Identification of a Novel Selective Peroxisome Proliferator-Activated Receptor α Agonist, 2-Methyl-2-(4-{3-[1-(4-methylbenzyl)-5-oxo-4,5-dihydro-1H-1,2,4-triazol-3-yl]propyl}phenoxy)propanoic Acid (LY518674), That Produces Marked Changes in Serum Lipids and Apolipoprotein A-1 Expression

2005 ◽  
Vol 68 (3) ◽  
pp. 763-768 ◽  
Author(s):  
Jai Pal Singh ◽  
Raymond Kauffman ◽  
William Bensch ◽  
Guoming Wang ◽  
Pam McClelland ◽  
...  
Keyword(s):  
Serum Lipids ◽  
Propanoic Acid ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Apolipoprotein A

scholarly journals Curcumin promotes AApoAII amyloidosis and peroxisome proliferation in mice by activating the PPARα signaling pathway

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Jian Dai ◽  
Ying Li ◽  
Fuyuki Kametani ◽  
Xiaoran Cui ◽  
Yuichi Igarashi ◽  
...  
Keyword(s):  
Density Lipoprotein ◽  
Amyloid Deposition ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferation ◽  
Hepatic Lipid Metabolism ◽  
Peroxisome Proliferator Activated Receptor ◽  
Apolipoprotein A ◽  
Affect Expression ◽  
Complex Manner ◽  
Ppar Pathway

Curcumin is a polyphenol compound that exhibits multiple physiological activities. To elucidate the mechanisms by which curcumin affects systemic amyloidosis, we investigated amyloid deposition and molecular changes in a mouse model of amyloid apolipoprotein A-II (AApoAII) amyloidosis, in which mice were fed a curcumin-supplemented diet. Curcumin supplementation for 12 weeks significantly increased AApoAII amyloid deposition relative to controls, especially in the liver and spleen. Liver weights and plasma ApoA-II and high-density lipoprotein concentrations were significantly elevated in curcumin-supplemented groups. RNA-sequence analysis revealed that curcumin intake affected hepatic lipid metabolism via the peroxisome proliferator-activated receptor (PPAR) pathway, especially PPARα activation, resulting in increased Apoa2 mRNA expression. The increase in liver weights was due to activation of PPARα and peroxisome proliferation. Taken together, these results demonstrate that curcumin is a PPARα activator and may affect expression levels of proteins involved in amyloid deposition to influence amyloidosis and metabolism in a complex manner.

scholarly journals Interaction of oestrogen and peroxisome proliferator-activated receptors with apolipoprotein(a) gene enhancers

2002 ◽  
Vol 366 (1) ◽  
pp. 157-163 ◽  
Author(s):  
Loretto H. PUCKEY ◽  
Brian L. KNIGHT
Keyword(s):  
Oestrogen Receptor ◽  
Hormone Receptors ◽  
Nuclear Hormone Receptor ◽  
Receptor Protein ◽  
Peroxisome Proliferator ◽  
Mobility Shift ◽  
Peroxisome Proliferator Activated Receptor ◽  
Apolipoprotein A ◽  
Increased Risk

A high plasma concentration of lipoprotein(a) [Lp(a)] confers an increased risk for the development of coronary heart disease. Hormones, such as oestrogen, are some of the few compounds known to reduce plasma Lp(a) levels. A putative enhancer region, located at the DHII DNase I hypersensitive site approx. 28kb upstream of the apolipoprotein(a) [apo(a)] gene, contains a number of sequences similar to the binding half-sites for nuclear hormone receptors, such as the oestrogen receptor and the peroxisome proliferator-activated receptor (PPAR). The 180bp core DHII enhancer increased the activity of the apo(a) promoter by over 7-fold in reporter-gene assays in HepG2 cells in vitro. Almost 60% of this increase was lost in the presence of co-transfected oestrogen receptor and oestrogen. In contrast, co-transfection with PPARα increased the effect of the DHII enhancer on apo(a) transcriptional activity by approx. 70% and could overcome the inhibitory effect of the oestrogen receptor on apo(a) transcription. Gel mobility-shift assays showed that oestrogen receptor protein bound to one half of a sequence corresponding to a predicted oestrogen receptor response element. PPARα also bound to this site and competed with oestrogen receptors for binding. In addition, PPARα bound to a separate site that comprised part of a direct repeat of nuclear hormone receptor half-sites. The results suggest that nuclear hormones affect plasma Lp(a) concentrations by binding to the sequences within the DHII enhancer, thereby altering the amount by which the enhancer increases the transcription of the apo(a) gene.

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