Effect of circadian regulation and sleep disruption on metabolic homeostasis, The

2022 Summer.Includes bibliographical references.Sleep and circadian disruption are ubiquitous in modern society. While the National Sleep Foundation recommends adults sleep 7-9 hours per night, the average sleep duration of American adults has decreased from ~8.8 hours to ~6.8 hours over the last century, with 1 in 3 people report sleeping fewer than 6.5 hours per night during the work week. People who sleep fewer than 6 hours per night have a three-fold risk of impaired fasting glucose than those sleeping at least 8 hours per night. Laboratory studies report that as little as one night of insufficient sleep impairs insulin sensitivity, which is a common risk factor for obesity and diabetes. Circadian misalignment is common in people who work non-standard hours, including evening, night, or rotating shifts, and is associated with increased fasting glucose and insulin concentrations, as well as impaired insulin sensitivity. Moreover, circadian misalignment can also occur as a consequence of insufficient sleep. With more than 35% of adults reporting insufficient amounts of sleep, chronic and acute circadian misalignment are likely even more prevalent than commonly recognized. Sleep and circadian disruption are associated with increased mortality rates and health problems, including obesity and diabetes. However, the molecular mechanisms by which these impairments occur are not known. Thus, the overall goal of this dissertation was to determine the circadian rhythms of substrate oxidation and hormonal regulators of energy balance as well as to identify molecular alterations associated with insufficient sleep, including skeletal muscle lipid accumulation and altered gene expression, and their relation with insulin sensitivity. The primary findings are that in healthy, young, lean participants 1) carbohydrate and lipid oxidation as well as ghrelin and peptide YY have circadian rhythms as identified by a constant routine protocol and 2) insufficient sleep induces skeletal muscle lipid accumulation and altered gene expression as well as impaired insulin sensitivity. Together, these studies indicate that sleep and circadian disruption may impair insulin sensitivity via dysregulated lipid metabolism