THE EFFECTS OF SLEEP RESTRICTION AND SUBSEQUENT SLEEP RECOVERY ON GLYCEMIC AND LIPEMIC METABOLISM
Open Access
- Author:
- Ness, Kelly
- Graduate Program:
- Integrative and Biomedical Physiology
- Degree:
- Doctor of Philosophy
- Document Type:
- Dissertation
- Date of Defense:
- May 20, 2019
- Committee Members:
- Gregory C Shearer, Dissertation Advisor/Co-Advisor
Orfeu M Buxton, Committee Chair/Co-Chair
Penny Margaret Kris-Etherton, Committee Member
Anne-Marie Chang, Committee Member
Andrew David Patterson, Outside Member
Orfeu M Buxton, Dissertation Advisor/Co-Advisor - Keywords:
- Sleep restriction
Metabolism
Glycemia
Lipemia
NEFA
Non-esterified fatty acids
Triglycerides
Postprandial metabolism
Interleukin-6
Oxylipins
Adipose tissue
Adipocytes - Abstract:
- Adults that sleep fewer than seven hours per night on a regular basis are at greater risk of developing a number of cardiometabolic diseases including type 2 diabetes (T2D), cardiovascular disease (CVD), and obesity. Laboratory studies have demonstrated that sleep restriction, or inadequate sleep, decreases whole-body insulin sensitivity. Recent research indicates that sleep restriction also decreases adipocyte insulin sensitivity, however the mechanisms underlying this change and the functional and metabolic consequences of this change remain unknown. Furthermore, very little is known about the metabolic recovery time course following a bout of inadequate sleep. Therefore, we performed an 11-day sleep restriction study (n = 15) to characterize the effects of sleep loss on functional adipocyte insulin response, lipemic and glycemic postprandial metabolism, and on adipocyte and plasma lipid signaling. For the first three nights of the study, the baseline condition, participants continued a ten-hour time in bed (TIB) per night routine that they began at home the week prior (22:00-08:00). For the next five nights, participants’ sleep was restricted to five hours TIB/night from 00:30-05:30. For the final two nights, the recovery condition, participants resumed the ten-hour TIB/night routine (22:00-08:00). To address our research hypotheses we repeated a series of metabolic assessments once during each condition of the study, the results of which are the subject of this dissertation. For the first endpoint, we assessed the effects of sleep restriction on the characteristic suppression and rebound of non-esterified fatty acids (NEFA) during an intravenous glucose tolerance test (IVGTT). In response to insulin, healthy adipocytes suppress intracellular lipolysis, causing a rapid decline in plasma NEFA levels which is quantifiable and predictable. We hypothesized that we could quantify the effects of sleep restriction on functional adipocyte insulin sensitivity by measuring time-dependent changes in NEFA kinetics during an IVGTT. Furthermore, we hypothesized that two nights of recovery sleep would be sufficient to restore whole-body glucose metabolism to baseline levels. We found that, compared to baseline, sleep restriction significantly delays the NEFA rebound following IVGTT-induced suppression (p = 0.01) and that two nights of ten hours TIB/night recovery sleep was not sufficient to restore insulin sensitivity (p = 0.003). For the second endpoint, we assessed the effects of sleep restriction on the postprandial metabolism of a high-fat dinner (HFD). Given what is known about the effects of sleep restriction on insulin sensitivity, adipocyte metabolism, and long-term chronic disease risk, we predicted that sleep restriction would impair postprandial metabolism and increase postprandial lipemia. We found that sleep restriction to five hours/night for four nights impaired whole-body insulin sensitivity as evidenced by increased insulin levels (p = 0.05). Sleep restriction also decreased postprandial triglyceride area under the curve (p = 0.01), decreased participant reported satiety following the meal (p = 0.03), and decreased postprandial interleukin-6 (p < 0.01). In the case of postprandial metabolism, one night of recovery sleep was sufficient to restore these measures to baseline levels. For the third endpoint, we assessed the effects of sleep restriction on adipose tissue and plasma esterified and unesterified oxylipin signaling in a subset of participants (n = 5). Oxylipins are modified polyunsaturated fatty acids that act as autocrine and paracrine signaling molecules. There are hundreds of known oxylipins with wide-ranging signaling effects throughout the body’s cell and tissue types. Furthermore, oxylipins exist in two pools: unesterified oxylipins in the cytoplasm or plasma make up the active signaling pool, while esterified oxylipins have been sequestered into lipid bilayers and can be hydrolyzed (released from sequestration) to act as inter- or intracellular signals at a later time. Certain oxylipins, such as the arachidonic acid epoxides (EpETrEs), can be produced in the adipose tissue and are known to affect adipocyte insulin signaling. EpETrEs may therefore be involved in the decrements in adipocyte insulin sensitivity induced by sleep restriction. We hypothesized that insulin-sensitizing metabolites would be decreased in the unesterified fraction, or the bioactive lipid signaling pool, of adipose tissue and plasma oxylipins. We found that sleep restriction significantly decreased unesterified adipose tissue EpETrEs (p = 0.05), among other metabolites. Our data, when taken in light of the body of evidence, indicate that sleep restriction may increase lipid metabolism and clearance from the plasma. This could be one of the mechanisms by which sleep restriction decreases whole-body insulin sensitivity, as NEFA are the preferred fuel source for skeletal muscle and, via the Randle cycle, competitively inhibit skeletal muscle glucose oxidation. Our findings also suggest that lipid signaling is affected by sleep restriction and may play a role in decreasing adipocyte insulin sensitivity. Together, these data provide insight into the mechanisms linking short-term sleep restriction with decreased insulin sensitivity and chronic inadequate sleep with increased cardiometabolic disease risk. Further, they suggest exciting new lines of inquiry on the mechanisms linking sleep and metabolism.