key mechanism of splenic endothelial cell maintenance, splenic hematopoiesis and, subsequently, atherosclerosis.

Asunto(s)

Aterosclerosis , Células Endoteliales , Hiperlipidemias , Proteínas Quinasas , Bazo , Bazo/patología , Bazo/metabolismo , Proteínas Quinasas/metabolismo , Proteínas Quinasas/genética , Células Endoteliales/metabolismo , Células Endoteliales/patología , Animales , Aterosclerosis/patología , Aterosclerosis/metabolismo , Hiperlipidemias/metabolismo , Hiperlipidemias/patología , Ratones Endogámicos C57BL , Modelos Animales de Enfermedad , Masculino , Mielopoyesis , Humanos , Células Cultivadas , Metabolismo de los Lípidos , Ratones , Placa Aterosclerótica/patología , Placa Aterosclerótica/metabolismo , Ratones Noqueados para ApoE , Endocitosis/fisiología , Endosomas/metabolismo , Nicho de Células Madre/fisiología

RESUMEN

Monascus has the ability to produce secondary metabolites, such as monacolin K (MK), known for its physiological functions, including lipid-lowering effects. Widely utilized in industries such as health food and medicine, MK is a significant compound derived from Monascus. Quinoa, recognized by the Food and Agriculture Organization of the United Nations as "the only plant food that can meet human basic nutritional needs by itself", possesses dual advantages of high nutritional value and medicinal food homology. This study employed animal experiments to investigate the hypolipidemic activity of Monascus-fermented quinoa (MFQ) and explored the molecular mechanism underlying the lipid-lowering effect of MFQ on hyperlipidemic mice through transcriptomic and metabolomic analyses. The results demonstrated that high-dose MFQ intervention (1600 mg kg-1 d-1) effectively decreased weight gain in hyperlipidemic mice without significant changes in cardiac index, renal index, or spleen index. Moreover, hepatic steatosis in mice was significantly improved. Serum levels of total cholesterol, triglycerides, and low-density lipoprotein cholesterol were markedly reduced, demonstrating that the lipid-lowering effect of MFQ was comparable to the drug control lovastatin. Conversely, both low-dose MFQ (400 mg kg-1 d-1) and unfermented quinoa exhibited no significant lipid-lowering effect. Integrated analysis of the transcriptome and metabolome suggested that MFQ may regulate amino acid levels in hyperlipidemic mice by influencing metabolic pathways such as phenylalanine, tyrosine, and tryptophan metabolism. This regulation alleviates hyperlipidemia induced by a high-fat diet, resulting in a significant reduction in blood lipid levels in mice.

Asunto(s)

Aminoácidos , Chenopodium quinoa , Hiperlipidemias , Monascus , Animales , Monascus/metabolismo , Hiperlipidemias/tratamiento farmacológico , Hiperlipidemias/metabolismo , Ratones , Chenopodium quinoa/química , Masculino , Aminoácidos/metabolismo , Fermentación , Ratones Endogámicos C57BL , Hipolipemiantes/farmacología , Triglicéridos/metabolismo , Triglicéridos/sangre , Alimentos Fermentados/microbiología

RESUMEN

Hyperlipidemia is associated with intestinal barrier dysfunction and gut microbiota dysbiosis. Here, we aimed at investigating whether epicatechin (EC) and ß-glucan (BG) from whole highland barley grain alleviated hyperlipidemia associated with ameliorating intestinal barrier dysfunction and modulating gut microbiota dysbiosis in high-fat-diet-induced mice. It was observed that EC and BG significantly improved serum lipid disorders and up-regulated expression of PPARα protein and genes. Supplementation of EC and BG attenuated intestinal barrier dysfunction via promoting goblet cells proliferation and tight junctions. Supplementation of EC and BG prevented high fat diet-induced gut microbiota dysbiosis via modulating the relative abundance of Ruminococcaceae, Lactobacillus, Desulfovibrio, Lactococcus, Allobaculum and Akkermansia, and the improving of short chain fatty acid contents. Notably, combination of EC and BG showed synergistic effect on activating PPARα expression, improving colonic physical barrier dysfunction and the relative abundance of Lactobacillus and Desulfovibrio, which may help explain the effect of whole grain highland barley on alleviating hyperlipidemia.

