The role of leptin in the pathomechanism of atherosclerosis, through its free radical generating ability is established. Its effect however, on the regulation of intracellular cholesterol synthesis has not been studied. The aim of the present study was to elucidate whether leptin influences endogenous cholesterol synthesis in monocytes. Furthermore, leptin signaling to HMG CoA reductase in control and hypercholesterolemic monocytes were compared. The in vitro effect of leptin was studied on freshly isolated human monocytes obtained from healthy control volunteers and patients with hypercholesterolemia. Our results can be summarized as follows: (1) Leptin is able to increase endogenous cholesterol synthesis in human monocytes in vitro. (2) The cholesterol synthesis increasing effect of the hormone is more pronounced in hypercholesterolemic monocytes with high basal cholesterol biosynthesis. (3) The leptin-induced Ca(2+) signal was involved in the enhancement of HMG CoA reductase activation in monocytes from both controls and hypercholesterolemic patients. (4) In control monocytes the Ca(2+) signal originated from intracellular pools, whereas in patients, Ca(2+)-influx and protein kinase C activation were found to be responsible for the leptin-effect. Mevalonate cycle inhibiting fluvastatin and 25-hydroxycholesterol decreased cholesterol production in leptin-stimulated monocytes. Our present study provides the first proof of the cholesterol synthesis enhancing effect of leptin through a statin-sensitive pathway in circulating monocytes. Furthermore our results suggest that leptin can be involved in the pathomechanism of atherosclerotic plaque formation also through its effect on cholesterol biosynthesis in monocytes.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.biocel.2007.04.012 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Chronic stress-induced cholesterol metabolism abnormalities promote ESCC tumorigenesis and predict neoadjuvant therapy response.
Proc Natl Acad Sci U S A
February 2025
Department of Pathophysiology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou 450000, China.
Recent studies have demonstrated that chronic stress can enhance the development of multiple human diseases, including cancer. However, the role of chronic stress in esophageal carcinogenesis and its underlying molecular mechanisms remain unclear. This study uncovered that dysregulated cholesterol metabolism significantly promotes esophageal carcinogenesis under chronic stress conditions.
View Article and Find Full Text PDFEffects of lipoic acid on production performance, meat quality, serum biochemistry and antioxidant function in heat-stressed broilers.
Trop Anim Health Prod
January 2025
College of Animal Sciences, Anhui Science and Technology University, Fengyang, 233100, China.
This study was aim to investigate the effects of lipoic acid (ALA) on performance, meat quality, serum biochemistry and antioxidant function of broilers under heat stress (HS). Two hundred1-day-old Cobb broilers were randomly divided into four treatment groups and each treatment consisted of 4 replicates of 10 broilers each. The treatment group adopts a 2 × 2 two-factor setting, which is divided into two diets (basic diet or 250 mg/kg ALA diet) and two temperatures (24 ± 1℃ or 33 ± 1℃).
View Article and Find Full Text PDFAdvances in understanding the role of squalene epoxidase in cancer prognosis and resistance.
Mol Biol Rep
January 2025
Department of Orthopedic Surgery, Institute of Bone Tumor, Shanghai Tenth People's Hospital Affiliated to Tongji University, Tongji University School of Medicine, Shanghai, 200092, China.
Recently, there has been burgeoning interest in the involvement of cholesterol metabolism in cancer. Squalene epoxidase (SQLE), as a critical rate-limiting enzyme in the cholesterol synthesis pathway, has garnered attention due to its overexpression in various cancer types, thereby significantly impacting tumor prognosis and resistance mechanisms. Firstly, SQLE contributes to unfavorable prognosis through diverse mechanisms, encompassing modulation of the PI3K/AKT signaling pathway, manipulation of the cancer microenvironment, and participation in ferroptosis.
View Article and Find Full Text PDFCholesterol-terminated cationic lipidated oligomers (CLOs) as a new class of antifungals.
J Mater Chem B
January 2025
Drug Delivery, Disposition, and Dynamics Theme, Monash Institute of Pharmaceutical Sciences, Monash University, 381 Royal Pde, Parkville, VIC, 3052, Australia.
Infections caused by fungal pathogens are a global health problem, and have created an urgent need for new antimicrobial strategies. This report details the synthesis of lipidated 2-vinyl-4,4-dimethyl-5-oxazolone (VDM) oligomers an optimized Cu(0)-mediated reversible-deactivation radical polymerization (RDRP) approach. Cholesterol-Br was used as an initiator to synthesize a library of oligo-VDM (degree of polymerisation = 5, 10, 15, 20, and 25), with an α-terminal cholesterol group.
View Article and Find Full Text PDFRing A Cleaving Beta-Diketone Hydrolase Is a Key Enzyme of Steroid Degradation in Anaerobic Bacteria.
Environ Microbiol
January 2025
Faculty of Biology-Microbiology, University of Freiburg, Freiburg, Germany.
Bacterial degradation of ubiquitous and persistent steroids such as steroid hormones is important for their removal from the environment. Initial studies of steroid degradation in anaerobic bacteria suggested that ring-cleaving hydrolases are involved in oxygen-independent sterane skeleton degradation. However, the enzymes involved in ring A cleavage of the common intermediate androsta-1,4-diene-3,17-dione have remained unknown.
View Article and Find Full Text PDFWant 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!