Sleep restriction is strongly associated with increased body weight, in part through its effects on appetite regulation and energy homeostasis. Two key hormones, leptin and ghrelin, play antagonistic roles in fine-tuning appetite. Leptin, primarily secreted by white adipose tissue, signals satiety and suppresses food intake, whereas ghrelin, secreted mainly by the stomach, stimulates hunger [51]. Perturbations in the balance of these hormones can disrupt normal appetite regulation, promoting overeating and consequent weight gain. Sleep loss increases ghrelin and reduces leptin levels, thereby increasing caloric intake and promoting adiposity. These sleep loss–induced hormonal perturbations provide a mechanistic link between insufficient sleep and obesity risk [51]. In a trial with 19 healthy lean men, sleep restriction was associated with elevated ghrelin levels, particularly in the evening, and led to increased consumption of foods with high sugar content. This occurred despite leptin levels being unaffected [51]. Many other studies have also replicated these findings [52, 53]. Meanwhile, leptin levels drop with sleep deprivation. For instance, in a study of 44 young, healthy subjects (20 women and 24 men), sleep restriction resulted in significantly lower leptin levels and higher ghrelin levels [54].

There is ample evidence that suggests a concurrent decline in societal sleep duration with rising obesity rates [55], highlighting a potential behavioral contributor. A meta-analysis of several population-based studies demonstrated that habitual short sleep (≤ 6 h per night) increased the odds of obesity by 1.40 (95% CI 1.12–1.73) after adjusting for other variables [56].

In addition to weight gain, experimental sleep loss is associated with increased visceral abdominal adiposity. In a cohort of 12 healthy adults, sleep restriction to 4 h per night for 14 days resulted in a significant increase in abdominal fat, accompanied by higher protein and fat intake [57]. In another study with a larger cohort of 225 subjects (44% female), sleeping 4 h per night for 5 nights resulted in a 1-kg weight gain, compared with only 100 g of weight gain in the control group who slept 10 h per night. This was associated with increased caloric and fat intake in the sleep-restricted group [58]. Energy expenditure was not higher in the sleep-restricted group, but caloric consumption was, hence a primary reason for weight gain [59].

In addition to increased caloric intake, sleep deprivation tends to increase caloric intake from snacks and other “unhealthy” food choices. This is independent of changes in leptin and ghrelin levels. Nedeltcheva et al. assigned 11 healthy participants (5 women and 6 men) to either partial sleep deprivation (PSD) (5.5 h in bed) or a normal sleep condition (8.5 h in bed) for 2 weeks. The data from the PSD period was compared to the normal sleep period for each participant. Subjects had unrestricted access to food, and their daily caloric intake and physical activity were monitored. During the sleep-restricted period, average daily caloric intake increased by approximately 300 kcal relative to the normal sleep condition. In addition, more daily calories came from high-carbohydrate snacks in the PSD condition than in normal sleep conditions: 1087 ± 541 cal a day vs 866 ± 365 cal a day [60]. In a 2019 meta-analysis of 17 studies, Zhu et al. demonstrated that PSD resulted in 252.8 (95% CI, 59.1–446.5, P = 0.011) more daily calories consumed than under normal sleep conditions [61].

The sensation of hunger, or the desire to eat, is distinct from the actual behavior of overeating. This distinction raises the question of whether sleep deprivation is directly linked to increased food intake. In the same meta-analysis, Zhu et al. examined 15 studies that measured hunger on a visual analogue scale under both PSD and TSD conditions. Compared to normal sleep, subjective hunger increased by an average of 7.5 mm (95% CI 0.9–14.1, P = 0.027) with PSD, and, by an average of 22.8 mm (95% CI 9.7–35.9, P = 0.001) with TSD [61]. Broussard et al. in 2016 demonstrated similar findings regarding increased snack and carbohydrate consumption. They also linked it to an increase in evening ghrelin levels under PSD compared to normal sleep [51].

All this can impact weight. Zhu et al. in the same meta-analysis, examined weight changes across 10 studies, all using PSD. Over the duration of the study, ranging from 114 nights, the mean increase in weight with PSD was 0.34 kg (95% CI 0.11–0.57, P = 0.003) [61].

