Peroxisome proliferator-activated receptors (PPARs) are transcription factors that play a critical role in regulating lipid and glucose metabolism, cell growth and cell differentiation. PPAR alpha is expressed in highly metabolically active tissues (alpha = active), including the PT and TALH in the kidney, where fatty acids are a major source of fuel. Activation of PPAR alpha causes genes involved in the control of fatty acid beta-oxidation to be expressed.
In mouse models of ischemia-reperfusion and nephrotoxic AKI, reduced PPAR alpha activity leads to reduced expression of fatty acid oxidative enzymes. This causes nephrotoxic long chain fatty acids such as 4-HHE to build up, causing cell toxicity and death. As such, PPAR alpha plays an essential nurturing role to nephrons during AKI.
In future, we may give PPAR alpha activators for the prevention of AKI in high risk patients. Indeed, the PPAR-activating fibrates are showing some early promise of fulfilling this role.