Three Members of the Human Pyruvate Dehydrogenase Kinase Gene Family Are Direct Targets of the Peroxisome Proliferator-activated Receptor β/δ

Lipolytic Products Activate Peroxisome Proliferator-activated Receptor (PPAR) α and δ in Brown Adipocytes to Match Fatty Acid Oxidation with Supply

“…Lipolytic products are detected by PPAR␣ and PPAR␦, which are both critical regulators of the thermogenic program in BAT (16,29). In agreement, both PPAR␣ (16,26) and PPAR␦ (29 -31) bind the UCP1 and PDK4 (27,32) promoters. Interestingly, the PGC1␣ PPAR response element is responsive to PPAR␣ but not PPAR␦ (33); this is in agreement with our antagonist and siRNA studies in which only PPAR␣ modulation affected PGC1␣ expression.…”

“…The promoter elements of PGC1␣ (26), PDK4 (27), and UCP1 (28) contain PPAR response elements and likely define the means by which lipolysis regulates their expression. Lipolytic products are detected by PPAR␣ and PPAR␦, which are both critical regulators of the thermogenic program in BAT (16,29).…”

Genetic dissection of retinoid esterification and accumulation in the liver and adipose tissue

“…As shown in Fig. 6C , we observed a marked downregulation in expression of the key regulatory enzyme Pdk4 , which is a known target gene for Ppar ␦ transcriptional regulation ( 47 ).…”

“…We did not detect signifi cant differences between matched mutant and WT mice in hepatic expression of regulatory genes commonly associated with hepatic steatosis, specifi cally Ppar ␣ and Ppar ␥ . Strikingly though, Ppar ␦ mRNA levels were downregulated by more than 75% and levels of the Ppar ␦ target gene Pdk4 ( 47 ) were similarly downregulated in the livers of CrbpI…”

The oncogene c-Myc coordinates regulation of metabolic networks to enable rapid cell cycle entry

“…The paradoxical increase in PDK1, recently shown to be activated by Myc, 28 is confounding. However, recent work indicates that PDK2 and PDK4 are regulated by the PPARs, 35 and the temporal reduction in expression of PPARGC1a on induction of Myc (Suppl . Table S1), may lead to a concomitant drop in PDK2 and 4.…”