Early hypotheses proposed that hormonal alterations during sleep restriction might represent a normal adaptation to increased caloric demands associated with extended wakefulness, even under sedentary conditions [62]. However, this notion has been largely refuted. Several studies reviewed by Reutrakul and Van Cauter (2018), including that of Nedeltcheva et al. (2009), outlined previously, demonstrate that sleep curtailment has minimal or no effect on total energy expenditure [48, 60]. Even under conditions of TSD, energy expenditure increases by only ~ 134 kcal over 24 h compared with 8 h of sleep [63], and in some studies, these differences fail to reach statistical significance when compared to the same baseline of 8 sleep hours [64]. Thus, the long-held belief that sleep serves primarily as an energy-conserving process is no longer supported. In fact, many sleep-dependent physiological processes are metabolically demanding, with some exceeding the energy costs of wakefulness [65]. Importantly, the modest increase in energy expenditure during sleep loss is far outweighed by a concomitant increase in caloric intake and reductions in physical activity [48]. Collectively, this imbalance between higher caloric intake and lower energy expenditure represents another piece of the mechanistic puzzle linking chronic sleep deprivation to obesity.

Sleep deprivation not only increases total caloric intake but also alters food preferences. Across multiple studies, sleep-restricted individuals exhibit heightened cravings for energy-dense foods, particularly snacks with high sodium content (e.g., chips, popcorn, olives), high sugar content (e.g., cake, cookies, ice cream), and starchy carbohydrates (e.g., pasta, bread, potatoes). On average, these cravings increase by 30–40% relative to baseline, depending on individual preference. In contrast, intake of protein-rich foods, dairy, fruits, vegetables, and fatty foods increases only modestly, by approximately 10–15% following insufficient sleep [48, 66]. These findings further reinforce that sleep loss is strongly associated with the consumption of highly palatable, calorie-dense foods, thereby contributing to a positive energy balance and potential weight gain.

From a neurobiological perspective, sleep loss also perturbs the regulation of energy homeostasis by altering lipid-derived metabolites known as endocannabinoids. As their name implies, these endogenous ligands structurally resemble and functionally mimic exogenous cannabinoids, such as those found in recreational or medical cannabis, and similarly activate cannabinoid receptors, promoting increased appetite. Under normal conditions, endocannabinoid concentrations peak in the early afternoon, coinciding with habitual mealtimes, and decline to a minimum around midnight [67]. In 2016, Hanlon et al. randomised 14 healthy lean adults (11 men and 3 women) to 4 nights of normal sleep (up to 8.5 h) and 4 nights of sleep restricted to 4.5 h. When sleep-deprived, the circulating levels of the endocannabinoid 2-arachidonoylglycerol (2-AG) and its analog 2-oleoylglycerol (2-OG) declined more slowly in the evening and were higher near the end of the day than when subjects had normal sleep. They concomitantly assessed hunger, appetite, and food intake under controlled conditions. This insufficient-sleep-induced upregulation of the endocannabinoid system correlated with increased hedonic (snack-concentrated) food intake. This sleep deprivation–induced surge in circulating endocannabinoids, together with concomitant alterations in leptin and ghrelin, may synergistically underlie the overconsumption of calorie-dense foods, thereby increasing the risk of weight gain and obesity [67].

