The current study demonstrates that morning plasma leptin levels increase significantly following 5 nights of partial sleep restriction with ad libitum access to food. Observed increases in plasma leptin levels were maintained with further sleep restriction and decreased with increased sleep opportunity. These findings were consistent across a diverse sample, although women and heavier (higher BMI) participants were observed to have a significantly greater leptin response to sleep restriction compared to men and participants with lower BMIs. Results from the current study provide new evidence that women are differentially vulnerable to the physiological consequences of sleep restriction. Estimated menstrual phase did not have a significant effect on either baseline leptin levels or their response to sleep restriction; as such, it is unlikely that menstrual phase contributed significantly to the greater, and more variable, leptin response among women compared to men. The observed sex differences may, then, be related to physiological (e.g., gonadal steroids, Rosenbaum, Pietrobelli, Vasselli, Heymsfield, & Leibel, 2001
; hypothalamic-pituitary-adrenal axis reactivity, Uhart, Chong, Oswald, Lin, & Wand, 2006
) or psychological differences (e.g., differences in food consumption in response to stress; Zellner et al., 2006
). In any case, it is likely that these differences resulted from an interaction between biological factors and behavioral outcomes (e.g., food choices and amount consumed) in response to stress.
While the majority of experimental sleep-restriction research has enrolled male-only samples, two prior epidemiologic studies have documented increased cardiovascular risk (incident myocardial infarction, hypertension) associated with short sleep durations among women but not men (Cappuccio et al., 2007
; Ikehara et al., 2009
), and one additional study has documented associations between short sleep durations and inflammatory markers (interleukin [IL]-6, high sensitivity C-reactive protein [hs-CRP]) among women but not men (Miller et al., 2009
). Furthermore, the finding that increases in leptin following sleep restriction were significantly greater among women and heavier individuals also has intriguing parallels with epidemiological evidence that rates of both obesity (BMI > 30) and extreme obesity (BMI > 40) are higher among women compared to men and that increases in rates of obesity and extreme obesity from 1988–1994 to 1999–2000 were larger among women (Flegal et al., 2002
). These studies provide additional support for the sex-based difference observed in the current study, which suggests that effects on leptin may be one biological pathway through which women may be more vulnerable to health risks from behavioral factors (e.g., restricted sleep).
Observed increases in leptin during periods of sleep restriction in the current study were similar to percentage changes reported during periods of “overfeeding” (Chin-Chance, Polonsky, & Schoeller, 2000
) and could reflect simply an increased food intake due to increased time awake. However, the increases in leptin levels observed during one study of total sleep restriction with controlled food intake (Shea et al., 2005
) suggest that the findings of the current study are not a result of increased food intake alone. Several studies have reported increases in hunger during fasting or calorically controlled sleep restriction (Schmid et al., 2008
; Spiegel, Tasali, et al., 2004
), but reports of food consumption during sleep restriction have been mixed (Nedeltcheva et al., 2009
; Schmid, Dilba, Halischmid, Jauch-Chara, & Schultes, 2007
). As such, there is some evidence that hunger increases during sleep restriction when access to food is controlled and limited evidence that patterns of food intake may change during sleep restriction. These changes may occur simply as a result of increased time awake (Saper, Chou, & Elmquist, 2002
), as a mechanism to moderate boredom or stress (Dallman et al., 2003
; Vgontzas et al., 2008
), or as part of a more complex interaction with orexin systems associated with maintenance of wakefulness and feeding behaviors (Willie, Chemelli, Sinton, & Yanagisawa, 2001
). It is also possible that food consumption, itself, at an adverse circadian phase (e.g., nighttime) may play a role.
It is a limitation of the current study that exact energy intake and expenditures were not assessed, particularly with respect to changes in leptin between differing amounts of sleep opportunity. Another methodological limitation was the use of a single blood draw per sampling day rather than sampling leptin levels over the course of a 24-hr day. While significant relationships between sleep duration and leptin levels based on a single blood draw have previously been reported in the literature (e.g., Taheri et al., 2004
; van Leeuwen et al., 2009
), this methodology may not adequately capture changes in the diurnal rhythm of leptin in response to sleep restriction (e.g., Mullington et al., 2003
). It is less clear why our study findings differ from those of the one laboratory study that also provided free access to food (Nedeltcheva et al., 2009
), though differences in measurement parameters (fasting compared to nonfasting, 24-hr profile compared to a single blood draw, differences in sample size) suggest that the neuroendocrine response to sleep restriction and food intake may be sensitive to the experimental conditions under which leptin is assessed. The robustness of the current findings across demographic groups (sex, age, race/ethnicity, BMI), however, demonstrates that observed changes in leptin are relatively consistent within our experimental parameters, which more closely resemble the real-world environment than previous studies that strictly controlled or restricted food intake. Additional research is needed to clarify the respective contributions of short- and long-term sleep restriction and food intake on leptin levels and body weight.
While the current findings differ from previous studies that have restricted or controlled food intake and generally observed decreases in leptin levels (Gomez-Merino et al., 2002
; Guilleminault et al., 2003
; Gundersen et al., 2006
; Mullington et al., 2003
; Nindl et al., 2006
; Schmid et al., 2008
; Spiegel, Leproult et al., 2004
; Spiegel, Tasali, et al., 2004
), these disparate findings may still reflect the same epiphenomenon: sleep restriction may cause an initial decrease in leptin levels, which stimulates appetite and results in increased food intake, leading to elevated leptin levels. However, this study is the first to document any differential response across demographic groups within the population.
Findings from the current study are significant because the experimental conditions used more closely resemble the real-world conditions under which sleep restriction occurs—environments where access to food is plentiful and physical activity is limited due to increasingly sedentary lifestyles. Additionally, this study provides novel evidence of a differential vulnerability of women and individuals with higher BMIs to the biological effects of sleep restriction. Results from the current study demonstrate that sleep restriction can result in direct physiological changes that are relevant to obesity, particularly given the prevalence of shortened sleep and increasing rates of obesity in modern society. This research is of relevance to nursing practice as it emphasizes that obtaining adequate sleep is an important health behavior and that inadequate sleep is associated with health risks, as well as identifies populations that may be more vulnerable to the deleterious effects of sleep loss. These findings have both clinical and occupational (e.g., nursing shift work) significance.