Abstract 760: Alteration to transcriptional rhythmicity in mammary glands from pubertal MMTV-PyMT mice fed a high-fat diet

Abstract

Abstract Biological clocks, existing in all human organ systems, cycle every 24 hours in a diurnal pattern and control the daily rhythms of human life (e.g., eating vs. fasting, sleep vs. wakefulness), which is essential for health and wellbeing. Disruption of the biological clocks, either by genetic or environmental alteration, disturbs circadian rhythms, which may lead to chronic diseases. Childhood obesity is a risk factor for breast cancer in adult women. Lifestyle changes in the modern world (e.g., energy-dense diets) serve as environmental factors that contribute to alterations in biological clocks and obesity. The present study examined transcriptional rhythmic changes in mammary glands from pubertal MMTV-PyMT mice fed a high-fat diet (HFD). Three-week-old female mice (FVB background) were randomly assigned into three groups - wild-type (WT) mice fed the AIN93G diet and MMTV-PyMT mice fed the AIN93G diet or an HFD for three weeks. At the end of the study, mammary glands were collected every 4 hours over a period of 24 hours (Zeitgeber time 0-24 hours) for RNA-sequencing analysis. The mammary weight was 0.45±0.02, 0.59±0.02, and 0.67±0.02 g for WT mice fed the AIN93G diet and MMTV-PyMT mice fed the AIN93G and HFD, respectively (means ± SEM, all p<0.05 when three groups were compared each other). The rhythmicity analysis using R showed that greater than 1,000 transcripts were classified as “loss of rhythm” when MMTV-PyMT mice (both AIN93G-fed and HFD-fed groups) were compared to WT mice fed the AIN93G diet. Eighteen transcripts were classified as “loss of rhythm” in MMTV-PyMT mice when the HFD was compared to AIN93G diet. Hierarchical clustering analysis showed differentially expressed genes that were significantly altered and KEGG enrichment analysis showed the most upregulated and downregulated metabolic pathways in treatment groups than in the control group at each time point over the 24-hour period. These findings indicates that genetic alterations may have a greater effect than dietary effects on transcriptional rhythmicity in mammary glands from pubertal mice. Citation Format: Lin Yan, Daniel G. Palmer, Huawei Zeng. Alteration to transcriptional rhythmicity in mammary glands from pubertal MMTV-PyMT mice fed a high-fat diet [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 760.