title: Ontogeny of hepatic energy metabolism genes in mice as revealed by RNA-sequencing.
abstract: The liver plays a central role in metabolic homeostasis by coordinating synthesis, storage, breakdown, and redistribution of nutrients. Hepatic energy metabolism is dynamically regulated throughout different life stages due to different demands for energy during growth and development. However, changes in gene expression patterns throughout ontogeny for factors important in hepatic energy metabolism are not well understood. We performed detailed transcript analysis of energy metabolism genes during various stages of liver development in mice. Livers from male C57BL/6J mice were collected at twelve ages, including perinatal and postnatal time points (n = 3/age). The mRNA was quantified by RNA-Sequencing, with transcript abundance estimated by Cufflinks. One thousand sixty energy metabolism genes were examined; 794 were above detection, of which 627 were significantly changed during at least one developmental age compared to adult liver. Two-way hierarchical clustering revealed three major clusters dependent on age: GD17.5-Day 5 (perinatal-enriched), Day 10-Day 20 (pre-weaning-enriched), and Day 25-Day 60 (adolescence/adulthood-enriched). Clustering analysis of cumulative mRNA expression values for individual pathways of energy metabolism revealed three patterns of enrichment: glycolysis, ketogenesis, and glycogenesis were all perinatally-enriched; glycogenolysis was the only pathway enriched during pre-weaning ages; whereas lipid droplet metabolism, cholesterol and bile acid metabolism, gluconeogenesis, and lipid metabolism were all enriched in adolescence/adulthood. This study reveals novel findings such as the divergent expression of the fatty acid β-oxidation enzymes Acyl-CoA oxidase 1 and Carnitine palmitoyltransferase 1a, indicating a switch from mitochondrial to peroxisomal β-oxidation after weaning; as well as the dynamic ontogeny of genes implicated in obesity such as Stearoyl-CoA desaturase 1 and Elongation of very long chain fatty acids-like 3. These data shed new light on the ontogeny of homeostatic regulation of hepatic energy metabolism, which could ultimately provide new therapeutic targets for metabolic diseases.
authors.affiliation: Department of Internal Medicine, University of Kansas Medical Center, Kansas City, Kansas, United States of America.
authors.forename: Helen J
authors.initials: HJ
authors.lastname: Renaud
authors.affiliation: Department of Internal Medicine, University of Kansas Medical Center, Kansas City, Kansas, United States of America.
authors.forename: Yue Julia
authors.initials: YJ
authors.lastname: Cui
authors.affiliation: Department of Pharmacology, SUNY Upstate Medical University, Syracuse, New York, United States of America.
authors.forename: Hong
authors.initials: H
authors.lastname: Lu
authors.affiliation: Department of Pharmaceutical Sciences, University of Connecticut School of Pharmacy, Storrs, Connecticut, United States of America.
authors.forename: Xiao-bo
authors.initials: XB
authors.lastname: Zhong
authors.affiliation: College of Medicine, University of Kansas, Kansas City, Kansas, United States of America.
authors.forename: Curtis D
authors.initials: CD
authors.lastname: Klaassen
mesh_terms: D000375:Aging / Q000378:metabolism*; D000818:Animals; D004734:Energy Metabolism / Q000502:physiology*; D005786:Gene Expression Regulation / Q000502:physiology*; D008099:Liver / Q000378:metabolism*; D008297:Male; D051379:Mice; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D017423:Sequence Analysis, RNA
chemical_list: D012333:RNA, Messenger
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