Meal timing alone alters lipid oxidation rate without affecting corticosterone in mice and humans
Kelly, Kevin Parsons
Circadian misalignment has been implicated in obesity prevalence among shift workers. It is thought these effects are in part due to the misalignment of meals in relation to the circadian clock. Meal timing is a known zeitgeber that can interact directly with the clock complex: however, the mechanism and pathways involved are not well understood. Recent research suggests that circadian meal timing alone can alter weight gain in mammals, primarily by changes in the length of the feeding duration causing changes in energy expenditure. However, these clear effects in mice are countered by conflicting results in human studies. It is also unclear if these changes in metabolism are driven by a corticosterone response, as corticosterone has been implicated in both fasting response and has been found to be misaligned in shift work models. In my dissertation, I attempted to isolate the metabolic effects seen in mice and humans of meal timing onset/offset compared to feeding duration. I find in mice that both altering feeding duration and altering meal timing are able to cause weight gain resistance in mice. I find that changing only the onset/offset of meal timing acts on metabolism differently than changing feeding duration by altering the carbohydrate/lipid oxidation rates without altering energy expenditure seen in feeding duration studies. I show that the effects on mouse metabolism due to changes in onset/offset of feeding are also reproducible in humans. Human subjects given meals closer to the end of the inactive phase show less lipid oxidation compared to meals given at the beginning of the active phase, without impacting energy expenditure. I show that the corticosterone response is unaltered by changes in feeding duration or onset/offset of meal timing. Finally, I show that large metabolic regulators AMPK and MTOR are able to alter period of individual cell lines in a temperature dependent manner, offering a potential mechanism for meal timing to influence the clock. Together, my work shows that weight gain effects seen in circadian meal timing are due to short term effects on carbohydrate/lipid oxidation and changes to energy expenditure is dependent on feeding duration.