the contrasting roles of pparδ and pparγ in regulating the metabolic switch between oxidation and storage of fats in white adipose tissuepparδ截然不同的角色和pparγ在调节脂肪代谢氧化和存储之间切换的白色脂肪组织.pdf

Roberts et al. Genome Biology 2011, 12:R75 /2011/12/8/R75 RESEARCH Open Access The contrasting roles of PPARδ and PPARg in regulating the metabolic switch between oxidation and storage of fats in white adipose tissue 1,2 3 3 1 4 Lee D Roberts , Andrew J Murray , David Menassa , Tom Ashmore , Andrew W Nicholls and Julian L Griffin 1,2,5,6* Abstract Background: The nuclear receptors peroxisome proliferator-activated receptor g (PPARg) and peroxisome proliferator-activated receptor δ (PPARδ) play central roles in regulating metabolism in adipose tissue, as well as being targets for the treatment of insulin resistance. While the role of PPARg in regulating insulin sensitivity has been well defined, research into PPARδ has been limited until recently due to a scarcity of selective PPARδ agonists. Results: The metabolic effects of PPARg and PPARδ activation have been examined in vivo in white adipose tissue from ob/ob mice and in vitro in cultured 3T3-L1 adipocytes using 1H nuclear magnetic resonance spectroscopy and mass spectrometry metabolomics to understand the receptors’ contrasting roles. These steady state measurements were supplemented with 13C-stable isotope substrate labeling to assess fluxes, in addition to respirometry and transcriptomic microarray analysis. The metabolic effects of the receptors were readily distinguished, with PPARg activation characterized by increased fat storage, synthesis and elongation, while PPARδ activation caused increased fatty acid b-oxidation, tricarboxylic acid cycle rate and oxidation of extracellular branch chain amino acids. Stimulated glycolysis and increased fatty acid desaturation were common pathways for the agonists. Conclusions: