0023 Light- and Meal-induced Phase Resetting of Circadian Lipid Rhythms in Humans

Abstract Introduction We have characterized endogenous circadian rhythms in total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C) and triglycerides (TG) and shown that they can be reset according to a Type I phase response curve (PRC) by a combined stimulus of light exposure and meals. The resulting PRCs are different in phase and amplitude than that describing melatonin rhythm resetting and therefore we hypothesized that lipid rhythms may be reset by meal timing rather than light. In the current study, we are constructing three PRCs that systematically examine the contribution of light and/or meal timing on the circadian resetting response of lipids. Methods To date, 15 young healthy adults (mean age±SD= 25.9±3.6 yrs, 7F) have been randomized to one of three stimulus conditions: Light + Meals (n=5): 6.5-h ~10,000 lux white light exposure with a 12-h meal window; Meals only (n=4): dim light (< 3 lux) with a 12-h meal window; or Time-restricted Meals (n=6): dim light with a 6.5-h meal window. Individuals are randomized to one of 16 stimulus times distributed every 90-minutes (~22.5◦) across the 24-hour day. Cosinor analysis was used to assess 24-h rhythms in lipids measured during constant routines conducted before and after stimulus administration. Phase shifts were calculated as the difference between pre- and post-stimulus acrophase. Results Endogenous circadian rhythms were observed in 73%, 86% and 100% of participants for TC, HDL-C and TG, respectively, during the first CR. These percentages were similar for the second CR: 80% for TC and HDL-C and 93% for TG. Consistent with our previous work, TC and HDL-C peaked in the afternoon (~15:30), whereas TG peaked in the early morning (~03:30). TC, HDL-C and TG demonstrated both advance (up to 7.1 hours) and delay (up to 8.9 hours) phase shifts depending on the circadian time of stimulus administration that were broadly consistent with our published PRCs. Conclusion Once completed, these PRCs will differentiate the role of light versus meals in resetting lipid rhythms, and the impact of meal window duration. This work is essential for providing evidence-based advice to shift workers and others with circadian misalignment to reduce their risk of lipid rhythm desynchrony. Support (if any) R01HL159207