Perturbed rhythmic activation of signaling pathways in mice deficient for Sterol Carrier Protein 2-dependent diurnal lipid transport and metabolism.
Through evolution, most of the living species have acquired a time keeping system to anticipate daily changes caused by the rotation of the Earth. In all of the systems this pacemaker is based on a molecular transcriptional/translational negative feedback loop able to generate rhythmic gene expression with a period close to 24 hours. Recent evidences suggest that post-transcriptional regulations activated mostly by systemic cues play a fundamental role in the process, fine tuning the time keeping system and linking it to animal physiology. Among these signals, we consider the role of lipid transport and metabolism regulated by SCP2. Mice harboring a deletion of the Scp2 locus present a modulated diurnal accumulation of lipids in the liver and a perturbed activation of several signaling pathways including PPARα, SREBP, LRH-1, TORC1 and its upstream regulators. This defect in signaling pathways activation feedbacks upon the clock by lengthening the circadian period of animals through post-translational regulation of core clock regulators, showing that rhythmic lipid transport is a major player in the establishment of rhythmic mRNA and protein expression landscape.
Department of Pharmacology and Toxicology, University of Lausanne, Lausanne, CH-1011, Switzerland.|Department of Diabetes and Circadian Rhythms, Nestlé Institute of Health Sciences, CH-1015 Lausanne, Switzerland.
Céline
C
Jouffe
Department of Diabetes and Circadian Rhythms, Nestlé Institute of Health Sciences, CH-1015 Lausanne, Switzerland.|Faculty of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL), CH-1015 Lausanne, Switzerland.
Cédric
C
Gobet
Department of Diabetes and Circadian Rhythms, Nestlé Institute of Health Sciences, CH-1015 Lausanne, Switzerland.
Eva
E
Martin
Functional Genomic, Nestlé Institute of Health Sciences, CH-1015 Lausanne, Switzerland.
Sylviane
S
Métairon
Department of Gastro-Intestinal Health &Microbiome, Nestlé Institute of Health Sciences, CH-1015 Lausanne, Switzerland.
Delphine
D
Morin-Rivron
Department of Gastro-Intestinal Health &Microbiome, Nestlé Institute of Health Sciences, CH-1015 Lausanne, Switzerland.|Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, Toronto, ON, M5S 3E2, Canada.
Mojgan
M
Masoodi
Department of Pharmacology and Toxicology, University of Lausanne, Lausanne, CH-1011, Switzerland.|Department of Diabetes and Circadian Rhythms, Nestlé Institute of Health Sciences, CH-1015 Lausanne, Switzerland.|Faculty of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL), CH-1015 Lausanne, Switzerland.
Frédéric
F
Gachon
D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D057906:Circadian Clocks; D002940:Circadian Rhythm / Q000235:genetics; D016000:Cluster Analysis; D017353:Gene Deletion; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D050356:Lipid Metabolism; D008297:Male; D053858:Metabolic Networks and Pathways; D051379:Mice; D018345:Mice, Knockout; D011499:Protein Processing, Post-Translational; D015398:Signal Transduction
D002352:Carrier Proteins; C072087:sterol carrier proteins