| Gene expression analyses in cynomolgus monkeys provides mechanistic insight into high-density lipoprotein-cholesterol reduction by androgens in primates. | |
| | |
MedLine Citation:
|
PMID: 18187556 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
Androgens increase muscle mass, decrease fat mass, and reduce high-density lipoprotein cholesterol (HDL), but the relationship between body composition, lipoprotein metabolism, and androgens has not been explained. Here we treated ovariectomized cynomolgus monkeys with 5alpha-dihydrotestosterone (DHT) or vehicle for 14 d and measured lipoprotein and triglycerides. Nuclear magnetic resonance analysis revealed that DHT dose-dependently reduced the cholesterol content of large HDL particles and decreased mean HDL particle size (P < 0.01) and also tended to lower low-density lipoprotein cholesterol without altering other lipoprotein particles. Liver and visceral fat biopsies taken before and after DHT treatment for 1 or 14 d were analyzed by genome-wide microarrays. In liver, DHT did not alter the expression of most genes involved in cholesterol synthesis or uptake but rapidly increased small heterodimer partner (SHP) RNA, along with concomitant repression of CYP7A1, a target of SHP transcriptional repression and the rate-limiting enzyme in bile acid synthesis. DHT regulation of SHP and CYP7A1 also occurs in rats, indicating a conserved mechanism. In adipose tissue, pathway analyses suggested coordinate regulation of adipogenesis, tissue remodeling, and lipid homeostasis. Genes encoding IGF-I and beta-catenin were induced, as were extracellular matrix, cell adhesion, and cytoskeletal components, whereas there was consistent down-regulation of genes involved in triacylglycerol metabolism. Interestingly, cholesterol ester transfer protein RNA was induced rapidly in monkey adipose tissue, whereas its inhibitor apolipoprotein CI was repressed. These data provide insight into the androgenic regulation of lipoprotein homeostasis and suggest that changes in adipose lipoprotein metabolism could contribute to HDL cholesterol reduction. |
| | |
Authors:
|
Pascale Nantermet; Shun-ichi Harada; Yuan Liu; Spring Cheng; Colena Johnson; Yuanjiang Yu; Donald Kimme; Daniel Holder; Paul Hodor; Robert Phillips; William J Ray |
Related Documents
:
|
7119576 - Diet-induced and physiologically occurring hypercholesterolemias in the spontaneous hyp... 678226 - A new large chylomicron remnant from cholesterol-fed rabbits. 22060306 - Use of electrical stimulation, hot processing and carrageenan for processing low-fat gr... 1974416 - Effect of alcohol intake on human apolipoprotein a-i-containing lipoprotein subfractions. 14077036 - Toxin-producing aspergillus isolated from domestic peanuts. 19064506 - Percentage extremity fat, but not percentage trunk fat, is lower in adolescent boys wit... |
Publication Detail:
|
Type: Journal Article Date: 2008-01-10 |
Journal Detail:
|
Title: Endocrinology Volume: 149 ISSN: 0013-7227 ISO Abbreviation: Endocrinology Publication Date: 2008 Apr |
Date Detail:
|
Created Date: 2008-03-24 Completed Date: 2008-05-06 Revised Date: 2009-04-16 |
Medline Journal Info:
|
Nlm Unique ID: 0375040 Medline TA: Endocrinology Country: United States |
Other Details:
|
Languages: eng Pagination: 1551-61 Citation Subset: AIM; IM |
Affiliation:
|
Department of Alzheimer's Disease Research, Merck Research Laboratories, West Point, PA 19486, USA. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Adipose Tissue
/
metabolism* Animals Body Composition Cholesterol 7-alpha-Hydroxylase / genetics, physiology Cholesterol Ester Transfer Proteins / genetics Cholesterol, HDL / blood* Cholesterol, LDL / blood Dihydrotestosterone / pharmacology* Dose-Response Relationship, Drug Female Liver / metabolism Macaca fascicularis Oligonucleotide Array Sequence Analysis Particle Size Rats Rats, Sprague-Dawley Receptors, Cytoplasmic and Nuclear / genetics |
| Chemical | |
Reg. No./Substance:
|
0/Cholesterol Ester Transfer Proteins; 0/Cholesterol, HDL; 0/Cholesterol, LDL; 0/Receptors, Cytoplasmic and Nuclear; 0/nuclear receptor subfamily 0, group B, member 2; 521-18-6/Dihydrotestosterone; EC 1.14.13.17/Cholesterol 7-alpha-Hydroxylase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Low doses of insulin-like growth factor I improve insulin resistance, lipid metabolism, and oxidativ...
Next Document: Genetic variants in peroxisome proliferator-activated receptor-gamma gene are associated with risk o...