Asunto(s)

Catequina , Dieta Alta en Grasa , Microbioma Gastrointestinal , Hordeum , Hiperlipidemias , beta-Glucanos , Animales , Microbioma Gastrointestinal/efectos de los fármacos , Hordeum/química , beta-Glucanos/farmacología , beta-Glucanos/química , Hiperlipidemias/tratamiento farmacológico , Dieta Alta en Grasa/efectos adversos , Ratones , Catequina/farmacología , Masculino , Mucosa Intestinal/metabolismo , Mucosa Intestinal/efectos de los fármacos , Disbiosis/tratamiento farmacológico , PPAR alfa/metabolismo , PPAR alfa/genética , Granos Enteros/química , Ratones Endogámicos C57BL

RESUMEN

Hyperlipidemia, an elevated level of cholesterol and/or triglycerides, has become a major public health problem worldwide. Although drugs intervention is effective in treating hyperlipidemia, most of them have adverse side effects. Peptides from natural plants with high anti-hyperlipidemic activity and a strong safety profile have emerged as promising candidates to prevent and ameliorate hyperlipidemia. This review summarizes the recent advances in plant-derived anti-hyperlipidemic peptides in terms of their sources, production, purification, identification, and activity evaluation. The focus is extended to their potential anti-hyperlipidemic mechanisms and structure-function relationships. Bioactive peptides derived from various plant sources, especially peptides containing hydrophobic and/or acidic amino acids, have shown remarkable effects in hyperlipidemic treatment. Their anti-hyperlipidemic effects are mediated by various mechanisms, including regulation of cholesterol metabolism and triglyceride metabolism, inhibition of inflammation-related metabolic syndrome, and modulation of the gut microbiota. Further evaluation of the stability, bioavailability, and clinical efficacy of these peptides is recommended.

Asunto(s)

Hiperlipidemias , Hipolipemiantes , Péptidos , Humanos , Hipolipemiantes/química , Hipolipemiantes/farmacología , Hiperlipidemias/tratamiento farmacológico , Hiperlipidemias/metabolismo , Péptidos/química , Péptidos/farmacología , Animales , Relación Estructura-Actividad , Extractos Vegetales/química , Extractos Vegetales/farmacología , Colesterol/metabolismo , Proteínas de Plantas/química , Proteínas de Plantas/farmacología , Plantas/química

RESUMEN

BACKGROUND: In patients with hyperlipidemia, the risk of retear increases after rotator cuff repair (RCR). In particular, it has been reported that preoperative low-density lipoprotein cholesterol (LDL-C) level affects cuff integrity. However, there are no studies assessing whether lipidemic control affects cuff healing. PURPOSE: To evaluate the effect of preoperative lipidemic control on cuff integrity after arthroscopic RCR across cardiovascular disease risk groups in patients with hyperlipidemia. STUDY DESIGN: Case-control study; Level of evidence, 3. METHODS: The authors retrospectively reviewed the charts of patients with hyperlipidemia who underwent arthroscopic double-row suture bridge RCR between 2014 and 2019. The included patients had LDL-C tested within 1 month before surgery. Magnetic resonance imaging was conducted 6 months after surgery to evaluate the integrity of the repaired cuff tendon. Patients were divided into groups of low, moderate, high, and very high risk according to the 4th Korean Dyslipidemia Guidelines. On the basis of the target LDL-C set in each risk group, patients were categorized into 2 groups: group C (controlled hyperlipidemia, less than target LDL-C) and group U (uncontrolled hyperlipidemia, target LDL-C or greater). The correlation between serum lipid profile, lipidemic control, and post-RCR integrity was evaluated. RESULTS: A total of 148 patients were analyzed, 51 in group U and 97 in group C. The retear rate was significantly higher in group U than in group C (23/51 [45.1%] vs 18/97 [18.6%], respectively; P = .001). The proportion of group U was significantly higher in the retear group than in the healing group (56.1% vs 26.2%; P = .001). In addition, the proportions of patients with uncontrolled diabetes mellitus (DM) (19.5% vs 3.7%; P = .002) and mediolateral (2.6 ± 1.2 cm vs 1.7 ± 1.1 cm; P < .001) and anteroposterior (2.2 ± 1.1 cm vs 1.6 ± 0.8 cm; P = .003) tear sizes were significantly different between the retear and healing groups, respectively. No significant difference in serum lipid profile, including LDL-C level (119.6 ± 31.3 vs 116.7 ± 37.2; P = .650), was observed between the retear and healing groups. Multivariate regression analysis identified uncontrolled hyperlipidemia (OR, 4.005; P = .001), uncontrolled DM (OR, 5.096; P = .022), and mediolateral tear size (OR, 1.764; P = .002) as independent risk factors for retear. The 2.0-cm mediolateral size cutoff and the 3 independent risk factors had significant associations with retear. CONCLUSION: Poor preoperative lipidemic control was significantly associated with poor healing after RCR. In addition to large mediolateral tear size, uncontrolled hyperlipidemia and DM were significant risk factors for retear. Moreover, poor lipidemic control compared with the recommended target level before surgery was more correlated with an increased retear rate than a preoperative LDL-C level.