To elucidate the neural mechanisms underlying sleep loss–induced shifts in food preference. In 2013, Greer et al. enrolled 23 healthy, lean adults in a study with 2 experimental conditions separated by at least 1 week: a full-night sleep condition and a TSD condition. During each session, participants viewed 80 food images ranging from low- to high-calorie items, rating their desire for each item on a 1–4 scale while undergoing functional MRI scanning [68]. Following the scan, participants were provided with a serving of the food they rated highest in desire, ensuring that the ratings reflected genuine appetitive motivation rather than experimental demand characteristics [68]. This design allowed the investigators to directly link neural activity patterns to self-reported food craving under well-rested and sleep-deprived states [68]. Hence, using within-subject comparisons of brain activity across sleep conditions provided robust evidence for the neural mechanisms linking sleep deprivation to altered eating behavior. Specifically, sleep loss increased amygdala activation, a key limbic structure involved in emotional and reward processing, in response to images of palatable, energy-dense foods. Concurrently, activity in the prefrontal cortex, which mediates executive control and decision-making, was attenuated. This functional imbalance (heightened hedonic signaling coupled with impaired impulse control) was associated with a significant shift in food preferences toward high-calorie items. Quantitatively, sleep-deprived participants exhibited an average increase of ~ 600 kcal in desired food intake. In contrast, sufficient sleep restored functional connectivity between the prefrontal cortex and subcortical reward centers, facilitating top-down regulation of hedonic drives and supporting behavioral restraint in food consumption [69]. These findings add a neural dimension to the mechanistic picture, highlighting how sleep deprivation interacts with hormonal and behavioral pathways resulting in hyperphagia and weight gain.

Beyond hormonal and neurocognitive alterations, recent evidence highlights a link between sleep loss and dysbiosis of the gut microbiome. The intestinal microbiome (a complex ecosystem of bacteria, fungi, protozoa, and viruses that affect the enteric nervous system, or ENS) plays a central role in maintaining overall gut metabolic and immune homeostasis. Dominant bacterial phyla include Bacteroidetes and Firmicutes, whose relative abundance is typically balanced in healthy individuals [70]. Sleep disruption has been shown to perturb this balance, decreasing Bacteroidetes while increasing Firmicutes [71]. Notably, alterations in the Bacteroidetes-to-Firmicutes ratio have been associated with weight gain and obesity in both animal and human models [72]. They may predispose individuals to insulin resistance and T2DM under chronic conditions. Mechanistically, elevated cortisol (a hallmark of stress-induced sympathetic activation during sleep deprivation) is associated with the proliferation of pathogenic bacteria [73], thereby contributing to a spectrum of gastrointestinal and metabolic disturbances [74].

Lastly, circadian misalignment can lead to weight gain and an increase in prevalence of obesity and metabolic syndrome. Shift work, for instance, is associated with increased proinflammatory and a decline in anti-inflammatory proteins. In a group of 15 healthy male shiftworkers, 24-h tumor necrosis factor alpha and interleukin 6 levels were higher than those in the control group of 7-day workers. In addition, adiponectin, an anti-inflammatory protein that regulates metabolism and reduces insulin resistance, was lower in the shift work group suggesting a mechanism by which circadian disruption can lead to metabolic syndrome and obesity [75]. Similarly, cortisol levels and insulin resistance were higher in the shift work group [76].

Social jet lag, or a large variation between sleep timing and chronotype that results in sleep deprivation, is associated with higher prevalence of obesity. In a cohort of 815 community-dwelling adults (605 non-obese, 100 obese without comorbidities, and 85 obese with metabolic syndrome), individuals with obesity and metabolic comorbidities exhibited significantly greater social jet lag, measured in hours, than the other 2 groups [77]. Across the cohort, increasing degrees of social jet lag (0–3 h) were associated with progressive elevations in inflammatory and metabolic markers, including C-reactive protein and glycated hemoglobin (HbA1c) [77]. Moreover, greater social jet lag (in hours) was associated with higher body mass index (BMI), greater fat mass (in kilograms), and larger waist circumference [77].

Roenneberg et al. queried their chronotype database of 65,000 unique entries and found that BMI increased commensurate with the magnitude of social jet lag and reduction in sleep duration during the workweek [78]. Mota and her colleagues collected social jet lag and nutritional data from 792 individuals (73% women with a mean age 55.9 ± 12.4 years). Social jet lag was associated with higher caloric intake, particularly after 9 PM, as well as evening snacking and higher fat consumption [79].

