The overarching goal of this application for a K24 Midcareer Investigator Award in Patient-Oriented Research is to foster training of promising junior investigators in cutting edge patient-oriented research related to how sleep biology influences cardiometabolic health. It capitalizes on the established network and resources of the recently renewed UCLA CTSI that includes a highly successful KL2 program. Dr. Liu led a competitively- funded Endocrine and Cardiometabolic Program in Sleep Biology at the University of Sydney, and since 2012, he has led a similar interdisciplinary research program in Los Angeles supported by a 5 year NHLBI R01 ?Hormonal mechanisms of sleep restriction? that is currently in its 3rd year. During his 10 years of mentoring, he has trained 16 individuals: 10 remaining in academic medicine and 2 others in industry-related patient orientated research. Three of his trainees won major US young investigator awards under his supervision. He continues to support, mentor, and publish with former trainees, often long after they left his laboratory. Disturbed sleep causes insulin resistance, promotes poor food choices, and curtails fat loss while dieting, thereby reducing the effectiveness of standard weight loss programs. However, the cardiometabolic consequences of disturbed sleep are not well recognized by the community, and the evidential bases to justify widespread changes to community sleeping patterns for cardiometabolic health reasons are evolving. Showing the mechanisms by which sleep restriction leads to cardiometabolic ill-health, particularly in older adults according to sex, are critical steps in providing these data. Dr. Liu's goal is to mentor the next cadre of independent clinical scientists focused on placing sleep alongside diet and exercise as part of healthy lifestyle, by understanding hormonal mechanisms and consequences of disrupted, inadequate or misaligned sleep. The work proposed in this application fulfill these goals.
Aim 1 will reveal the hypothalmo-pituitary-adrenal and hypothalamo-pituitary-gonadal mechanisms that cause testosterone-cortisol imbalance when sleep is restricted in older men and women (20 in each group). In doing so, trainees will learn endocrine physiology and chronobiological study design, IRB processes, recruitment skills, and hands-on study management.
Aim 2 will identify sex differences in these mechanisms, trainees will learn statistical methods and abstract/presentation/ manuscript preparation.
Aim 3 requires trainees to discover new mechanisms by which sleep restriction causes insulin resistance and alters appetite or food intake. Certain inflammatory mediators, hormones, or factors related to ethnicity or age could be studied.
Aim 3 fulfils broader expectations for trainees to have a second project that is faster to accomplish, more exploratory, and driven by their interests and available resources, to develop a line of research that complements and is separate from that of the mentors. Taken together, these experiments will generate new knowledge of the relationship between sleep and hormonal cardiometabolic and reproductive health, provide wide-ranging training opportunities, and generate future R and K proposals.
Insufficient sleep is common, and leads to insulin resistance, a major factor in the development of type 2 diabetes mellitus. This proposal attempts to reveal the hormonal mechanisms underlying the link between insufficient sleep with insulin resistance in older adults, the population at greatest risk for disordered sleep and metabolic disorders as a vehicle to provide outstanding mentorship opportunities.
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