Asunto(s)

LDL-Colesterol , Hiperlipidemias , Lesiones del Manguito de los Rotadores , Humanos , Lesiones del Manguito de los Rotadores/cirugía , Masculino , Persona de Mediana Edad , Femenino , Estudios Retrospectivos , Estudios de Casos y Controles , LDL-Colesterol/sangre , Anciano , Artroscopía , Imagen por Resonancia Magnética , Factores de Riesgo

RESUMEN

STUDY OBJECTIVE: Hyperlipidemia and postoperative delirium (POD) significantly affect patients' quality of life; however, the question of whether hyperlipidemia constitutes a risk factor for POD remain unclear. This study aimed to investigate whether patients with hyperlipidemia face elevated risks of developing POD and to identify potential causes for this increased risk. DESIGN: A prospective cohort study. SETTING: Operating room. PATIENTS: Patients were adults scheduled for colorectal cancer surgery in 2023. EXPOSURES: The exposure factor was hyperlipidemia, and the patients were divided into hyperlipidemia group and non-hyperlipidemia group. MEASUREMENTS: POD occurrence within three days post-surgery was assessed using the 3-Minute Diagnostic Interview for Confusion Assessment Method. Over one year, these patients were monitored through telephone to evaluate their survival and cognitive function. Logistic regression analysis was performed to evaluate the risk factors for POD development in patients with hyperlipidemia and to construct a clinical prediction model. MAIN RESULTS: This study included 555 patients. POD incidence was 21.6% in the hyperlipidemia group and 12.7% in the non-hyperlipidemia group. One year following surgery, patients with hyperlipidemia and POD exhibited significantly higher rates of mortality and cognitive decline than did those without POD (p < 0.001). A multifactorial logistic clinical prediction model was constructed from seven independent risk factors for POD development in patients with hyperlipidemia, including education, preoperative total cholesterol (TC), preoperative triglyceride (TG), diet, history of hypertension, Sedation-Agitation Scale, and postoperative trimethylamine N-oxide expression level, and it had the highest predictive value for POD development in patients with hyperlipidemia. CONCLUSIONS: Compared with those without hyperlipidemia, patients with hyperlipidemia had higher POD incidence. Elevated serum TC and TG levels are independent risk factors for POD in patients with hyperlipidemia. The study's findings could help develop strategies for improving POD and hyperlipidemia treatment.

Asunto(s)

Delirio , Hiperlipidemias , Complicaciones Posoperatorias , Humanos , Hiperlipidemias/epidemiología , Estudios Prospectivos , Masculino , Femenino , Factores de Riesgo , Persona de Mediana Edad , Anciano , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Delirio/epidemiología , Delirio/etiología , Incidencia , Neoplasias Colorrectales/cirugía , Estudios de Cohortes

Asunto(s)

Hiperlipidemias , Complicaciones Posoperatorias , Humanos , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/epidemiología , Estudios Prospectivos , Delirio del Despertar/prevención & control , Delirio del Despertar/etiología , Delirio del Despertar/epidemiología , Delirio del Despertar/diagnóstico , Factores de Riesgo , Delirio/etiología , Delirio/prevención & control

RESUMEN

BACKGROUND: This study aimed to compare the lipemia removal efficiency of highspeed centrifugation, lipid scavengers, and dilution for biochemical analytes. METHODS: We collected 30 cases of lipemic plasma in an emergency laboratory and divided them into 4 aliquots. Lipemia was removed by highspeed centrifugation, lipid scavenger, dilution, and ultracentrifugation, then analytes were measured by an AU5800 analyzer. Taking ultracentrifugation as reference, the efficiencies of the other three methods were evaluated based on the deviation. RESULTS: When highspeed centrifugation was used for lipemia removal, DBIL (18.62%), and Magnesium (6.09%) could not satisfy the criterion. When lipid scavengers were applied to remove lipemia, CRP (-86.70%), TP (-8.29%), CKMB (-44.85%), DBIL (37.96%), Glu (4.20%) and phosphate (14.32%) were not suggested as lipid scavengers. For dilution, nearly half of the analytes could satisfy the criterion, including AMY (2.41%), CRP (5.54%), ALT (2.85%), GGTL (-1.73%), ALP (-0.04%), Glu (-0.84%), LDH (0.06%), CK (0.68%), BUN (3.80%), CREA (-1.54%), UA (5.42%), and magnesium (0.43%). CONCLUSIONS: Neither of the methods for lipid removal could satisfy all emergency department tests for lipid removal. This finding suggests that removing lipemia in the clinical laboratory should be based on the characteristics and the method of testing.

Asunto(s)

Hiperlipidemias , Humanos , Hiperlipidemias/sangre , Hiperlipidemias/diagnóstico , Centrifugación/métodos , Ultracentrifugación/métodos , Masculino , Femenino , Persona de Mediana Edad , Adulto , Lípidos/sangre