Download or read book Circadian Integration of Hepatic de Novo Lipogenesis and Peripheral Energy Substrates Utilization written by Sihao Liu and published by . This book was released on 2012 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: The liver maintains energy substrate homeostasis by synchronizing circadian or diurnal expression of metabolic genes with the feeding/fasting state. The activities of hepatic de novo lipogenic gene products peak during feeding, converting carbohydrates into fats that provide vital energy sources for peripheral tissues. Conversely, deregulated hepatic lipid synthesis leads to systemic metabolic dysfunction, establishing the importance of temporal regulation of fat synthesis/usage in metabolic homeostasis. Pharmacological activation of peroxisome proliferator-activated receptor [delta]/[beta] (PPAR[delta]/[beta]) improves glucose handling and systemic insulin sensitivity. However, the mechanisms of hepatic PPAR[delta] actions and the molecular pathways through which it is able to modulate global metabolic homeostasis remain unclear. Here we show that hepatic PPAR[delta] controls the diurnal expression of lipogenic genes in the dark/feeding cycle. Adenovirus mediated liver restricted activation of PPAR[delta] promotes glucose utilization in the liver and fat utilization in the muscle. Liver specific deletion of either PPAR[delta] or the PPAR[delta]-regulated lipogenic gene acetyl-CoA carboxylase 1 (ACC1) reduces muscle fatty acid uptake. Unbiased metabolite profiling identifies 1-stearoyl-2-oleoyl-sn-glycero-3-phosphocholine (SOPC) as a serum lipid derived from the hepatic PPAR[delta]-ACC1 activity that reduces postprandial lipid levels and increases muscle fatty acid uptake. These findings reveal a regulatory mechanism that coordinates lipid synthesis and utilization in the liver-muscle axis, providing mechanistic insights into the hepatic regulation of systemic energy substrates homeostasis.