Consumption of a High-fat Diet Alters Transcriptional Rhythmicity in Liver from Pubertal Mice

Introduction: Childhood obesity is associated with adult obesity, which is a risk factor for chronic diseases. Obesity, as an environmental cue, alters circadian rhythms. The hypothesis of this study was that consumption of a high-fat diet alters metabolic rhythms in pubertal mice.

Methods: Weanling female C57BL/6NHsd mice were fed a standard AIN93G diet or a high-fat diet (HFD) for 3 weeks. Livers were collected from six-week-old mice every 4 h over a period of 48 h for transcriptome analysis.

Results And Discussion: The HFD altered rhythmicity of differentially rhythmic transcripts in liver. Specifically, the HFD elevated expression of circadian genes , , and and genes encoding lipid metabolism and , while decreased expression of circadian genes and and lipid metabolism genes , , and . Hierarchical clustering analysis of differential expression genes showed that the HFD-mediated metabolic disturbance was most active in the dark phase, ranging from Zeitgeber time 16 to 20. The Kyoto Encyclopedia of Genes and Genomes enrichment analysis of differentially expressed genes showed that the HFD up-regulated signaling pathways related to fatty acid and lipid metabolism, steroid and steroid hormone biosynthesis, amino acid metabolism and protein processing in the endoplasmic reticulum, glutathione metabolism, and ascorbate and aldarate metabolism in the dark phase. Down-regulations included MAPK pathway, lipolysis in adipocytes, Ras and Rap1 pathways, and pathways related to focal adhesion, cell adhesion molecules, and extracellular matrix-receptor interaction. In summary, the HFD altered metabolic rhythms in pubertal mice with the greatest alterations in the dark phase. These alterations may disrupt metabolic homeostasis in puberty and lead to metabolic disorders.