From the Research
The relationship between orexin, leptin, cortisol, and melatonin is a complex interplay that regulates our sleep-wake cycle, appetite, and stress response throughout the day, with orexin peaking during wakefulness, leptin rising at night, cortisol following a distinct circadian rhythm, and melatonin working oppositely to cortisol. The most recent and highest quality study on this topic is from 2023 1, which explores the role of orexin in the regulation of REM sleep and appetite. According to this study, orexin should be considered essentially as a neurotransmitter inhibiting REM sleep and, to a much lesser extent, a wake promoting agent. Key points about the relationship between these hormones include:
- Orexin (also called hypocretin) peaks during wakefulness, promoting alertness and appetite, while decreasing as we approach sleep.
- Leptin, which signals satiety, typically rises at night to suppress appetite during sleep, with lower levels during the day when we need to eat, as supported by a study from 2012 2 that found serum leptin levels were increased during night.
- Cortisol follows a distinct circadian rhythm, with levels highest in the early morning to help us wake up and gradually declining throughout the day, reaching its lowest point around midnight.
- Melatonin works oppositely to cortisol, beginning to rise in the evening when light exposure decreases, peaking in the middle of the night to promote sleep, and then declining by morning. These hormones work together to coordinate our daily rhythms - when cortisol and orexin are high during the day, we feel alert and hungry, while evening increases in melatonin and leptin promote sleep and reduced appetite. Disruptions to this balance, such as from shift work, jet lag, or chronic stress, can affect sleep quality, appetite regulation, and overall metabolic health, as discussed in a study from 2004 3 that found sleep modulates a major component of the neuroendocrine control of appetite. Additionally, a study from 2022 4 highlights the importance of orexin in the central physiological regulation of sleep and wakefulness, and its potential therapeutic applications. Another study from 2011 5 examines the interaction of season, orexin, ghrelin, and leptin on melatonin secretion, and found that the responses of the pineal gland to these hormones depend on day length. Overall, understanding the intricate relationship between orexin, leptin, cortisol, and melatonin is vital for unraveling the complex mechanisms underlying sleep-wake patterns and metabolic control, as emphasized in the 2023 study 1.