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Mol Metab. 2014 Mar 6;3(4):354-71. doi: 10.1016/j.molmet.2014.02.002. eCollection 2014 Jul.

Integrated physiology and systems biology of PPARα.

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1
Nutrition, Metabolism and Genomics Group, Wageningen University, Bomenweg 2, 6703HD Wageningen, The Netherlands.

Abstract

The Peroxisome Proliferator Activated Receptor alpha (PPARα) is a transcription factor that plays a major role in metabolic regulation. This review addresses the functional role of PPARα in intermediary metabolism and provides a detailed overview of metabolic genes targeted by PPARα, with a focus on liver. A distinction is made between the impact of PPARα on metabolism upon physiological, pharmacological, and nutritional activation. Low and high throughput gene expression analyses have allowed the creation of a comprehensive map illustrating the role of PPARα as master regulator of lipid metabolism via regulation of numerous genes. The map puts PPARα at the center of a regulatory hub impacting fatty acid uptake, fatty acid activation, intracellular fatty acid binding, mitochondrial and peroxisomal fatty acid oxidation, ketogenesis, triglyceride turnover, lipid droplet biology, gluconeogenesis, and bile synthesis/secretion. In addition, PPARα governs the expression of several secreted proteins that exert local and endocrine functions.

KEYWORDS:

Expression profiling; Lipid metabolism; Liver; Metabolic homeostasis; PPARα; Systems biology; Transcriptional networks

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