Consumption of a high-fat diet alters transcriptional rhythmicity in liver from pube pubertal mice

Authors: Yan, Lin; SUNDARAM, SNEHA - Former ARS Employee; RUST, BRET - Washington State University; DANIEL, PALMER - University Of North Dakota; LUANN, JOHNSON - University Of North Dakota; Zeng, Huawei

Submitted to: Frontiers in Nutrition
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 12/1/2022
Publication Date: 1/4/2023
Citation: Yan, L., Sundaram, S., Rust, B., Daniel, P., Luann, J., Zeng, H. 2023. Consumption of a high-fat diet alters transcriptional rhythmicity in liver from pube pubertal mice. Frontiers in Nutrition. 9. Article 1068350. https://doi.org/10.3389/fnut.2022.1068350.
DOI: https://doi.org/10.3389/fnut.2022.1068350

Interpretive Summary: The biological clocks exist in all organs in our bodies. It cycles for approximately every 24 hours and controls the daily rhythms of our life (for example, sleep vs. awake, eating vs. fasting). Our dietary practice, as an environmental cue, can alter the rhythms of the clock and affect our health and wellbeing. Childhood obesity is prevalent in the U.S. It is associated with adulthood obesity and related diseases, including metabolic syndrome, heart diseases, and cancer. We investigated whether a high-fat diet, as a change in dietary practice, altered the biological clock and its impact on metabolism in pubertal mice. We found that the high-fat diet, compared to a normal control diet, altered the diurnal expression of clock genes, genes that regulate lipid metabolism, and metabolic pathways related to lipid, protein, and energy metabolism in livers of pubertal mice. Most importantly, the high-fat diet induced alterations occur in the dark phase of the day (the active phase for laboratory rodents). Findings from this study demonstrate that consumption of a high-fat diet in the pubertal age alters the biological clock and leads to metabolic disturbance. It indicates the importance of a healthy dietary practice in childhood for development and growth.

Technical Abstract: Childhood obesity is associated with adulthood obesity. It is a risk factor for chronic diseases in adulthood. Obesity, as an environmental cue, alters circadian rhythm. We hypothesized that consumption of a high-fat diet alters metabolic rhythms in pubertal mice. Weanling female C57BL/6 mice were fed a standard AIN93G diet or a high-fat diet (HFD) for three weeks. Livers were collected from six-week-old mice every four hours over a period of 48 hours for transcriptome analysis. The HFD altered oscillating expression of circadian genes and genes encoding fatty acid and lipid metabolism. The HFD elevated expression of circadian genes Clock, Per1, and Cry1 and genes for lipid metabolism Fads1 and Fads2, while decreased expression of circadian genes Bmal1 and Per2 and lipid metabolism genes Acaca, Fasn, and Scd1. Differential gene expression analysis showed that the HFD-mediated metabolic disturbance was most active in the dark phase, ranging from Zeitgeber time16 to 20. The Kyoto Encyclopedia of Genes and Genomes enrichment analysis of differentially expressed genes showed that the HFD upregulated 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. Downregulations included lipolysis in adipocytes, MAPK pathway, Ras and Rap1 pathways, and pathways related to extracellular matrix-receptor interaction, focal adhesion, and cell adhesion molecules. In summary, the HFD altered metabolic rhythms in pubertal mice with the greatest alterations in the dark phase. These alterations may disrupt the metabolic homeostasis in puberty and lead to metabolic disorders.