Christmas food for thought: the gains and pains of laughter

As Christmas approaches like a freight train I, like many, scramble to buy last minute gifts and prepare myself to gorge on feasts and booze and laughter(?) – all part of a joyous(??) family gathering. In last effort to procrastinate until the very end, I present to you this short series of posts on various and totally random holiday-related themes. Enjoy!

Sings: Petri dish sterilizing near an open fire, lab rats nipping on my shoe, data woes cried by grad students, and PIs dressed like You-Know-Who! Ok, this might’ve gotten a laugh out of grad students. Anyone? I’ll show myself out.

Laughter permeates holiday gatherings. Dubbed “grooming at a distance”, laughter is thought to establish and maintain bonds between individual primates of all sorts. Like yawning, the mere sound of laughter often triggers giggling fits in others in a contagion-like manner. Within four-tenths of a second after exposure, electrical activity spreads out through areas involved in cognition, emotion, sensation and movement; this triggers facial contortions, spasmodic breathing and bodily convulsions as we involuntarily emit a series of curious vocalizations, ready to infect another.

Collapsing in a quivering heap, we are left under-the-influence of a deluge of a neuroendocrine cocktail. The amount of epinerphrine, a hormone in the fight-or-flight response plummets, while dopac, a major metabolite of dopamine, shoots up. Laughter also triggers the release of pain-relieving endorphins and growth- and metabolism-boosting growth hormone, which together with other chemicals form somewhat of a panacea for the mind and body. As Robert Burton once astutely wrote in 1621, “Mirth…prorogues life, whets the wit, makes the body young, lively and fit for any manner of employment.”

So where’s the evidence?

British Medical Journal produced a snicker-inducing, tongue-in-cheek report that synthesized findings from 785 papers on the health benefits of laughter. To round things up, they threw in harmful effects for good measure, while discarding papers written by authors with “Laugh” in their last name which where nonetheless “not particularly amusing”. Here’s what they found.

In terms of the psyche, laughter increased tolerance to pain in the lab, but hospital clowns did not reduce distress in children going through minor surgery to any observable extent. Humorous movies had minimal success on serious mental illnesses like schizophrenia, and group-based humor therapy did not particularly benefit late-onset depression in Alzheimer’s disease, though there was some improvement in patient morale and mood. Laughter was associated with life-long satisfaction, but there’s no evidence that one causes the other either way.

More mirthful news comes from laughter’s effect on the body. A 20min funny movie acutely reduced the stiffness of blood vessels and made them more limbre. A sense of humour lowers your risk of heart attack and improved lung function in those with chronic obstructive pulmonary disease, an illness that makes it difficult to breathe. In the latter case the credit goes to hospital clowns, whom apparently until the year of study (2008) were still regarded by some brave souls as non-terrifying entities.

Laughter had no consistent effects on immune functions such as natural killer cells, but sometimes aided the surgical removal of a pouch of pus by bursting it through laughter-generated muscle contractions. Laughter also benefits metabolism: compared to a monotonous lecture that drooled forever on, a comedy show helped control blood sugar levels after a meal. A 15min-bout of genuine laughter burns up to 40 calories, so battling the average 6000-calorie Christmas dinner would requires 37.5hrs of merriment to burn off. Better get those jokes ready.

Finally, if you’re trying to get pregnant through in vitro fertilization (test-tube baby), perhaps consider hiring a clown dressed like a chef de cuisine. In one study, such a clown entertained 110 would-be mothers after embryo transfer for 12-15 minutes with saucy jokes and magic tricks, “a recipe of success” that led to ~16% increase in pregnancy rate compared to the 109 non-clowned controls, adding another win for medicinal clowning.

Unfortunately laughter is not without its pains. Laughter weakens resolve and promotes your preference for certain brands, so keep a skeptic eye on that joke-cracking salesman. A hearty guffaw can cause temporary loss of consciousness, perhaps due to the sudden increase in pressure in the chest cavity that triggers a neural response. Laughing can screw up the electrical activity in the heart causing it to pump irregularly, to the point of cardiac arrest or rupture, giving “dying of laughter” a more sinister undertone.

