It is widely speculated that restricted sleep leads to increased body adiposity and development of risk factors for obesity-related diseases, such as those associated with metabolic syndrome. Empirical studies are few. The objective of this proposal is to determine the effects of sleep restriction on physiological and cellular pathways that are the basis for changes in adiposity and disease corollaries. The central hypotheses states that sleep restriction results in altered lipid metabolism and changes to the adipose tissue phenotype, specifically with regard to its composition of inflammatory cells and secretion of bioactive peptides. The levels of the adipose secretions, in turn, mediate some of the signs associated with sleep restriction. Preliminary data support the feasibility of testing this hypothesis by providing evidence that sleep restriction leads to metabolic imbalance, characterized by marked increases in food consumption but failure to increase storage. This metabolic dysregulation is associated with a mild systemic proinflammatory state and suppression of anabolic hormones, which are signs shared by metabolic syndrome.
Under Aim 1, mediation of clinical and pathological signs induced by sleep restriction by the adipokine leptin will be determined. Completion of this aim will show the clinical meaningfulness of leptin suppression by sleep loss research. Experiments under Aim 2 are designed to test the working hypothesis that multiple sleep restriction and sleep recovery cycles alter the fate of fatty acids by accelerated lipogenesis in white adipose tissue as compared to other organs. Studies under Aim 3 will identify changes in adipose tissue phenotype. The cellular composition and secretion of bioactive peptides and proinflammatory molecules from adipose tissue will be measured. Remodeled adipose tissue in ways that may favor disease processes would be expected to result from metabolic imbalance induced by sleep restriction. The research design is composed of planned comparisons of different amounts of sleep deprivation, and single and multiple cycles of restricted sleep and rebound sleep. The analytical methods include biochemical, immunoassay, and immunohistochemical analyses. The significance of the proposed research is the provision of a tangible, empirical basis of the effects of sleep restriction on metabolic pathways and adipose tissue cells, which can be gainfully explored for ways to alter the clinical course of diseases associated with insufficient sleep.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL086447-04
Application #
7664365
Study Section
Special Emphasis Panel (ZHL1-CSR-H (S1))
Program Officer
Ershow, Abby
Project Start
2006-09-12
Project End
2011-07-31
Budget Start
2009-08-01
Budget End
2011-07-31
Support Year
4
Fiscal Year
2009
Total Cost
$275,278
Indirect Cost
Name
Medical College of Wisconsin
Department
Neurology
Type
Schools of Medicine
DUNS #
937639060
City
Milwaukee
State
WI
Country
United States
Zip Code
53226
Everson, Carol A; Henchen, Christopher J; Szabo, Aniko et al. (2014) Cell injury and repair resulting from sleep loss and sleep recovery in laboratory rats. Sleep 37:1929-40
Everson, Carol A; Folley, Anne E; Toth, Jeffrey M (2012) Chronically inadequate sleep results in abnormal bone formation and abnormal bone marrow in rats. Exp Biol Med (Maywood) 237:1101-9
Everson, Carol A; Szabo, Aniko (2009) Recurrent restriction of sleep and inadequate recuperation induce both adaptive changes and pathological outcomes. Am J Physiol Regul Integr Comp Physiol 297:R1430-40