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.
Highlights
The liver plays a central role in sustaining metabolic homeostasis by maintaining a constant supply of energy fuels to bodily tissues
Expression of genes involved in energy metabolism at different life stages An average of 175 million reads were generated per sample by RNA-Seq and more than 80% of these reads were mapped to the mouse genome using TopHat
The mRNA expressions of 1060 genes that encode factors with known roles in energy metabolism were determined in livers of mice at twelve different ages
Summary
The liver plays a central role in sustaining metabolic homeostasis by maintaining a constant supply of energy fuels to bodily tissues It is the critical relay point for the reception of energy substrates arising from food digestion or degradation of endogenous sources, their metabolic conversion or storage, and the final redistribution to bodily tissues. During prolonged fasting or starvation, the liver breaks down fatty acids through a process known as ketogenesis to produce ketone bodies that can be used by most extrahepatic tissues as an energy substrate These processes are inhibited following ingestion of a meal, concomitant with stimulation of hepatic glycogen synthesis (glycogenesis), primarily in response to high circulating insulin levels [reviewed in [4]]. FFAs are subsequently esterified into triglycerides, and packaged into VLDL particles that are exported and stored in other tissues as an additional energy substrate
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