Laughter can lead to abnormal collection of gas between the lung and chest wall or engorgement of air sacs of the lungs, resulting in labored breathing. The sharp intake of air to initiate laughter can promote inhaling foreign objects, causing you to choke on a small piece of turkey, while frequent exhaling disseminates infection. Laughter may also wreck havoc on your alimentary canal, dislocating the jaw or puncturing the esophagus (your “food-tube”), so maybe eat first and laugh later. You might also want a clear line to the wash(bath)room. Laughter can cause incontinence stemming from involuntary contractions of bladder muscles, which surprisingly may be counteracted by Ritalin.

And finally, uproarious laughter may not be so funny to your brain. Cataplexy, a condition where a person suddenly looses muscle tone, can be triggered by laughter and other salient stimuli, leaving you unceremoniously collapsed under the Christmas tree. That is, unless only one side of you is affected. In one documented case, laughter triggered cataplexy only on the right side of a patient’s body, leaving her presumably capable of continuing laughing on the left side of her face.

Laughter and other pleasurable things may precipitate headaches in the unfortunate, sometimes due to sacs of jello-like material in the third ventricle, a fluid-filled compartment in the brain. Laughter may also be no laughing matter to people with patent foramen ovale (PFO), whom have a hole in the heart that should’ve closed after birth but didn’t. Take this case for example: after 3 minutes of roaring laughter, a PFO patient lost her words (literally) and had a stroke.

This report from BJM obviously shows that laughter is not all beneficial, but it overall carries a low risk of harm in the general population. In terms of cost-benefit analysis a good laugh is still beneficial. Yet, as always, more research calls. As the authors put it:

“It remains to be seen whether, for example, sick jokes make you ill, if dry wit causes dehydration, or jokes in bad taste cause dysgeusia (note: distortion of the sense of taste), and whether our views on comedians stand up to further scrutiny.”
R E Ferner, & J K Aronson (2013). Laughter and MIRTH (Methodical Investigation of Risibility, Therapeutic and Harmful): narrative synthesis BJM DOI: 10.1136/bmj.f7274

#SfN13 Stressed out mice turn to carbs for comfort food

Poster ZZ3 Ghrelin protects against stress by promoting the consumption of carbohydrates.T. Rodrigues. Z. Patterson. A. Abizaid. Carleton University, Ottawa, ON, Canada

In this world nothing can be said to be certain, except death and taxes.– Benjamin Franklin

Personally, I’d add stress to that.

There’s no question that chronic stress is a killer. Handled badly, stress can lead to anxiety, memory impairments, cardiovascular disease and sleep disorders. We all have our own strategies for coping with stress, some healthier than others. Me? I turn to food.


Cavities galore or stress relief? Source: 

Apparently, so do bullied mice. Mice are social creatures; when housed together, larger and meaner ones will quickly assert dominance. The little guys have it rough, usually showing signs of anxiety, depression and increased body weight within weeks.

The reason for their weight gain can be traced back to an increase in ghrelin, a hunger-causing (orexigenic) hormone produced in the stomach. Once released, ghrelin travels to the brain and binds to its receptors to increase calorie consumption. But not all foods are equal; new research from Carleton University suggests that ghrelin promotes the intake of comfort foods – specifically, carbohydrates- because they decrease the level of circulating stress hormones such as corticosterone.

In the study, researchers first measured the amount of chow that mice ate per day for 21 days. They then chronically stressed out one group of mice by putting a dominant bully into every cage; the two mice were separated by a see-through glass wall to reduce violence. Every day, the mice had 24hr access to a standard, high-carb chow and a 4hr-window to a fattier alternative. Compared to non-stressed controls, the bullied mice drastically increased their total calorie intake, paralleled by an increase in ghrelin levels but surprisingly normal corticosterone levels.

When researchers broke down in the increase in calories by the type of food, they uncovered an unexpected result: stressed-out mice did not eat more fat, but instead opted for more high-carb chow. In fact, this high-carb binge almost entirely accounted for the increase in total calorie consumption.

However, mice chow does contain ~50% of protein and fat. To rule out a preference towards these two macronutrients in combination, researchers repeated the experiment, but with sucrose solution as the alternative to high-carb chow. As before, stressed-out mice increased their intake of chow, but this time, they also doubled their intake of sugar water compared to their unstressed peers. At the same time, their corticosterone levels were normal, suggesting that they were coping fairly well in the face of daily terror.

