They are also used in treating hyperlipidaemia in atherosclerosis. Here they act by increasing the expression of ABCA1, which transports extra-hepatic cholesterol into HDL. Increased uptake and excretion from the liver therefore follows.
Animal studies have shown their possible role in amelioration of pulmonary inflammation, especially in asthma.
PPARδ (delta) is the main target of a research chemical named GW501516. It has been shown that agonism of PPARδ changes the body's fuel preference from glucose to lipids.
Dual and pan PPAR agonists
A fourth class of dual PPAR agonists, so-called glitazars, which bind to both the α and γ PPAR isoforms, are currently under active investigation for treatment of a larger subset of the symptoms of the metabolic syndrome. These include the experimental compounds aleglitazar, muraglitazar and tesaglitazar. In June 2013, saroglitazar was the first glitazar to be approved for clinical use.
In addition, there is continuing research and development of new dual α/δ and γ/δ PPAR agonists for additional therapeutic indications, as well as "pan" agonists acting on all three isoforms.
Both TLR4-mediated and NF-κB-mediated signalling pathways have been implicated in the development of addiction to several drugs such as opioids and cocaine, and therefore are appealing targets for pharmacotherapy.
Research suggests agonism of peroxisome proliferator-activated receptor alpha and peroxisome proliferator-activated receptor gamma receptors is capable of downregulating the activity of TLR4-mediated and NF-κB-mediated signalling pathways.
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