In the last 50 years, the average self‐reported sleep duration in the United States has decreased by 1.5–2 hours in parallel with an increasing prevalence of obesity and diabetes. Epidemiological studies and meta‐analyses report a strong relationship between short or disturbed sleep, obesity, and abnormalities in glucose metabolism. This relationship is likely to be bidirectional and causal in nature, but many aspects remain to be elucidated. Sleep and the internal circadian clock influence a host of endocrine parameters. Sleep curtailment in humans alters multiple metabolic pathways, leading to more insulin resistance, possibly decreased energy expenditure, increased appetite, and immunological changes. On the other hand, psychological, endocrine, and anatomical abnormalities in individuals with obesity and/or diabetes can interfere with sleep duration and quality, thus creating a vicious cycle. In this review, we address mechanisms linking sleep with metabolism, highlight the need for studies conducted in real‐life settings, and explore therapeutic interventions to improve sleep, with a potential beneficial effect on obesity and its comorbidities.

BackgroundShort sleep duration and decreased sleep quality are emerging risk factors for obesity and its associated morbidities. Chronotype, an attribute that reflects individual preferences in the timing of sleep and other behaviors, is a continuum from morningness to eveningness. The importance of chronotype in relation to obesity is mostly unknown. Evening types tend to have unhealthy eating habits and suffer from psychological problems more frequently than Morning types, thus we hypothesized that eveningness may affect health parameters in a cohort of obese individuals reporting sleeping less than 6.5 hours per night.Methodology and Principal FindingsBaseline data from obese (BMI: 38.5±6.4 kg/m2) and short sleeping (5.8±0.8 h/night by actigraphy) participants (n = 119) of the Sleep Extension Study were analyzed (www.ClinicalTrials.gov, identifier NCT00261898). Assessments included the Horne and Ostberg Morningness-Eveningness questionnaire, a three-day dietary intake diary, a 14-day sleep diary, 14 days of actigraphy, and measurements of sleep apnea. Twenty-four hour urinary free cortisol, 24 h urinary norepinephrine and epinephrine levels, morning plasma ACTH and serum cortisol, fasting glucose and insulin, and lipid parameters were determined. Eveningness was associated with eating later in the day on both working and non-working days. Progression towards eveningness was associated with an increase in BMI, resting heart rate, food portion size, and a decrease in the number of eating occasions and HDL-cholesterol. Evening types had overtly higher 24 h urinary epinephrine and morning plasma ACTH levels, and higher morning resting heart rate than Morning types. In addition, Evening types more often had sleep apnea, independent of BMI or neck circumference.ConclusionsEveningness was associated with eating later and a tendency towards fewer and larger meals and lower HDL-cholesterol levels. In addition, Evening types had more sleep apnea and higher stress hormones. Thus, eveningness in obese, chronically sleep-deprived individuals compounds the cardiovascular risk associated with obesity.

Disturbances in the circadian system are associated with the development of type 2 diabetes mellitus. Here, we studied the direct contribution of the suprachiasmatic nucleus (SCN), the central pacemaker in the circadian system, in the development of insulin resistance. Exclusive bilateral SCN lesions in male C57Bl/6J mice, as verified by immunochemistry, showed a small but significant increase in body weight (+17%), which was accounted for by an increase in fat mass. In contrast, mice with collateral damage to the ventromedial hypothalamus and paraventricular nucleus showed severe obesity and insulin resistance. Mice with exclusive SCN ablation revealed a loss of circadian rhythm in activity, oxygen consumption, and food intake. Hyperinsulinemic–euglycemic clamp analysis 8 weeks after lesioning showed that the glucose infusion rate was significantly lower in SCN lesioned mice compared with sham-operated mice (−63%). Although insulin potently inhibited endogenous glucose production (−84%), this was greatly reduced in SCN lesioned mice (−7%), indicating severe hepatic insulin resistance. Our data show that SCN malfunctioning plays an important role in the disturbance of energy balance and suggest that an absence of central clock activity, in a genetically intact animal, may lead to the development of insulin resistance.

Disruption of circadian rhythmicity is associated with obesity and related disorders, including type 2 diabetes and cardiovascular disease. Specifically, prolonged artificial light exposure associates with obesity in humans, although the underlying mechanism is unclear. Here, we report that increasing the daily hours of light exposure increases body adiposity through attenuation of brown adipose tissue (BAT) activity, a major contributor of energy expenditure. Mice exposed to a prolonged day length of 16-and 24-h light, compared with regular 12-h light, showed increased adiposity without affecting food intake or locomotor activity. Mechanistically, we demonstrated that prolonged day length decreases sympathetic input into BAT and reduces β3-adrenergic intracellular signaling. Concomitantly, prolonging day length decreased the uptake of fatty acids from triglyceride-rich lipoproteins, as well as of glucose from plasma selectively by BAT. We conclude that impaired BAT activity is an important mediator in the association between disturbed circadian rhythm and adiposity, and anticipate that activation of BAT may overcome the adverse metabolic consequences of disturbed circadian rhythmicity. M odern world society is subjected to disturbances of circadian rhythms by shift work, sleep deprivation, and environmental light pollution. Importantly, the increasing prevalence of obesity is associated with a disrupted sleep-wake pattern in humans (1) and coincides with the availability of artificial light (2, 3). Additionally, a recent study revealed a relationship between exposure to light at night and obesity in a cross-sectional analysis of over 100,000 women (4). Light input is the most important cue for generation of circadian (∼24 h) rhythms by the master clock. Both in rodents and humans the master clock is situated in the suprachiasmatic nucleus (SCN) of the hypothalamus. The SCN is responsible for synchronization of peripheral clocks throughout the body, which is mediated by endocrine and neuronal signals (5). A causal role for a disturbed circadian rhythm in the development of obesity has been demonstrated by animal studies. Mice with genetically dysfunctional clock genes develop obesity and insulin resistance (6-9). Moreover, specific ablation of the SCN induces acute weight gain (10). These results indicate a crucial role for the SCN in the regulation of adiposity.Interestingly, we previously showed that prolonged light exposure only is sufficient to enhance weight gain in mice. Constant light disrupts the central circadian clock, evidenced by an immediate reduction in the circadian amplitude of SCN electrical activity. Moreover, constant light induces body weight gain and insulin resistance, even faster than high-fat diet, which was not caused by increased food intake or reduced locomotor activity (11). Therefore, disruption of the central biological clock likely induces weight gain by decreasing energy expenditure.Recently, it has been recognized that brown adipose tissue (BAT) importantly contributes to energy ...