To understand how sleep is related to body weight, we first need to learn about a few important hormones that serve as messengers between these important physiological parameters.

The Hormones

Leptin

Leptin is a hormone predominantly made by adipose tissue (fat) with the primary function of fat store regulation. The word leptin comes from the Greek word “leptos”, meaning thin. Leptin regulates energy balance by inhibiting hunger and inducing satiety [1].

Ghrelin

Ghrelin is an orexigenic (appetite stimulating) hormone primarily produced in the stomach. The name ghrelin is derived from “ghre”, which means grow, and “relin”, which means release. It has stimulatory effects on growth hormone secretion, food intake, and fat deposition, thus is commonly referred to as the “hunger hormone”. Ghrelin plays an important role in glucose homeostasis [2,3]

Insulin

Insulin is a hormone produced by beta cells in the pancreas. It plays an important role in the regulation of carbohydrates, fats and protein metabolism by promoting the uptake of glucose by cells in the liver, skeletal muscles and adipose tissues.

Melatonin

Melatonin is the major circadian mediator of photoperiodic information to the central nervous system (Fig. 1). The daily circadian increase in melatonin secretion coincides with sleep episodes (Fig. 2).

Figure 1. When eyes receive light from the sun, the pineal gland’s production of melatonin is inhibited which keeps the human awake. When the eyes do not receive light, melatonin is produced in the pineal gland and the human becomes sleepy. (Source)

Figure 2. Phase relationship between the circadian rhythms of sleep and plasma melatonin. [4]

In correlation with the rise in endogenous melatonin levels in the evening, thermoregulation cascade occurs with decreased heat production and increased heat loss. The latter seems to be achieved through the melatonin signal timing the rise in blood flow in distal skin, suggesting melatonin’s role in thermoregulation [5].

Melatonin is also a key regulator of glucose homeostasis and energy metabolism. Not only a “sleep hormone”, melatonin is also involved in three major processes in energy balance: food intake, energy storage, and energy expenditure [6].

Melatonin, Glucose Metabolism and Energy Regulation

Melatonin and Energy Expenditure

Various animal experiments found melatonin playing a role in energy expenditure by shifting towards brown adipose tissue and increasing thermogenesis in mammals [7,8]. It is speculated that the same mechanism may apply to the human.

Melatonin and Insulin Resistance

A large number of animal studies found that abolishing melatonin levels produces glucose intolerance and insulin resistance [9].

Animal studies often use high-fat diet to induce abnormal metabolic conditions and obesity in mice. Interestingly, reintroducing melatonin from external sources into the body restored metabolic parameters to normal levels [10]. Another study demonstrated that daily melatonin administration decreased the bodyweight gain of these high-fat diet fed mice by 54% [11]. Xu, et al. [12] found in an animal study that melatonin was capable of modulating gut bacteriota back to healthy levels and provided beneficial effects against obesity, insulin resistance, and low-grade inflammation in high-fat diet fed mice.

It should be noted that so far most of these were animal studies, especially studies conducted on rodents, which are nocturnal animals. Differences may exist in each species and more human studies are needed. What have been demonstrated in human subjects is that genetic variants in melatonin receptors have been associated with metabolic disorders such as type 2 diabetes, gestational diabetes mellitus, and obesity [9].

Interplay between melatonin and leptin

Melatonin plays a role in energy intake through its interplay with leptin [9]. Melatonin has been shown to drive the daily rhythm of plasma leptin. Animal experiments showed that long-term absence of circulating melatonin led to impairments in leptin signaling and leptin resistance within the hypothalamus [13]. Leptin resistance increases the expression of a number of orexigenic (appetite stimulating) genes, which results in long-term food intake and weight gain. Obese individuals demonstrates higher levels of circulating leptin due to leptin resistance. Interestingly, administration of exogenous melatonin prevented the negative effects [6,9].

Leptin, ghrelin, and sleep

In a cohort study involving 1,024 participants, short sleep duration has been associated with reduced leptin, elevated ghrelin, and increased body mass index (Fig. 3) [14], whereas other studies were unable to identify significant effects [15].

Figure 3. The relationship between BMI and average nightly sleep. [14]

In a myriad of studies, reduced sleep was found to increase food intake [15]. Studies that restricted sleep indicate some weight gain or less weight loss compared to control in three out of the four studies, but no significant effect overall [15]. These studies were however, limited by small sample sizes.

In a cross-sectional study involving 133,608 subjects (44,930 men, 88,678 women) during a study from 2004-2013, individuals having less than 6 hours of sleep was associated with elevated waist circumference among both men and women and with metabolic syndromes among men. Greater than 10 hours of sleep was also associated with negative metabolic responses [16].

The circadian rhythmicity of these hormones could explain the increased prevalence of metabolic disorders in shift workers [17].

Sleep and Energy Balance

There are many more hormones involved in the regulation of human metabolisms, such as glucagon, epinephrine, norepinephrine, cortisol, adiponectin, peptide YY, neuropeptide Y, etc. The interplay among these hormones and their influences on/by the peripheral/central circadian clocks are incredibly complex and intricate, and have not been fully elucidated.

What we do know is that the interplay between sleep, melatonin, and the various appetite hormones and metabolic hormones indicate links between sleep regulation and energy regulation, and that taking care of the sleep should be part of any weight-loss program. Sleep deficiency can also negatively affect energy balance in the following two ways: 

1. When one feels chronically tired, one may exercise less and burn fewer calories [18].
2. Sleep loss can affect impulse control, causing one to make poorer decisions about things like food and drinks [19].

Sleep loss can snowball into a big problem if not addressed early.

