Peroxisome proliferator activated receptor α (PPARα) stimulates hepatocellular proliferation is species-specific. Activation of mouse, but not human, PPARα induces hepatocellular proliferation, hepatomegaly, and liver cancer. Here we tested the hypothesis that human and mouse PPARα affects liver regeneration differentially. PPARα-humanized mice (hPPARα(PAC)) were similar to wild type mice in re...

Peroxisome proliferator-activated receptor-α (PPARα) regulates hepatic fatty acid catabolism and mediates the metabolic response to starvation. Recently we found that PPARα is constitutively activated in nuclei of hippocampal neurons and controls plasticity via direct transcriptional activation of CREB. Here we report the discovery of three endogenous PPARα ligands-3-hydroxy-(2,2)-dimethyl buty...

Peroxisome proliferator-activated receptor α (PPARα) is a member of the nuclear/steroid receptor gene superfamily that also comprises β, δ, and γ isoforms. PPARα is a ligand-activated transcription factor that plays an important role in the regulation of many genes involved in key metabolic processes. Today, PPARα has been cloned from mammalian, marsupial, and a number of marine species and its...

The N-acylethanolamines (NAEs), oleoylethanolamide (OEA) and palmithylethanolamide (PEA) are known to be endogenous ligands of PPARα receptors, and their presence requires the activation of a specific phospholipase D (NAPE-PLD) associated with intracellular Ca(2+) fluxes. Thus, the identification of a specific population of NAPE-PLD/PPARα-containing neurons that express selective Ca(2+)-binding...

Objective: The angiotensin type 1 receptor blocker (ARB) and PPARγ-modulator telmisartan has been recently demonstrated to reduce plasma triglycerides in non-diabetic and diabetic hypertensive patients. The present study investigates the molecular mechanisms of telmisartans hypolipidemic actions, in particular its effect on the PPARα pathway. Research Design and Methods: Regulation of PPARα-tar...

Fatty acid oxidation and subsequent ketogenesis is one of the major mechanisms to maintain hepatic lipid homeostasis under fasting conditions. Fasting hormone glucagon has been shown to stimulate ketone body production through activation of PPARα; however, the signal pathway linking glucagon to PPARα is largely undiscovered. Here we report that a SIK2-p300-PPARα cascade mediates glucagon's effe...

2,4-dinitrotoluene (2,4-DNT) is a nitroaromatic used in industrial dyes and explosives manufacturing processes that is found as a contaminant in the environment. Previous studies have implicated antagonism of PPARα signaling as a principal process affected by 2,4-DNT. Here, we test the hypothesis that 2,4-DNT-induced perturbations in PPARα signaling and resultant downstream deficits in energy m...

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...