We would like to offer a different opinion on the ideas presented in the article by Keshava and Caldwell (2006). The authors indicated that their article summarized scientific literature published since an earlier U.S. Environmental Protection Agency (EPA) risk assessment of trichloroethylene (TCE), with an emphasis on the possible role of proliferator-activated receptor α (PPARα) agonism relev...

Peroxisome proliferator-activated receptor alpha (PPARα) is a member of the large nuclear receptor superfamily whose main role is to activate genes involved in fatty acid oxidation in the liver, heart, kidney and skeletal muscle. While currently used mainly as hypolipidemic agents, the cardiac effects and anti-inflammatory actions of PPARα agonists in arterial wall cells suggest other potential...

Peroxisome proliferator-activated receptor α is a member of the nuclear receptor superfamily. It modulates smooth muscle cell proliferation and inflammatory cytokines in vitro. In this study, we tested the hypothesis that PPARα would decrease the expression of monocyte chemoattractant protein-1 and tissue factor, and inhibit neointimal formation in a murine double carotid artery injury model. C...

Inhibitor of DNA binding (Id2) is a helix-loop-helix (HLH) transcription factor that participates in cell differentiation and proliferation. Id2 has been linked to the development of cardiovascular diseases since thiazolidinediones, antidiabetic agents and peroxisome proliferator-activated receptor (PPAR) gamma agonists, have been reported to diminish Id2 expression in human cells. We hypothesi...

Numerous clinical and population studies have demonstrated that increased serum bilirubin levels protect against cardiovascular and metabolic diseases such as obesity and diabetes. Bilirubin is a potent antioxidant, and the beneficial actions of moderate increases in plasma bilirubin have been thought to be due to the antioxidant effects of this bile pigment. In the present study, we found that...

Red meat consumption is associated with an increased colon cancer risk. Heme, present in red meat, injures the colon surface epithelium by luminal cytotoxicity and reactive oxygen species. This surface injury is overcompensated by hyperproliferation and hyperplasia of crypt cells. Transcriptome analysis of mucosa of heme-fed mice showed, besides stress- and proliferation-related genes, many upr...

Peroxisome proliferator-activated receptor-α (PPARα) mediates metabolic remodeling, resulting in enhanced mitochondrial and peroxisomal β-oxidation of fatty acids. In addition to the physiological stimuli of fasting and high-fat diet, PPARα is activated by the fibrate class of drugs for the treatment of dyslipidemia. Sirtuin 1 (SIRT1), an important regulator of energy homeostasis, was downregul...

Apart from impaired β-oxidation, Pparα-deficient (Pparα) mice suffer from hypoglycemia during prolonged fasting, suggesting alterations in hepatic glucose metabolism. We compared hepatic glucose metabolism in vivo in wild-type (WT) and Pparα mice after a short-term fast, applying novel isotopic methods. After a 9h fast mice were infused with [U-C] glucose, [2-C]glycerol, [1-H]galactose and para...