Arya M. Sharma, MD

One of the recurring topics at the Obesity Summit was the importance of sleep in terms of its effects on ingestive behaviour, metabolism and other important parameters.

Now a study by Kelly Baron and colleagues from Northwestern University, Chicago, published in OBESITY, adds an additional dimension to this discussion, i.e. the importance of sleep timing.

As regular readers may recall, I have previously posted the results of animal studies demonstrating the impact of timing of feeding in energy homeostasis - feeding mice during the day (their night) leads to more weight gain than feeding them the same amount of calories during the night (their day).

In their study, Baron and colleagues now evaluated the role of sleep timing in dietary patterns and BMI in 52 (25 females) volunteers who completed 7 days of wrist actigraphy and food logs.

Participants were classified as having normal sleep times if midpoint of sleep was between 1:00 am to 5:29 am, and participants were classified as having late sleep times if midpoint of sleep was 5:30 am or later, which is past the 50th percentile of sleep times in the population (4:00 am)

Late sleepers also consumed more calories at dinner and after 8:00 PM, had higher fast food, full-calorie soda and lower fruit and vegetable consumption.

Not surprisingly, therefore, higher BMI was associated with shorter sleep duration, later sleep timing, caloric consumption after 8:00 PM, and fast food meals.

In addition, calories consumed after 8:00 PM predicted BMI after controlling for sleep timing and duration, suggesting that eating after 8:00 PM may increase the risk of obesity, independent of sleep timing and duration.

If these associations are indeed causally related (which will need to be demonstrated in intervention trials), two important clinical recommendations could emerge:

Get at least half your night’s sleep before 5.30 am and get your day’s supply of calories before 8.00 pm.

Wonder if anyone has experienced changes in their eating behaviour and/or weight with changes in sleep timing or not eating after 8.00 pm.

As for me, I probably just need to figure out which time zone actually counts for me - after all, it is always before 8.00 pm somewhere.

AMS
Edmonton, Alberta

Baron KG, Reid KJ, Kern AS, & Zee PC (2011). Role of Sleep Timing in Caloric Intake and BMI. Obesity (Silver Spring, Md.) PMID: 21527892

Regular readers of these pages should be well aware of the mounting evidence that points to lack of sleep as an important driver of the obesity epidemic. Not only does lack of sleep increase cravings for “junk” foods, reduce energy levels and physical activity, but it also negatively affects metabolism.

In addition, it now seems that simply disrupting the natural (24-h) circadian rhythm and sleep-wake cycle (as seen in shift workers, young parents, and people who frequently travel across time zones) may also promote weight gain.

This phenomenon was now carefully examined by Ilia Karatsoreos and colleagues from Rockefeller University, NY, in a paper just published in the Proceedings of the National Academy of Science (USA).

As the authors point out:

“Over the past 100 y, especially with the advent of electric lighting, modern society has resulted in a round-the-clock lifestyle, in which natural connections between rest/activity cycles and environmental light/dark cycles have been degraded or even broken.”

To examine the effects of this disruption of circadian rhythm in mammals, the researchers exposed healthy mice to 20-h light/dark cycles, incongruous with their endogenous ∼24-h circadian period.

Over time, this disruption of circadian rhythm resulted in accelerated weight gain and obesity, as well as changes in metabolic hormones.

In addition, the researchers found marked in changes in the brains of these animals including loss of dendritic length and decreased complexity of neurons in brain regions important for complex executive functions and emotional control.

Consistent with these changes in brain architecture, disrupted animals showed decreased cognitive flexibility and changes in emotionality in experiments designed to test these functions.

These findings certainly support the notion that chronically disrupting the natural (24-h) circadian rhythm in mammals can lead to substantial changes in behaviour and alterations in metabolism that would promote weight gain.

Certainly further reason to make a careful evaluation of sleep history an essential part of any clinical assessment for weight gain and obesity.

AMS
Edmonton, Alberta

Karatsoreos IN, Bhagat S, Bloss EB, Morrison JH, & McEwen BS (2011). Disruption of circadian clocks has ramifications for metabolism, brain, and behavior. Proceedings of the National Academy of Sciences of the United States of America PMID: 21220317

Regular readers of these pages will recall numerous posts on the profound effect of sleep deprivation on appetite and metabolism - a factor, believed by many, to be a major driver of the obesity epidemic (and not just in kids!).

Although epidemiological studies on sleep leave much to be desired both in quality and representativeness, current estimates suggest that we may be sleeping around two hours less than in the 60s.

Add to this the increase in night work, extended exposure to artificial light, and a increased eating in the late evening and night hours, and it is not hard to see how these changes would have affected our natural biology.

Enough reason for last month’s issue of Best Practices & Research Endocrinology and Metabolism to be entirely dedicated to the topic of Sleep and Metabolism.

As pointed out in the preface by Eve van Cauter and David Ehrmann from the University of Chicago, independent observations linking metabolism, sleep and circadian function include the idenfication of the orexin system which links the control of wakefulness with eating behavior, the identification of the circadian ‘Clock’ gene as conferring an increased risk of obesity and diabetes and the “sleep debt study” which showed that short term sleep restriction in healthy young adults results in decreased glucose tolerance (see previous blog entries on all of these landmark studies).

The special issue attempts to provide a comprehensive overview of this exciting field with contributions spanning from the molecular circuitry of hypothalamic pathways linking sleep and metabolism to the clinical relevance of sleep for nocturnal hypoglycemia in diabetic patients.

Readers may particularly be interested in the following articles in this issue:

Role of sleep duration in the regulation of glucose metabolism and appetite (Lisa Morselli et al.)

