Aims: Cholesterol plays an essential role in membrane structure and function, being especially important in the brain. Alteration of brain cholesterol synthesis and metabolism has been demonstrated in several Huntington's disease (HD) mouse and cell models; however, less is known about these alterations in human tissue. This study aimed to identify alterations to cholesterol synthetic and metabolic pathways in human HD brain tissue.
Methods: A broad range of cholesterol synthetic precursors, metabolites and oxidation products were measured by gas chromatography-tandem mass spectrometry in five regions of human post mortem HD brain and compared with age- and sex-matched control tissues. The level of enzymes that regulate cholesterol homeostasis, cholesterol 24-hydroxylase and delta(24)-sterol reductase were investigated by Western blotting and qPCR in putamen.
Results: The most significant changes were localized to the putamen, where a 60% decrease in 24(S)-hydroxycholesterol, 30% increase in cholesterol and 100-200% increase in synthetic precursors (lathosterol, zymosterol and desmosterol) was detected. The enzymes cholesterol 24-hydroxylase and delta(24)-sterol reductase were also significantly decreased in HD putamen as compared with control tissues. Free radical-generated cholesterol oxidation products 7-keto cholesterol and 7β-hydroxycholesterol were also increased by 50-70% in HD putamen.
Conclusion: Human HD brain has significantly decreased cholesterol metabolism and disrupted cholesterol homeostasis. Our data also indicate that lipid oxidative stress accompanies HD pathology.
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http://dx.doi.org/10.1111/nan.12286 | DOI Listing |
Nutr Metab Cardiovasc Dis
December 2024
Department of Geriatrics Cardiology, The Second Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an, Shaanxi, 710004, China. Electronic address:
Background And Aim: The Naples Prognostic Score (NPS) predicts outcomes in various diseases, but its impact on cardiovascular disease (CVD) is understudied. This study investigates the association between NPS and CVD prevalence and mortality among US adults.
Methods And Results: This study utilized data from the Continuous National Health and Nutrition Examination Survey (NHANES) conducted between 1999 and 2016, with mortality follow-up data available through December 31, 2019.
Urology
January 2025
State University of Feira de Santana, Bahia, Brazil; Federal University of Ceará, Fortaleza, Ceará. Electronic address:
Background: The decline in testosterone levels among older men remains a subject of debate. While some cross-sectional and longitudinal studies have reported a decrease in testosterone with advancing age, others have not observed this trend. In this study, we aimed to evaluate testosterone levels and identify predictors of low testosterone in an age-stratified cohort of men.
View Article and Find Full Text PDFJ Nutr
January 2025
Nutrition and Food Security Research Center, Isfahan University of Medical Sciences, Isfahan, Iran. Electronic address:
Prediabetes with a considerable progression rate is a primary risk factor for type 2 diabetes, if left untreated. Dietary interventions examining the health effects of prebiotic consumption on health status have been studied in subjects with prediabetes but the results are controversial. This study aimed to investigate whether prebiotic consumption can favorably alter metabolic status as well as anthropometric features in subjects with prediabetes.
View Article and Find Full Text PDFReprod Toxicol
January 2025
Department of Morphology, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, MG, Brazil. Electronic address:
Saturated fat has been linked to cardiovascular diseases, leading to an increase in polyunsaturated fat consumption. The aim of the present study was to investigate the effects of three fat sources (coconut oil, lard and soybean oil) on metabolic and reproductive parameters in heterogenic mice. Female Swiss mice (5-6 weeks old; n=9/group) were divided into four experimental groups: control (CC), coconut oil (CO), lard (LA), and soybean oil (SO), and were orally given 0.
View Article and Find Full Text PDFDiabetes Res Clin Pract
January 2025
Diabetes Research Centre, College of Life Sciences, University of Leicester, Leicester General Hospital, Leicester LE5 4PW UK; NIHR Leicester Biomedical Research Centre, University Hospitals of Leicester NHS Trust and University of Leicester, Leicester LE5 4PW UK; Leicester Real World Evidence Unit, Leicester Diabetes Centre, University of Leicester, Leicester General Hospital, Leicester LE5 4PW UK.
Aims: Do associations between age at diagnosis of type 2 diabetes and vascular risk factors vary by ethnicity and deprivation?
Methods: Utilising the Clinical Practice Research Datalink, we matched 16-50-year-old individuals with newly diagnosed type 2 diabetes to ∼10 individuals without using sex, age and primary care practice. Differences in BMI, obesity, LDL-cholesterol, HbA1c, and hypertension between individuals with vs without type 2 diabetes across sex, age, ethnicity and deprivation quintiles were explored using generalised linear models.
Results: We included 108,061 individuals (45.
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