English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools annual

Global: Zendy Free Plan

Global: Zendy Tools monthly

Global: Zendy Plus monthly

Thiazolidinediones are antidiabetic agents, which not only improve glucose metabolism but also reduce blood triglyceride concentrations. These compounds are synthetic ligands for PPARγ, a transcription factor belonging to the nuclear receptor subfamily of PPARs, which are important transcriptional regulators of lipid and lipoprotein metabolism. The goal of this study was to evaluate the influence of a potent thiazolidinedione,BRL49653 , on serum lipoproteins and to determine whether its lipid-lowering effects are mediated by changes in the expression of key genes implicated in lipoprotein metabolism. Treatment of normal rats for 7 days withBRL49653 decreased serum triglycerides in a dose-dependent fashion without affecting serum total and HDL cholesterol and apolipoprotein (apo) A-I and apo A-II concentrations. The decrease in triglyceride concentrations afterBRL49653 was mainly due to a reduction of the amount of VLDL particles of unchanged lipid and apo composition.BRL49653 treatment did not change triglyceride production in vivo as analyzed by injection of Triton WR-1339, indicating a primary action on triglyceride catabolism. Analysis of the influence ofBRL49653 on the expression of LPL and apo C-III, two key players in triglyceride catabolism, showed a dose-dependent increase in mRNA levels and activity of LPL in epididymal adipose tissue, whereas liver apo C-III mRNA levels remained constant. Furthermore, addition ofBRL49653 to primary cultures of differentiated adipocytes increased LPL mRNA levels, indicating a direct action of the drug on the adipocyte. Simultaneous administration ofBRL49653 and fenofibrate, a hypolipidemic drug that acts primarily on liver through activation of PPARα both decreased liver apo C-III and increased adipose tissue LPL mRNA levels, resulting in a more pronounced lowering of serum triglycerides than each drug alone. In conclusion, both fibrates and thiazolidinediones exert a hypotriglyceridemic effect. While fibrates act primarily on the liver by decreasing apo C-III production,BRL49653 acts primarily on adipose tissue by increasing lipolysis through the induction of LPL expression. Drugs combining both PPARα and γ activation potential should therefore display a more efficient hypotriglyceridemic activity than either compound alone and may provide a rationale for improved therapy for elevated triglycerides.

Regulation of Lipoprotein Metabolism by Thiazolidinediones Occurs through a Distinct but Complementary Mechanism Relative to Fibrates