Tissue Distribution and Versatile Functions of PPARs
Although PPAR subtypes share common features in terms of tissue distribution and ligand specificity, each subtype maintains a degree of individuality which enables it to perform subtype-specific functions. It has been established that PPARα, which is main
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Tissue Distribution and Versatile Functions of PPARs
Although PPAR subtypes share common features in terms of tissue distribution and ligand specificity, each subtype maintains a degree of individuality which enables it to perform subtype-specific functions. It has been established that PPARα, which is mainly expressed in the liver, heart, muscle, and kidney, augments fatty acid catabolism and acts as the molecular target for the lipid-lowering fibrate drugs. PPARβ/δ, in contrast, is ubiquitously expressed and is involved in the regulation of a variety of processes including keratinocyte differentiation, wound healing, inflammation, as well as glucose and lipid utilization. Finally, PPARγ is highly expressed in adipocytes and macrophages and is essential for adipocyte differentiation, lipid storage, and regulation of inflammation. PPARγ also mediates the activity of the insulin-sensitizing drugs thiazolidinediones and regulates glucose metabolism. Ongoing research continues to uncover roles for PPARs in a variety of biological pathways associated with normal processes and disease conditions. The following is a presentation of newly discovered, distinct functions of each PPAR subtype in different organs, including the advancement of rational basis for emerging controversial findings.
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Neurological Functions of PPARs
PPARs are expressed in several cell types in the brain including microglia, astrocytes, oligodendrocytes, and neurons (Heneka and Landreth 2007). PPAR ligands have proven useful in animal models of multiple sclerosis, Alzheimer’s and Parkinson’s diseases, as well as in trauma/stroke, suggesting a potential value in the treatment of these debilitating neuro-inflammatory diseases in humans (Bordet et al. 2006).
J.A. Youssef and M.Z. Badr, Peroxisome Proliferator-Activated Receptors: Discovery and Recent Advances, DOI 10.1007/978-1-62703-420-3_5, © Springer Science+Business Media New York 2013
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Tissue Distribution and Versatile Functions of PPARs
PPARα
PPARα mediates neuroprotective effects in brain injury. These effects are evidenced by an increase in PPARα protein expression and ligand-binding capacity in injured human brain (Feng et al. 2008). In addition, fenofibrate, a PPARα agonist, exerts a neuroprotective role in traumatic brain injury (Besson et al. 2005). PPARα agonists prevent proinflammatory responses of the microglia following exposure to radiation (Ramanan et al. 2008). Interestingly, it has also been suggested that neuroprotective effects of cannabinoids may be mediated through activation of PPARα (Sun et al. 2007). Additionally, PPARα is reported to play an important role in several other functions controlled by the central nervous system. Studies have revealed that PPARα is involved in sleep homeostasis. Bezafibrate, a PPARα agonist, was found to lower body temperature, enhance deep sleep, and improve resistance to sleep loss in mice (Chikahisa et al. 2008). Thus, PPARα may present a potential valuable target for the development of drugs to treat sleep disorders. Ot
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