Transcriptional regulation of metabolism.
Our understanding of metabolism is undergoing a dramatic shift. Indeed, the efforts made towards elucidating the mechanisms controlling the major regulatory pathways are now being rewarded. At the molecular level, the crucial role of transcription factors is particularly well-illustrated by the link between alterations of their functions and the occurrence of major metabolic diseases. In addition, the possibility of manipulating the ligand-dependent activity of some of these transcription factors makes them attractive as therapeutic targets. The aim of this review is to summarize recent knowledge on the transcriptional control of metabolic homeostasis. We first review data on the transcriptional regulation of the intermediary metabolism, i.e., glucose, amino acid, lipid, and cholesterol metabolism. Then, we analyze how transcription factors integrate signals from various pathways to ensure homeostasis. One example of this coordination is the daily adaptation to the circadian fasting and feeding rhythm. This section also discusses the dysregulations causing the metabolic syndrome, which reveals the intricate nature of glucose and lipid metabolism and the role of the transcription factor PPARgamma in orchestrating this association. Finally, we discuss the molecular mechanisms underlying metabolic regulations, which provide new opportunities for treating complex metabolic disorders.
Desvergne
Béatrice
B
Center for Integrative Genomics, National Centre of Competence in Research Frontiers in Genetics, University of Lausanne, Lausanne, Switzerland.
Michalik
Liliane
L
Wahli
Walter
W
D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D004435:Eating / Q000502:physiology; D005215:Fasting / Q000502:physiology; D006801:Humans; D007333:Insulin Resistance / Q000235:genetics; D050356:Lipid Metabolism; D008659:Metabolic Diseases / Q000188:drug therapy / Q000378:metabolism; D008660:Metabolism / Q000502:physiology*; D047492:Peroxisome Proliferator-Activated Receptors / Q000378:metabolism; D011506:Proteins / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic / Q000502:physiology*
D000596:Amino Acids; D001786:Blood Glucose; D047492:Peroxisome Proliferator-Activated Receptors; D011506:Proteins; D014157:Transcription Factors