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Diabetologia
Published in: Diabetologia 1/2007

01-01-2007 | Review

Peroxisome proliferator-activated receptor-δ, a regulator of oxidative capacity, fuel switching and cholesterol transport

Authors: C. Fürnsinn, T. M. Willson, B. Brunmair

Published in: Diabetologia | Issue 1/2007

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Abstract

Synthetic agonists of peroxisome proliferator-activated receptor (PPAR)-δ have shown a promising pharmacological profile in preclinical models of metabolic and cardiovascular disease. At present, the pharmaceutical development of these drugs exploits the potential to raise plasma HDL-cholesterol in animals and their insulin-sensitising and glucose-lowering properties. PPAR-δ agonists have also proven to be powerful research tools that have provided insights into the role of fatty acid metabolism in human physiology and disease. Activation of PPAR-δ induces the expression of genes important for cellular fatty acid combustion and an associated increase in whole-body lipid dissipation. The predominant target tissue in this regard is skeletal muscle, in which PPAR-δ activation regulates the oxidative capacity of the mitochondrial apparatus, switches fuel preference from glucose to fatty acids, and reduces triacylglycerol storage. These changes counter the characteristic derangements of insulin- resistant skeletal muscle but resemble the metabolic adaptation to regular physical exercise. Apart from effects on fuel turnover, there is evidence for direct antiatherogenic properties, because PPAR-δ activation increases cholesterol export and represses inflammatory gene expression in macrophages and atherosclerotic lesions. Whereas conclusions about the full potential of PPAR-δ as a drug target await the result of large scale clinical testing, ongoing investigation of this nuclear receptor has greatly improved our knowledge of the physiological regulation of whole-body fuel turnover and the interdependence of mitochondrial function and insulin sensitivity.
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Metadata
Title
Peroxisome proliferator-activated receptor-δ, a regulator of oxidative capacity, fuel switching and cholesterol transport
Authors
C. Fürnsinn
T. M. Willson
B. Brunmair
Publication date
01-01-2007
Publisher
Springer-Verlag
Published in
Diabetologia / Issue 1/2007
Print ISSN: 0012-186X
Electronic ISSN: 1432-0428
DOI
https://doi.org/10.1007/s00125-006-0492-0

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