Dysregulation of Npas2 leads to altered metabolic pathways in a murine knockout model. Mol Genet Metab 2013 Nov;110(3):378-87
Date
09/27/2013Pubmed ID
24067359Pubmed Central ID
PMC3874417DOI
10.1016/j.ymgme.2013.08.015Scopus ID
2-s2.0-84885426304 (requires institutional sign-in at Scopus site) 26 CitationsAbstract
In our primate model of maternal high fat diet exposure, we have described that fetal epigenomic modifications to the peripheral circadian Npas2 are associated with persistent alterations in fetal hepatic metabolism and non-alcoholic fatty liver. As the interaction of circadian response with metabolism is not well understood, we employed a murine knockout model to characterize the molecular mechanisms with which Npas2 reprograms the fetal hepatic metabolic response. cDNA was generated from Npas2-/- and +/+ (wild type) livers at day 2 (newborn) and at 25 weeks (adult) of life. Newborn samples were analyzed by exon array (n = 3/cohort). Independent pathway analysis software determined that the primary dysregulated pathway(s) in the Npas2-/- animals uniformly converged on lipid metabolism. Of particular interest, Ppargc1a, which integrates circadian and metabolism pathways, was significantly (p < .01) over expressed in newborn (1.7 fold) and adult (1.8 fold) Npas2-/- animals. These findings are consistent with an essential role for Npas2 in programming the peripheral circadian response and hepatic metabolism, which has not been previously described.
Author List
O'Neil D, Mendez-Figueroa H, Mistretta TA, Su C, Lane RH, Aagaard KMMESH terms used to index this publication - Major topics in bold
AnimalsBasic Helix-Loop-Helix Transcription Factors
Circadian Rhythm
Cluster Analysis
Gene Expression Profiling
Gene Expression Regulation
Gene Regulatory Networks
Liver
Metabolic Networks and Pathways
Mice
Mice, Knockout
Nerve Tissue Proteins
Reproducibility of Results
Signal Transduction
