Background: Cholesterol homeostasis disorders may cause dyslipidemia, atherosclerosis progression and coronary artery disease (CAD) development. Evaluation of non-cholesterol sterols (NCSs) as synthesis and absorption markers, and lipoprotein particles quality may indicate the dyslipidemia early development. This study investigates associations of different cholesterol homeostasis patterns with low-density (LDL) and high-density lipoproteins (HDL) subclasses distribution in statin-treated and statin-untreated CAD patients, and potential use of aforementioned markers for CAD treatment optimization.
Methods: The study included 78 CAD patients (47 statin-untreated and 31 statin-treated) and 31 controls (CG). NCSs concentrations were quantified using gas chromatography- flame ionization detection (GC-FID). Lipoprotein subclasses were separated by gradient gel electrophoresis.
Results: In patients, cholesterol-synthesis markers were significantly higher comparing to CG. Cholesterol-synthesis markers were inversely associated with LDL size in all groups. For cholesterol homeostasis estimation, each group was divided to good and/or poor synthetizers and/or absorbers according to desmosterol and β-sitosterol median values. In CG, participants with reduced cholesterol absorption, the relative proportion of small, dense LDL was higher in those with increased cholesterol synthesis compared to those with reduced synthesis (p<0.01). LDL I fraction was significantly higher in poor synthetizers/poor absorbers subgroup compared to poor synthetizers/good absorbers (p<0.01), and good synthetizers/poor absorbers (p<0.01). Statin-treated patients with increased cholesterol absorption had increased proportion of LDL IVB (p<0.05).
Conclusions: The results suggest the existence of different lipoprotein abnormalities according to various patterns of cholesterol homeostasis. Desmosterol/β-sitosterol ratio could be used for estimating individual propensity toward dyslipidemia development and direct the future treatment.
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http://dx.doi.org/10.1515/cclm-2016-0505 | DOI Listing |
In p53-deficient cancers, targeting cholesterol metabolism has emerged as a promising therapeutic approach, given that p53 loss dysregulates sterol regulatory element-binding protein 2 (SREBP-2) pathways, thereby enhancing cholesterol biosynthesis. While cholesterol synthesis inhibitors such as statins have shown initial success, their efficacy is often compromised by the development of acquired resistance. Consequently, new strategies are being explored to disrupt cholesterol homeostasis more comprehensively by inhibiting its synthesis and intracellular transport.
View Article and Find Full Text PDFActa Physiol (Oxf)
February 2025
Laboratory of Biological Rhythms, Institute of Physiology of the Czech Academy of Sciences, Prague, Czech Republic.
Aim: Exposure to light at night and meal time misaligned with the light/dark (LD) cycle-typical features of daily life in modern 24/7 society-are associated with negative effects on health. To understand the mechanism, we developed a novel protocol of complex chronodisruption (CD) in which we exposed female rats to four weekly cycles consisting of 5-day intervals of constant light and 2-day intervals of food access restricted to the light phase of the 12:12 LD cycle.
Methods: We examined the effects of CD on behavior, estrous cycle, sleep patterns, glucose homeostasis and profiles of clock- and metabolism-related gene expression (using RT qPCR) and liver metabolome and lipidome (using untargeted metabolomic and lipidomic profiling).
Clin Nutr ESPEN
January 2025
Centro de Investigação de Montanha (CIMO), Instituto Politécnico de Bragança, Campus de Santa Apolónia, 5300-253 Bragança, Portugal; Laboratório Associado para a Sustentabilidade e Tecnologia em Regiões de Montanha (SusTEC), Instituto Politécnico de Bragança, Campus de Santa Apolónia, 5300-253 Bragança, Portugal. Electronic address:
Background: Dyslipidaemia is among the major causes of severe diseases and, despite being well-established, the hypocholesterolaemic therapies still face significant concerns about potential side effects (such as myopathy, myalgia, liver injury digestive problems, or mental fuzziness in some people taking statins), interaction with other drugs or specific foods. Accordingly, this review describes the latest developments in the most effective therapies to control and regulate dyslipidaemia.
Scope And Approach: Herein, the metabolic dynamics of cholesterol and their integration with the current therapies: statins, bile acid sequestrants, fibrates, niacin, proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, reconstituted high-density lipoprotein (rHDL), or anti-inflammatory and immune-modulating therapies), were compared focusing their effectiveness, patients' adhesion and typical side-effects.
Poult Sci
December 2024
College of Animal Science and Technology, Henan Agricultural University, Zhengzhou 450046, China; Key Laboratory of Livestock and Poultry Resources (Poultry) Evaluation and Utilization, Ministry of Agriculture and Rural Affairs, Zhengzhou 450046, China. Electronic address:
Fasting is beneficial to alleviate fatty liver, lose weight and improve reproductive function. However, previous studies have shown that, during fasting, disorders of bile acid metabolism were strongly associated with intestinal inflammation. The physiological and biochemical parameters and gene expression of multiple tissues of chickens at every critical time node were measured by ELISA and qPCR.
View Article and Find Full Text PDFCurr Atheroscler Rep
January 2025
Nantes Université, CHU Nantes, CNRS, Inserm, l'institut du thorax, F-44000, Nantes, France.
Purpose Of Review: While lipid-lowering therapies demonstrate efficacy, many patients still contend with significant residual risk of atherosclerotic cardiovascular diseases (ASCVD). The intestine plays a pivotal role in regulating circulating lipoproteins levels, thereby exerting influence on ASCVD pathogenesis. This review underscores recent genetic findings from the last six years that delineate new biological pathways and actors in the intestine which regulate lipid-related ASCVD risk.
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