Dr. Sharma's Obesity Notes

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

You can now also follow me and post your comments on Facebook

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

According to the National Sleep Foundation’s 2007 Sleep in America poll, just published by Eileen Chasens and colleagues from the University of Pittsburgh in this month’s issue of Behavior and Sleep Medicine, almost 20% of community-dwelling women aged 40 to 60 years reported sleepiness that consistently interfered with daily life.

Perhaps not surprisingly, the sleepy subsample reported more symptoms of insomnia, restless legs syndrome, obstructive sleep apnea, depression and anxiety, as well as more problems with health-promoting behaviors, drowsy driving, job performance, household duties, and personal relationships.

Further analyses revealed that sleepiness along with depressive symptoms, medical comorbidities, obesity, and lower education were associated with poor self-rated health, whereas menopause status (pre-, peri- or post-) was not.

These results point to the high prevalence of daytime sleepiness in midlife women and suggest that addressing the underlying causes of poor sleep and sleep disruption may be an important measure to improve health in this population.

Obviously, what applies to the midlife women in this study may well also apply to women of other age groups as well as men - and of course our kids.

Perhaps we should all use the long weekend to get more sleep.

AMS
Edmonton, Alberta

p.s. You can now also follow me and post your comments on Facebook

Chasens ER, Twerski SR, Yang K, & Umlauf MG (2010). Sleepiness and health in midlife women: results of the National Sleep Foundation’s 2007 Sleep in America poll. Behavioral sleep medicine, 8 (3), 157-71 PMID: 20582759

Regular readers of these pages will recall previous articles on the discoveryof brown adipose tissue in adult humans.

Brown adipose tissue or BAT is specifically designed to turn calories into heat, thereby significantly affecting metabolic rate.

The current theory is that people who have more BAT, are more obesity resistant and can better handle excess calories. It is estimated that just 50 grams of BAT may help burn several hundred extra calories per day.

This discovery has spawned a huge interest into the functioning and regulation of BAT amongst obesity researchers and many are looking into possible ways of increasing the amount of BAT or of stimulating it to burn more calories.

An article by Tan and colleagues from the University of Texas, San Antonio, TX, released this week in Obesity Reviews, examines the evidence in support of the notion that melatonin, an endogenous peptide intimately linked to the biology of sleep, may play an important role in the regulation of BAT metabolism.

Secreted by the pineal gland at night, melatonin plays a key role in regulating the sleep-wake cycle and many other circadian rhythms in physiological functions like glucose homeostasis or body temperature. Importantly, both natural and artificial light can markedly suppress melatonin production.

In their articles, the authors quote a number of articles showing that in mammals, melatonin not only increases recruitment of brown adipocytes but also elevates their metabolic activity.

Based on these findings, the authors speculate that the hypertrophic effect and functional activation of BAT by melatonin, if also present in humans, may suggest a novel role for melatonin in managing obesity.

Perhaps more importantly, the authors note that the suppression of endogenous melatonin levels due to excessive light exposure after darkness through artificial light sources, may contribute to the obesity epidemic, as exposure to light at night has been shown to dramatically reduce endogenous melatonin production.

Perhaps it may well be this complex physiology linking BAT to melatonin that in part explains the important recent recognition that sleep deprivation may be a key factor in the obesity epidemic in both adults and children.

Perhaps lights out at 9.00 pm may not be such a bad weight management strategy after all?

AMS
Edmonton, Alberta

p.s. You can now also follow me and post your comments on Facebook

Tan DX, Manchester LC, Fuentes-Broto L, Paredes SD, & Reiter RJ (2010). Significance and application of melatonin in the regulation of brown adipose tissue metabolism: relation to human obesity. Obesity reviews : an official journal of the International Association for the Study of Obesity PMID: 20557470

As blogged before, overweight and obese patients frequently present with fibromyalgia, characterized by chronic pain, fatigue and depressed mood.

A paper by Akiko Okifuji from the University of Utah, Salt Lake City, just published in the Journal of Pain, examines the relationship between fibromyalgia and obesity in pain, function, mood, and sleep.

The study examines the impact of obesity on hyperalgesia, symptoms, physical abilities, and sleep in 215 fibromyalgia patients, who also underwent tender point examination, physical performance testing, and 7-day home sleep assessment.

Almost 50% of participants were obese and an additional 30% were overweight.

Obesity was positively related to greater tender point sensitivity, reduced physical strength and lower-body flexibility, shorter sleep duration, and greater restlessness during sleep.

The results confirmed that obesity is a prevalent comorbidity of fibromyalgia and the authors suggest that weight management may need to be incorporated into treatments.

In the paper, Okifuji and colleagues also discuss several potential mechanisms linking obesity to fibromyalgia including alterations in the endogenous opioid system, the endocrine system, and systemic inflammation, whereby adipose-tissue derived cytokines may enhance central sensitization.

Clinicians should be aware of the relationship between excess weight and fibromyalgia, which can often pose an important contributor to weight gain and a major barrier to weight management.

AMS
Edmonton, Alberta

Okifuji A, Donaldson GW, Barck L, & Fine PG (2010). Relationship Between Fibromyalgia and Obesity in Pain, Function, Mood, and Sleep. The journal of pain : official journal of the American Pain Society PMID: 20542742