BACKGROUND: Cardiovascular disease is a leading cause of death worldwide. The cardiovascular system exhibits rhythms in heart rate, blood pressure, and metabolic substrate usage, driven by the circadian clock, a 24-hour transcriptional-translational feedback loop that regulates rhythmic gene expression. Previous work in our lab showed that ~13% of cardiac genes are rhythmically expressed in mice entrained to a 12:12 light:dark (L:D) cycle. However, many of these genes lose rhythmicity under circadian (constant dark D:D) conditions. This suggests that light influences the expression of certain genes in the heart, but the specific light-responsive genes and their role in cardiovascular health are unknown. We hypothesized that light alters expression of cardiac genes important for heart health. METHODS: C57BL/6 mice were entrained to a L:D cycle for 2 weeks, then separated into L:D or D:D conditions (n=24/group). Mice were sacrificed at 4-hour intervals beginning at 1 h before lights-on, at Zeitgeber Times (ZT) 23, 03, 07, 11, 15, and 19, and equivalent time points for D:D mice (Circadian time CT 23, 03, 07, 11, 15 and 19) (n=4/timepoint). Left ventricles were collected and stored at -80ºC. RNA was isolated using Trizol and gene expression profiled on Affymetrix Mouse Gene 2.0ST microarrays. Agilent GeneSpring was used for analyses, filtering genes with >1.5-fold-change (FC) at the dark to light transition. RESULTS: Of 33,793 transcripts analyzed, 52 genes exhibited >1.5 FC in L:D (ZT23-ZT03) but not D:D (CT23-CT03), indicating light responsiveness. Two light-regulated candidates with roles in lipid metabolism were selected for further study based on relative fluorescence units (RFU). Uncoupling protein 3 (Ucp3) expression increased more strongly in LD (ZT23: 58±5 RFU vs. ZT03: 104±18 RFU; 1.79 FC) than DD (CT23: 61±7 RFU vs. CT03: 72±10 RFU; 1.18 FC). UCP3 supports mitochondrial fatty acid oxidation. Pyruvate dehydrogenase kinase 4 (Pdk4) showed a greater L:D-dependent upregulation (ZT23: 710±69 RFU vs. ZT03: 1385±216 RFU; 1.95 FC) than D:D (CT23: 647±87 RFU vs. CT03: 753±60 RFU; 1.16 FC). PDK4 inhibits glucose oxidation to promote fatty acid use. Given the heart’s reliance on fatty acid metabolism, disruption of these light-responsive pathways, such as during shift work, may contribute to lipid imbalance and cardiovascular disease. Future studies will test these effects under altered L:D cycles. CONCLUSION: We provide evidence that environmental light cues influence cardiac lipid-metabolism genes Ucp3 and Pdk4, supporting a role for environmental light in regulating cardiac energy homeostasis. These pathways may represent therapeutic targets for improving cardiovascular health under circadian disruption. FUNDING SOURCES: Canadian Institute of Health Research (CIHR) and Heart and Stroke Foundation of Canada grants to T.A.M. This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.
Li et al. (2026) studied this question.