Objective: Acyl-coenzyme A: cholesterol acyltransferase (ACAT) converts intracellular free cholesterol (FC) into cholesteryl esters (CE) for storage in lipid droplets. Recent studies in our laboratory have shown that the deletion of the macrophage ACAT1 gene results in apoptosis and increased atherosclerotic lesion area in the aortas of hyperlipidemic mice. The objective of the current study was to elucidate the mechanism of the increased atherosclerosis.
Methods And Results: CE storage and FC efflux were studied in ACAT1(-/-) peritoneal macrophages that were treated with acetylated low-density lipoprotein (acLDL). Our results show that efflux of cellular cholesterol was reduced by 25% in ACAT1-deficient cells compared with wild-type controls. This decrease occurred despite the upregulated expression of ABCA1, an important mediator of cholesterol efflux. In contrast, ACAT1 deficiency increased efflux of the cholesterol derived from acLDL by 32%. ACAT1-deficient macrophages also showed a 26% increase in the accumulation of FC derived from acLDL, which was associated with a 75% increase in the number of intracellular vesicles.
Conclusions: Together, these data show that macrophage ACAT1 influences the efflux of both cellular and lipoprotein-derived cholesterol and propose a pathway for the pro-atherogenic transformation of ACAT1(-/-) macrophages.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1161/01.ATV.0000148323.94021.e5 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
ACAT1/SOAT1 maintains adipogenic ability in preadipocytes by regulating cholesterol homeostasis.
J Lipid Res
December 2024
Department of Food Science and Nutrition, The Hong Kong Polytechnic University, Kowloon, Hung Hom, Hong Kong; Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Kowloon, Hung Hom, Hong Kong; Research Institute for Future Food, The Hong Kong Polytechnic University, Kowloon, Hung Hom, Hong Kong; The Hong Kong Polytechnic University Shenzhen Research Institute, The Hong Kong Polytechnic University, Shenzhen, China. Electronic address:
Maintaining cholesterol homeostasis is critical for preserving adipocyte function during the progression of obesity. Despite this, the regulatory role of cholesterol esterification in governing adipocyte expandability has been understudied. Acyl-coenzyme A (CoA):cholesterol acyltransferase/Sterol O-acyltransferase 1 (ACAT1/SOAT1) is the dominant enzyme to synthesize cholesteryl ester in most tissues.
View Article and Find Full Text PDFDichorionic diamniotic twin pregnancy after preimplantation genetic testing and single blastocyst transfer.
Birth Defects Res
June 2024
Laboratory of Basic Medicine, Fuzong Clinical College of Fujian Medical University (900th Hospital of the Joint Logistics Support Force), Fuzhou, China.
Background: In addition to the potential for multiple pregnancies, natural conception occurring in preimplantation genetic testing (PGT) increases undesired genetic risk. Some studies showed that a dichorionic diamniotic twin pregnancy after a single blastocyst transfer could be caused by embryo splitting or concurrent spontaneous conception.
Case: We describe a patient undergoing PGT who had a dichorionic diamniotic twin pregnancy after single blastocyst transfer in a natural cycle.
Diabetic ketoacidosis in an adult with beta-ketothiolase deficiency (BKD) involving a novel ACAT1 variant : first report of established diabetes in BKD and a review of the literature.
Clin Diabetes Endocrinol
June 2024
Department of Endocrinology, Royal Prince Alfred Hospital, Sydney, NSW, Australia.
Article Synopsis
- Diabetes in young adults can be difficult to classify, particularly when involving diabetic ketoacidosis (DKA) seen in both type 1 and type 2 diabetes, and can also be linked to rare conditions like Beta-ketothiolase deficiency (BKD).
- A novel case is presented of a 34-year-old man with BKD who experienced DKA, which is unique because previous reports haven't documented diabetes in adults with BKD.
- The findings stress the need for regular HbA1c checks in those with BKD and raised blood sugar levels to identify possible concurrent diabetes, which can help avoid complications and improve treatment strategies.
[Clinical analysis and genetic diagnosis of three children with Isoleucine metabolic disorders due to variants of HSD17B10 and ACAT1 genes].
Zhonghua Yi Xue Yi Chuan Xue Za Zhi
May 2024
Neonatal Screening Center, Shanghai Children's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200040, China.
Objective: To explore the clinical, biochemical and genetic characteristics of three children with Isoleucine metabolic disorders due to variants of HSD17B10 and ACAT1 genes.
Methods: Two children with 17β hydroxysteroid dehydrogenase 10 (HSD17B10) deficiency and a child with β-ketothiolase deficiency (BKD) diagnosed at Shanghai Children's Hospital between 2014 and 2021 were selected as the study subjects. Clinical data of the children were collected.
[Clinical features and genetic analysis of three children with β-ketothiolase deficiency].
Zhonghua Yi Xue Yi Chuan Xue Za Zhi
March 2024
Department of Endocrinology and Inborn Error of Genetic Metabolism, Children's Hospital Affiliated to Zhengzhou University, Henan Children's Hospital, Zhengzhou Children's Hospital, Zhengzhou, Henan 450053, China.
Objective: To explore the clinical features and genetic variants in three children suspected for β-ketothiolase deficiency (BKTD).
Methods: Clinical manifestations, laboratory examination and genetic testing of three children suspected for BKTD at Henan Children's Hospital between January 2018 and October 2022 were collected, and their clinical and genetic variants were retrospectively analyzed.
Results: The children were all males with a age from 7 to 11 months.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!