Adverse obesity-related cardiometabolic outcomes of circadian misalignment in adolescents
Restricted (Penn State Only)
- Author:
- Morales, Natasha
- Graduate Program:
- Anatomy
- Degree:
- Doctor of Philosophy
- Document Type:
- Dissertation
- Date of Defense:
- September 17, 2024
- Committee Members:
- Pat Mclaughlin, Program Head/Chair
Pat Mclaughlin, Major Field Member
Amy Arnold, Major Field Member
Anne-Marie Chang, Outside Unit & Field Member
Julio Fernandez-Mendoza, Chair & Dissertation Advisor
Duanping Liao, Major Field Member - Keywords:
- Adolescence
Visceral adipose tissue
Obesity
Circadian misalignment
Cardiometabolic health - Abstract:
- Adolescence is a critical developmental period marked by physical and psychosocial changes. With the onset of puberty, there is a shift in the circadian timing of the sleep-wake cycle towards eveningness, causing youth’s sleep phases to occur later than during their childhood years. This shift may conflict with early morning school schedules, extended extra-academic responsibilities, and social/leisure activities. As a result, adolescents may experience different forms of circadian misalignment, such as a delayed sleep phase, sleep irregularity and social jetlag, which are novel risk factors for obesity and its related cardiometabolic morbidity. Visceral adiposity is particularly detrimental during adolescence because it is a hormonally active fat tissue with biochemical properties capable of causing metabolic dysfunction. Although insufficient sleep is recognized as a risk factor for cardiometabolic health, recent data indicate that circadian misalignment may also be one. However, from a mechanistic perspective, the role of circadian misalignment in the impact of visceral adiposity on cardiometabolic morbidity in adolescents remains poorly understood. This dissertation examined whether circadian misalignment of the sleep-wake cycle increases the cardiometabolic risk associated with visceral adiposity in 421 adolescents of the Penn State Child Cohort (median age 16, 48.8% female, 22.4% racial/ethnic minority). Specific aims 1 and 2 showed that 1) A delayed and an irregular timing of sleep during schooldays and during vacation, respectively, increase the impact of visceral adiposity on elevated blood pressure; 2) A delayed, irregular, and socially jetlagged timing of sleep during schooldays increase the impact of visceral adiposity on metabolic syndrome; and 3) An irregular and a delayed timing of sleep during schooldays and during vacation, respectively, are associated with blunted heart rate variability, an association that was further confirmed through longitudinal analyses from childhood to adolescence. Exploratory aim 3 suggested that 1) Males experience greater delay in the timing of their sleep, yet females are more vulnerable to the impact of circadian misalignment on the association of visceral adiposity with elevated blood pressure and metabolic syndrome; and 2) Racially/ethnically minoritized adolescents experience greater delay and irregularity in the timing of their sleep and are more vulnerable to the impact of circadian misalignment on the association of visceral adiposity with elevated blood pressure and metabolic syndrome, yet non-Hispanic white adolescents are more vulnerable to the association of circadian misalignment with blunted heart rate variability. Collectively, these data show that deviations in the circadian timing of sleep contribute to the increased cardiovascular and metabolic sequelae associated with obesity and that distinct metrics of circadian misalignment require measurement under different entrainment conditions in adolescents (i.e., during the school year and during vacation). Furthermore, our data are commensurate with prior studies showing sleep health disparities as a function of sex and race/ethnicity and expand upon this by demonstrating that females and minoritized adolescents are more vulnerable to the impact of circadian misalignment on cardiometabolic health outcomes. From a biomedical standpoint, future studies should examine the endogenous pathways that explain the impact of circadian misalignment on cardiometabolic health. From a preventative standpoint, these findings highlight the need for early identification of delayed, irregular, and socially jetlagged sleep patterns, particularly in vulnerable adolescents. From a clinical standpoint, early identification can lead to actionable therapeutic interventions, whether contextual, behavioral, photic, or pharmacological, targeting circadian misalignment. From a public policy standpoint, these data indicate that greater efforts should be made to align school start-times and extra-curricular activities with adolescents’ maturational shift in their sleep phase, while protecting them from developing circadian misalignment and its downstream effects on cardiometabolic health.