Cryptochrome and Period Proteins Are Regulated by the CLOCK/BMAL1 Gene: Crosstalk between the PPARs/RXRalpha-Regulated and CLOCK/BMAL1-Regulated Systems.

Feeding and the circadian system regulate lipid absorption and metabolism, and the expression of enzymes involved in lipid metabolism is believed to be directly controlled by the clock system. To investigate the interaction between the lipid metabolism system and the circadian system, we analyzed the effect of a CLOCK/BMAL1 heterodimer on the transcriptional regulation of PPAR-controlled genes through PPAR response elements (PPREs). Transcription of acyl-CoA oxidase, cellular retinol binding protein II (CRBPII), and 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) synthase was altered by CLOCK/BMAL1, and transcriptional activity via PPRE by PPARs/RXRalpha was enhanced by CLOCK/BMAL1 and/or by PPARs ligand/activators.

Disruption of the murine intestinal alkaline phosphatase gene Akp3 impairs lipid transcytosis and induces visceral fat accumulation and hepatic steatosis.

Intestinal alkaline phosphatase (IAP) is involved in the process of fat absorption, a conclusion confirmed by an altered lipid transport and a faster body weight gain from 10 to 30 wk in both male and female mice with a homozygous null mutation of the IAP coding gene (Akp3(-/-) mice). This study was aimed to delineate morphologically and quantitatively the accelerated lipid absorption in male Akp3(-/-) mice. Feeding a corn oil bolus produced an earlier peak of triacylglycerol in serum (2 vs.

Apoptosis of endothelial cells may be mediated by genes of peroxisome proliferator-activated receptor gamma 1 (PPARgamma 1) and PPARalpha genes.

Apoptosis in human umbilical vein endothelial cells (HUVECs) was prevented by transfection with the gene for the human full-length peroxisome proliferator-activated receptor alpha (PPARalpha), or acyl-coenzyme A synthetase (AcylCS) into HUVECs. In contrast, ligands/activators of PPARgamma 1 induced apoptosis by a cytochrome c-dependent mechanism in HUVECs transfected with human full-length PPARgamma 1, but not in hepatocytes. Co-transfection of PPARgamma 1 and PPARalpha protected the HUVEC apoptosis.