These associations extend to pediatric populations. In a study of 31 overweight and obese adolescents (77% female), Simon and colleagues demonstrated that greater social jet lag was associated with reduced insulin sensitivity. The authors also reported shorter weekday sleep duration among individuals with an evening chronotype, as well as a positive association between insulin resistance and a wider phase angle between bedtime and melatonin onset, indicative of delayed sleep–wake phase [80]. In another cohort of 59 obese adolescent girls with polycystic ovary syndrome (PCOS), the same group identified a significant association between morning circadian misalignment and insulin resistance, compared with 33 age-matched obese controls without PCOS. Morning circadian misalignment was quantified as the interval between melatonin offset time and clock time. Notably, all participants were screened for sleep-disordered breathing, which was excluded as a confounding factor [81].

Extending these observations to earlier developmental stages, the impact of sleep deprivation is particularly pronounced in early life, a critical period for metabolic programming and long-term health trajectories. Epidemiological evidence indicates that insufficient sleep in childhood is strongly associated with increased obesity risk. For instance, Guo et al. (2021) reported a 35–41% higher likelihood of obesity among Chinese children and adolescents aged 6–17 years with shorter sleep durations [82]. Notably, this relationship emerges even earlier in life; Lumeng et al. (2007) demonstrated a similar association in children as young as 2–7 years, underscoring the early onset of this risk [83]. These findings raise important concerns regarding behavioral and environmental determinants of sleep in pediatric populations. Inadequate prioritization of sleep by caregivers may inadvertently foster unhealthy lifestyle patterns from a young age, predisposing children to sustained metabolic dysregulation. Given the well-established interplay among sleep, neuroendocrine regulation, and energy balance, early-life sleep curtailment may represent a critical, modifiable risk factor that contributes to the lifelong burden of obesity and its associated cardiometabolic complications [84].

In addition to its effects on glucose metabolism and hormonal regulation, sleep deprivation also impairs fat utilization. In 2010, Nedeltcheva et al. examined the impact of sleep restriction on the efficacy of a hypocaloric diet among overweight individuals seeking a leaner body appearance [85]. Participants were assigned to 2 sleep conditions (5.5 h vs. 8.5 h in bed) for 2 weeks each, with a washout period in between. Although comparable weight loss was observed under both conditions, the composition of weight loss differed markedly. Under adequate sleep conditions, > 50% of the weight loss was attributable to reduction in adipose tissue. In contrast, during sleep restriction, over 60% of weight loss was attributable to lean tissue rather than fat [85]. These findings suggest that insufficient sleep impairs fat oxidation and shifts energy utilization away from lipid stores, thereby promoting the preservation of adipose tissue at the expense of lean body mass. Consequently, sleep deprivation may compromise the metabolic benefits of caloric restriction and hinder improvements in body composition.

Taken together, the previous findings indicate that the global obesity epidemic cannot be attributed to a single causal pathway, and sleep deprivation is no exception. While increased food consumption, larger meal portions, elevated caloric intake, and reduced physical activity remain key contributors, these factors alone are insufficient to account for the current magnitude of obesity prevalence [86]. Rather, a broader, multifactorial framework is required. In this context, a substantial and growing body of evidence has established a robust association between sleep curtailment and obesity risk. This relationship has been consistently demonstrated across epidemiological studies and contributes to the parallel rise of two major public health challenges, with significant implications for morbidity and mortality. Notably, longitudinal population data over the past 5 decades reveal a striking temporal convergence whereby declining sleep duration mirrors the upward trajectory of obesity rates. Such synchronized trends further reinforce the role of insufficient sleep as a critical yet often underappreciated determinant within the complex pathophysiology of obesity.

From a systems perspective, insufficient sleep, now prevalent in modern populations, induces a coordinated disruption of endocrine, neural, and behavioral pathways governing energy balance. Alterations in key appetite-regulating hormones (namely leptin, ghrelin, and endocannabinoids) drive increased hunger and caloric intake, while concurrent impairments in reward processing and executive control bias food selection toward energy-dense options. These effects, coupled with microbiome alterations and reduced responsiveness to dietary interventions, are related to a sustained positive energy balance despite relatively unchanged energy expenditure. Over time, this integrated metabolic dysregulation contributes to the development of obesity, T2DM, and their associated morbidity and mortality.