Interactions between sleep, stress, and metabolism: From physiological to pathological conditions

In the paper Interactions between Sleep, Stress, and Metabolism: From Physiological to Pathological Conditions, Hirotsu et al. explore the complex relationships between sleep, stress, and metabolic health. The authors explain how poor sleep quality and stress, through the activation of the hypothalamic-pituitary-adrenal (HPA) axis, lead to hormonal imbalances, particularly with cortisol. These imbalances disrupt the body’s ability to regulate glucose and fat, contributing to the rising prevalence of obesity, type 2 diabetes, and other metabolic disorders. The paper emphasizes the importance of understanding these interactions to identify potential treatments and preventive strategies for managing metabolic dysfunction in modern society.

People are experiencing more stress and getting less sleep, which is common in modern societies. As a result, we are seeing an increase in metabolic issues like obesity and diabetes. These three factors—sleep, stress, and metabolism—are deeply connected. When you don't get enough sleep or deal with too much stress, your body's normal functions can be thrown off balance, which leads to problems with how your body processes food and stores energy.

The relationship between sleep and metabolism is controlled by a system in the body called the hypothalamic-pituitary-adrenal (HPA) axis. The HPA axis is responsible for releasing cortisol, the "stress hormone." This research explains how disruptions to sleep and increases in stress can lead to metabolic problems. Understanding these connections can help us find better ways to prevent and treat conditions like obesity and diabetes.

The research gathered and analyzed human and animal studies to explore how sleep, stress, and metabolism interact. The focus was on understanding the role of the HPA axis, which connects the brain to stress and metabolic regulation. When activated, the HPA axis releases cortisol, disturbing sleep patterns and increasing stress levels.

The review examined studies on sleep deprivation, which is common today, especially in people who work long hours or experience sleep disorders like insomnia and obstructive sleep apnea (OSA). Both of these conditions were analyzed to understand how they contribute to stress and metabolic changes. By comparing these studies, the research highlights how poor sleep directly impacts hormone levels, which in turn affects how the body uses and stores energy.

For example, in people with insomnia, evening cortisol levels remain high, making it difficult to fall asleep and stay asleep. Meanwhile, in OSA patients, repeated pauses in breathing during the night lead to sleep fragmentation and affect hormone levels that control hunger and stress.

Sleep and stress work together in a cycle that can be hard to break. Stress triggers the release of cortisol, a hormone that wakes us up and makes us alert. This is helpful in small amounts, but cortisol stays elevated when stress lasts a long time, which disrupts sleep.

The research notes that "cortisol levels increase after sleep onset and continue to rise into the waking hours." Lack of sleep, in turn, makes the HPA axis more active, further increasing stress levels and making sleep more difficult. This creates a vicious cycle where sleep problems and stress feed off each other.

The stress caused by poor sleep and the activation of the HPA axis seriously affect metabolism. High cortisol levels lead to increased glucose and insulin while lowering adiponectin, a hormone that helps break down fats. The research points out that this can contribute to weight gain and increase the risk of type 2 diabetes: "Sleep deprivation is related to the elevation of cortisol, reflecting impairment of HPA axis regulation, and resulting in glucocorticoid overload, which can lead to large deleterious effects on the body."

Additionally, sleep loss affects hormones that control hunger. Leptin, which suppresses appetite, decreases, while ghrelin, which increases hunger, rises. This combination leads to overeating, particularly cravings for high-calorie foods. For example, after just two nights of restricted sleep, young men showed a "28% increase in ghrelin and an 18% reduction in leptin."

Sleep disorders like insomnia and obstructive sleep apnea (OSA) are common conditions that also impact metabolism. Insomnia, characterized by difficulty falling or staying asleep, leads to higher evening cortisol levels. This disrupts the body's natural rhythm and prevents restful sleep. As a result, people living with insomnia often experience daytime fatigue and higher stress levels, which in turn affect their metabolic health.

Obstructive sleep apnea (OSA) is another common disorder in which breathing repeatedly stops and starts during sleep, leading to fragmented rest. The connection between OSA and cortisol is complex. While some studies have shown that OSA patients have elevated cortisol levels, others report no significant changes. However, what is clear is that "up to 86% of obese patients with type 2 diabetes also have OSA," highlighting a strong link between the two conditions.

Glucocorticoids like cortisol have a direct impact on sleep and metabolism. High cortisol levels keep people awake and reduce deep, restorative sleep. This makes it harder for the body to recover from stress and manage blood sugar levels properly. Excess cortisol also stores fat, especially in the belly area, which increases the risk of obesity.

The review explains that "chronic exposure to excess glucocorticoids, such as occurs during diseases like Cushing's syndrome, leads to weight gain and metabolic syndrome ." People with high cortisol levels often show signs of disrupted sleep, including shorter REM sleep (the dreaming stage) and more time spent awake.

The close relationship between sleep, stress, and metabolism means that managing these factors can significantly improve health outcomes. The findings suggest that improving sleep quality and reducing stress can lower the risk of metabolic disorders like obesity and type 2 diabetes.

To address these issues, there are several strategies people can try:

• Practicing good sleep hygiene: This includes having a regular sleep schedule, creating a calm sleep environment, and avoiding caffeine or screens before bed.
• Treating sleep disorders: Conditions like insomnia and OSA should be properly diagnosed and treated with therapies such as cognitive behavioral therapy for insomnia (CBT-I) or continuous positive airway pressure (CPAP) for OSA.
• Nutritional adjustments: Aligning eating habits with the body's natural rhythms may also help. For example, eating regular meals and avoiding late-night snacks can support better sleep and metabolic health.
• 
  

The review also highlights promising research on new treatment approaches. One possible target is the enzyme 11β-HSD1, which plays a role in cortisol metabolism. Blocking this enzyme could help lower cortisol levels and reduce fat storage, offering a new way to treat obesity and other metabolic issues tied to poor sleep and high stress.

The relationship between sleep, stress, and metabolism has become more important than ever. Sleep deprivation and stress have a powerful impact on our bodies, increasing the risk of metabolic disorders like obesity and diabetes. Poor sleep and stress continuously activate the HPA axis, leading to higher cortisol levels, which in turn affect how we process food, store energy, and manage hunger.

To break this harmful cycle, it's essential to focus on getting enough good-quality sleep and effectively managing stress. Treatments like improving sleep hygiene, managing sleep disorders, and even targeting cortisol-related pathways in the body could help prevent metabolic problems before they start. By understanding how sleep, stress, and metabolism interact, we can take steps to improve overall health and reduce the risk of chronic diseases.