Sleep duration and cardiometabolic risk: A review of the epidemiologic evidence (Kristen L. Knutson)

Bariatric surgery and its impact on sleep architecture, sleep-disordered breathing, and metabolism (Silvana Pannain & Babak Mokhlesi)

The impact of sleep disturbances on adipocyte function and lipid metabolism (Josiane Broussard & Matthew J. Brady)

Sleep loss and inflammation (Janet M. Mullington, et al.)

Circadian disruption and metabolic disease: Findings from animal models (Deanna Marie Arble, et al.)

Sleep and the response to hypoglycaemia (Kamila Jauch-Chara & Bernd Schultes)

Sleep and metabolism: Role of hypothalamic neuronal circuitry (Asya Rolls, et. al.)

New evidence for a role of melatonin in glucose regulation (Elmar Peschke & Eckhard Mühlbauer)

Metabolic consequences of intermittent hypoxia: Relevance to obstructive sleep apnea (Luciano F. Drager, et al.)

I can only concur with the hopes of the editors that,

“… this volume will offer a thought provoking overview of this new area of investigation and inspire novel lines of research on the intriguing links between sleep, circadian function and metabolism and their impact on the health and well-being of billions of individuals in modern society.”

AMS
Acapulco, Mexico

Van Cauter E, & Ehrmann DA (2010). Preface. Best practice & research. Clinical endocrinology & metabolism, 24 (5) PMID: 21112018

Regular readers will recall the many posts on the issue of intra-uterine epigenetic programming, that is now believed by many to be one of the key drivers of the childhood obesity epidemic.

As more and more human and experimental evidence for this hypothesis accumulates, it is becoming increasingly evident that the intra-uterine environment may play a central role in determining the future risk of obesity in offspring (even much later in life).

This notion is further supported by an interesting study by Ricardo Orozco-Solís and colleagues from the Université de Nantes, France, published in the latest issue of PLoS One, showing that in rats, maternal nutrition during pregnancy is linked to long-lasting changes in nutrient sensing and energy homeostasis in the hypothalamus (the brain centre that regulates eating behaviours).

In this study, the researchers analyzed the profile of the hypothalamus transcriptome (the sum of all genes expressed as RNAs) in 180 days-old rats born to dams fed either a control (200 g/kg) or a low-protein (80 g/kg) diet through pregnancy and lactation.

From the almost 30,000 examined genes, around 700 were up-regulated and 300 down-regulated by early protein restriction.

Most interestingly, the researchers found that perinatal protein restriction permanently altered the expression of two gene clusters regulating a large number of common cellular processes.

While the first gene cluster includes several gate keeper genes regulating insulin signaling and nutrient sensing, the second cluster represents a functional network of nuclear receptors and co-regulators of transcription involved in the detection and use of lipid nutrients as fuel. This network also links temporal and nutritional cues to metabolism through their tight interaction with the circadian clock (in this context readers may recall the recent posts on the link between sleep and obesity).

As pointed out by the authors, these findings clearly show that (protein-) malnutrition during pregnancy and lactation may play a key role in epigenetically programming hypothalamic circuits regulating energy homeostasis.

As blogged before, the key to preventing childhood obesity may well lie in ensuring maternal nutrition and healthy body weights - once born, as with the proverbial horses, the kids may be out of the barn!

AMS
Hamilton, Ontario

Orozco-Solís R, Matos RJ, Guzmán-Quevedo O, Lopes de Souza S, Bihouée A, Houlgatte R, Manhães de Castro R, & Bolaños-Jiménez F (2010). Nutritional programming in the rat is linked to long-lasting changes in nutrient sensing and energy homeostasis in the hypothalamus. PloS one, 5 (10) PMID: 20975839

Regular readers will recall the many previous posts on the relationship between lack of sleep and weight gain. Now new evidence shows that lack of adequate sleep may be even more detrimental in anyone trying to lose weight.

In a study published in a recent issue of the Annals of Internal Medicine, Arlet Nedeltcheva and colleagues from the University of Chicago, tested the hypothesis that lack of sufficient sleep adversely affects the neuroendocrine response and metabolic effects of caloric restriction.

In a complicated randomised, 2-period, 2-condition crossover study, 10 overweight nonsmoking adults (3 women and 7 men) with a mean age of 41 years and a BMI around 27, were subjected to 14 days of moderate caloric restriction with 8.5 or 5.5 hours of nighttime sleep in a sleep laboratory.

Despite the same amount of caloric restriction, sleep deprivations resulted in 55% less fat loss and alarmingly increased the loss of fat-free mass (muscle) by almost 60%.

Sleep deprivation was also associated with increased hunger and reduced fat oxidation.

The authors conclude that adequate sleep is important to prevent the loss of fat-free mass during weight loss.

As a corollary to this, we can perhaps also conclude that trying to lose weight during times of sleep deprivation may be counterproductive in that it is more likely to lead to loss of lean tissue than get rid of the unwanted fat.

I have often advised my time-pressed patients that if they had to chose between 60 mins of exercise and 60 mins of sleep to go for the sleep. This is particularly true, as we know that exercise further increases the need for sleep thereby, making the degree of sleep deprivation, which many of my patients already face, even worse.

I propose that a careful sleep history (if not a formal sleep study) and sleep counseling should be part of every bariatric assessment and weight management plan.

AMS
Montreal, QC

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Nedeltcheva AV, Kilkus JM, Imperial J, Schoeller DA, & Penev PD (2010). Insufficient sleep undermines dietary efforts to reduce adiposity. Annals of internal medicine, 153 (7), 435-41 PMID: 20921542