Intestine is the gateway for newly absorbed tocopherols. This organ also plays a crucial role in cholesterol metabolism. Because tocopherols are known to impact cholesterol metabolism in the liver, we hypothesized that tocopherols could also modulate cholesterol metabolism in the intestine. This study aimed to verify this hypothesis and to unveil the mechanisms involved, using Caco-2 cells as a model of the human intestinal cell. Both α- and γ-tocopherol significantly (P<.05) decreased endogenous cholesterol synthesis and apo-AI-mediated cholesterol secretion in Caco-2 cells. Tocopherols down-regulated (P<.05) up to half of the genes involved in the cholesterol synthesis pathway, together with CYP27A1, which is involved in oxysterol production. The activity of this enzyme, as well as the levels of intracellular oxysterols, was significantly diminished by tocopherols. Finally, tocopherols significantly reduced ABCA1 mRNA levels in Caco-2 cells. We conclude that tocopherols impair the endogenous synthesis and apo-AI-mediated secretion of cholesterol in Caco-2 cells. This effect involves a down-regulation of genes involved in the cholesterol synthesis pathway, resulting in down-regulation of CYP27A1 which, in turn, diminishes oxysterol concentrations. The outcome is a decrease of LXR activity, resulting in down-regulation of ABCA1. These data reinforce the effect of α- and γ-tocopherol on cholesterol metabolism via gene expression regulation.
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http://dx.doi.org/10.1016/j.jnutbio.2009.10.008 | DOI Listing |
Geroscience
January 2025
Center for Aging and Population Health, School of Public Health, University of Pittsburgh, 310 BelPB, 130 N. Bellefield Avenue, Pittsburgh, PA, 15213, USA.
Unintentional weight loss in older populations is linked to greater mortality and morbidity risks. This study aims to understand the metabolic mechanisms of unintentional weight loss and their relationship with body composition changes in older adults. We investigated plasma metabolite associations with weight and body composition changes over 5 years in 1335 participants (mean age 73.
View Article and Find Full Text PDFBackground: Cardiovascular-kidney-metabolic (CKM) health, a term recently defined by the American Heart Association, encompasses the interplay among metabolic, chronic kidney, and cardiovascular risk factors. We aimed to investigate the predictive significance of CKM disorders with the risk of cognitive decline and Alzheimer's disease (AD) and AD-related dementia (ADRD) mortality in a multiethnic population.
Method: We analyzed a cohort of 6,440 adults aged 45-84 who participated in the Multiethnic Study of Atherosclerosis, with a baseline survey conducted in 2000-2002, and were followed through to December 2015.
Background: Metabolic diseases like chronic Type 2 Diabetes Mellitus (T2DM) are now a serious global health concern In the United States. African Americans (AA) are being affected at a disproportionate rate with the condition compared to other ethnic groups, yet there are relatively few studies that have specifically focused on this group. Our previous findings have suggested that AA patients with T2DM had gene expression signals associated with Alzheimer's Disease (AD).
View Article and Find Full Text PDFBackground: Alzheimer's disease (AD) is thought to result from a complex cascade of events involving several pathological processes. Recent studies have reported alterations in white matter (WM) microstructure in the early phase of AD, but WM remains understudied. We used a multivariate approach to capture the complexity and heterogeneity of WM pathologies and its links to cognition and AD risk factors in a more holistic manner.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
Division of clinical Geriatrics, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet and Stockholm University, Stockholm, Sweden.
Background: The Cardiovascular risk factors, aging, and dementia (CAIDE) risk score is a validated tool estimating dementia risk. We investigated the association of CAIDE score with 12 markers of glucose and lipid metabolism, in the Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) participants.
Methods: The FINGER trial had 1260 participants, aged 60-77 years, with a CAIDE score ≥6, without substantial cognitive impairment.
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