Sleep and Food Timing

Since we now know that appetite hormones and sleep hormones are intricately linked in the net of central and peripheral biological clocks, what advice can we take about food timing to facilitate sleep? It was found that high glycemic meal within 4 hours of bed time may improve sleep onset latency (the time taken to fall asleep) compared with a low glycemic meal. Consuming a high protein diet, avoiding high fat intake, and taking in around 1 gram of tryptophan (the amount found in 284 g of turkey) may also improve sleep onset and quality [20]. Timing is critical. A high glycemic meal 1 hour before bed has been shown to disturb sleep [21]. Practice good sleep hygiene such as sleep at regular timing, reduce blue light and stimulating activities a couple hours before your sleep time, reduce your room temperature by 1-3 degrees C, and keep the room dark while you are sleeping.

References

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[2] Pradhan, G., Samson, S.L., and Sun, Y. (2013). Ghrelin: much more than a hunger hormone. Current Opinion in Clinical Nutrition and Metabolic Care 16, 619–624.

[3] Khatib, N. (2014). Ghrelin: Ghrelin as a Regulatory Peptide in Growth Hormone Secretion. JCDR.

[4] Cajochen, C., Kräuchi, K., and Wirz-Justice, A. (2003). Role of Melatonin in the Regulation of Human Circadian Rhythms and Sleep: Melatonin, sleep and circadian rhythms. Journal of Neuroendocrinology 15, 432–437.

[5] Kräuchi, K., Cajochen, C., Werth, E., and Wirz-Justice, A. (1999). Warm feet promote the rapid onset of sleep. Nature 401, 36–37.

[6] Buonfiglio, D., Parthimos, R., Dantas, R., Cerqueira Silva, R., Gomes, G., Andrade-Silva, J., Ramos-Lobo, A., Amaral, F.G., Matos, R., Sinésio, J., et al. (2018). Melatonin Absence Leads to Long-Term Leptin Resistance and Overweight in Rats. Front. Endocrinol. 9, 122.

[7] Fernández Vázquez, G., Reiter, R.J., and Agil, A. (2018). Melatonin increases brown adipose tissue mass and function in Zücker diabetic fatty rats: implications for obesity control. J Pineal Res 64, e12472

[8] Tan, D.-X., Manchester, L.C., Fuentes-Broto, L., Paredes, S.D., and Reiter, R.J. (2011). Significance and application of melatonin in the regulation of brown adipose tissue metabolism: relation to human obesity: Melatonin and brown adipose tissue. Obesity Reviews 12, 167–188.

[9] Owino, S., Buonfiglio, D.D.C., Tchio, C., and Tosini, G. (2019). Melatonin Signaling a Key Regulator of Glucose Homeostasis and Energy Metabolism. Front. Endocrinol. 10, 488.

[10] Sartori, C., Dessen, P., Mathieu, C., Monney, A., Bloch, J., Nicod, P., Scherrer, U., and Duplain, H. (2009). Melatonin Improves Glucose Homeostasis and Endothelial Vascular Function in High-Fat Diet-Fed Insulin-Resistant Mice. Endocrinology 150, 5311–5317.

[11] Prunet-Marcassus, B., Desbazeille, M., Bros, A., Louche, K., Delagrange, P., Renard, P., Casteilla, L., and Pénicaud, L. (2003). Melatonin Reduces Body Weight Gain in Sprague Dawley Rats with Diet-Induced Obesity. Endocrinology 144, 5347–5352.

[12] Xu, P., Wang, J., Hong, F., Wang, S., Jin, X., Xue, T., Jia, L., and Zhai, Y. (2017). Melatonin prevents obesity through modulation of gut microbiota in mice. J. Pineal Res. 62, e12399.

[13] Chakir, I., Dumont, S., Pévet, P., Ouarour, A., Challet, E., and Vuillez, P. (2015). Pineal melatonin is a circadian time-giver for leptin rhythm in Syrian hamsters. Front. Neurosci. 9.

[14] Taheri, S., Lin, L., Austin, D., Young, T., and Mignot, E. (2004). Short Sleep Duration Is Associated with Reduced Leptin, Elevated Ghrelin, and Increased Body Mass Index. PLoS Med 1, e62.

[15] Capers, P.L., Fobian, A.D., Kaiser, K.A., Borah, R., and Allison, D.B. (2015). A systematic review and meta-analysis of randomized controlled trials of the impact of sleep duration on adiposity and components of energy balance: Sleep and energy balance meta-analysis. Obesity Reviews 16, 771–782.

[16] Kim, C.E., Shin, S., Lee, H.-W., Lim, J., Lee, J., Shin, A., and Kang, D. (2018). Association between sleep duration and metabolic syndrome: a cross-sectional study. BMC Public Health 18, 720.

[17] Shea, S.A., Hilton, M.F., Orlova, C., Ayers, R.T., and Mantzoros, C.S. (2005). Independent Circadian and Sleep/Wake Regulation of Adipokines and Glucose in Humans. The Journal of Clinical Endocrinology & Metabolism 90, 2537–2544

[18] Schmid, S.M., Hallschmid, M., Jauch-Chara, K., Wilms, B., Benedict, C., Lehnert, H., Born, J., and Schultes, B. (2009). Short-term sleep loss decreases physical activity under free-living conditions but does not increase food intake under time-deprived laboratory conditions in healthy men. The American Journal of Clinical Nutrition 90, 1476–1482.

[19] Greer, S.M., Goldstein, A.N., and Walker, M.P. (2013). The impact of sleep deprivation on food desire in the human brain. Nat Commun 4, 2259.

[20] Domitrovich, JW. Wildland Firefighter Health and Safety Report #14. United States Forest Service: MTDC, 2011.

[21] Heil, DP. Estimating energy expenditure in wildland fire fighters using a physical activity monitor. Appl Ergonomics 33:405-413, 2002.)