Diabetes Metab J.  2011 Aug;35(4):327-336. 10.4093/dmj.2011.35.4.327.

Role of Peroxisome Proliferator-Activated Receptor alpha in Diabetic Nephropathy

• Chung S
• Park CW

• KMID: 2281638
• DOI: http://doi.org/10.4093/dmj.2011.35.4.327

Abstract

With a developing worldwide epidemic of diabetes mellitus, the renal complications associated with diabetes have become a serious health concern. Primary therapy for treating diabetic nephropathy is a multifactorial process. Peroxisome proliferator-activated receptor alpha (PPARalpha) agonists have been used primarily in clinical practice for the treatment of dyslipidemia and insulin resistance. Given that PPARalpha expression and regulation of metabolic pathways are involved in oxidative stress, inflammation, blood pressure regulation, and the renin-angiotensin aldosterone system, PPARalpha likely influences the development and pathogenesis of diabetic nephropathy via indirect effects on glucose and lipid homeostasis and also by direct action on the kidneys. These findings suggest that PPARalpha may become an important therapeutic target for treating diabetic renal complications.

Keyword

Diabetes mellitus; Kidney; PPAR alpha

MeSH Terms

Aldosterone
Blood Pressure
Diabetes Mellitus
Diabetic Nephropathies
Dyslipidemias
Glucose
Homeostasis
Inflammation
Insulin Resistance
Kidney
Metabolic Networks and Pathways
Oxidative Stress
Peroxisomes
PPAR alpha
Aldosterone
Glucose
PPAR alpha

Figure

• 

  Fig. 1 Structure and molecular mechanism of action of peroxisome proliferator-activated receptor alpha (PPARα). (A) PPARα has four functional domains: the N-terminal ligand-independent transactivation domain (A/B domain); DNA binding domain (DBD or C domain), including an activation function-1 (AF-1); co-factor docking domain (D domain); and C-terminal E/F domain including a ligand binding domain (LBD) and an activation function-2 (AF-2). (B) The PPARα and retinoid X receptor-α (RXRα) heterodimer, which can recruit diverse coactivators and corepressors that modulate the transcriptional activity of PPARα, binds to PPAR-response elements (PPRE) to activate target gene transcription.

• 

  Fig. 2 Protective actions of peroxisome proliferator-activated receptor alpha (PPARα) agonists for the improvement of diabetic nephropathy. In diabetic patients, symptoms such as hyperglycemia, dyslipidemia, endothelial dysfunction, lipotoxicity, and high blood pressure all can contribute to renal complications of diabetes systemically or locally via increased inflammation, activation of the renin-angiotensin system (RAS), enhanced oxidative stress, increased apoptosis and vasculopathy, which can be attenuated by the activation of PPARα. TGF, transforming growth factor; VEGF, vascular endothelial growth factor.

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