Why is ghrelin triggering a preference for carbs? The answer might be internal stress management. When researchers feed both bullied and control groups the same standard chow (~50% carbs), effectively restricting access to stress eating, the bullied mice suffered numerous negative health effects. Their ghrelin and corticosterone levels shot through the roof. They had abnormally low blood sugar levels, signalling the onset of metabolic problems. They even showed signs of depression, refusing to swim when dropped into a deep container filled with water.

These data suggest that under stress, ghrelin levels rise and tip food preference towards high-carb rather than high-fat foods. To see if this is indeed the case, researchers turned to a strain of mice genetically engineered to lack ghrelin receptors. Normally, compared to wild-types, these mutants show similar patterns of eating and hormone regulation, although they tend to be slightly smaller. Once stressed, however, they didn’t respond by switching to the high-carb comfort chow, instead increasing their nibbling of fatty foods. Behaviourally, these mice could not cope – in the swimming task, they spent most of their time immobile, succumbing to their fates.

Researchers aren’t yet sure why ghrelin-induced carb – but not fat – intake helps to manage stress. One reason could be bioenergetics: stress alerts the brain that more energy is needed (and soon!) through ghrelin, which in turn increases the preference for glucose – a fast and efficient energy source. Or it could just be a matter of comfort. These mice grew up on standard mice chow, which just happens to be high in carbs. Perhaps, just like you and me, mice simply prefer familiar and comforting foods after a long, stressful day.

Fat cells feel cold?

Not all fat tissues are created equal. There’s the canonical white fat, which we associate with jiggle-ly belly aesthetics, long-term immflamation and Type 2 diabetes. Too much white fat accumulation in the internal organs has even been linked to lower cognitive function in young adults. While these fat cells provide insulation, they’ve always been regarded as inert. That is, they stubbornly hold onto their stored energy, even in chilly environments.

Then there’s brown fat –once thought to only exist in babies- that guards AGAINST obesity and diabetes. If you wipe out brown fatty tissue in animals through genetic deletion, the animals’ weights skyrocket. Brown fat is also more mobile: in response to cold, it releases its stored energy as heat. In other words, you burn off calories.


WAT vs BAT: White adipose tissue (white fat) vs Brown adipose tissue (brown fat). Do we have a winner here? Source:

Sound like a clear-cut good fat/bad fat situation? Think again: new research suggests that “bad” white fatty tissue has a trick up its sleeve. Not only does it respond to cold, it can DIRECTLY sense cold temperature without relying on nerves.

Huh? How can fatty tissues sense temperature?

Let’s backtrack and talk about how brown fat works first. Imagine you’re jumping into the frozen arctic ocean (brrr). The terrible cold almost instantaneously activates sensory nerves in your body. These nerves signal to the temperature control centre – the hypothalamus at the base of the brain – that heat is desperately needed. In response, the hypothalamus releases norepinephrine, the major neurotransmitter in the fight-or-flight sympathetic nervous system. This mobilizes a protein called UCP1 that is present in brown fatty tissue, which triggers it to release its energy stores. Here, activation of the hypothalamus and sympathetic nervous system is absolutely necessary – mice bred without norepinephrine receptors are unable to mount this fat burning response.

Or so it seems. Scientists took these norepinephrine receptor(beta-receptors) lacking mice and exposed them to a chilly 10 Celsius (50 F) for 20hrs. In normal mice, this activated thermogenesis-related genes in two populations of fat: between-shoulder brown fat and subcutaneous (under the skin) fat. Unsurprisingly, in beta-receptor lacking mice, the brown fat response was almost completely obliterated, since they aren’t getting the trigger signal. However, subcutaneous fat more-or-less retained their ability to respond to cold, evidenced by robust thermogenic gene activation. Intriguingly, visceral fat (fat deep in the abdomen surrounding organs) did not respond to cold at all, in both normal and mutant mice. Since one major difference between these two populations of fat is that subcutaneous fat is closer to the surface of the body, scientists wondered if some types of cells in subcutaneous fat can “feel” and respond to cold autonomously, without the need for nerve activation.

So what are these cells? Scientists took lab grown white and brown fat cells and directly cooled them down. For good measure, they also included beige cells – white fat cells that behave somewhat like brown fat – in the study.

Screen Shot 2013-07-04 at 1.16.13 PM

Fig 3a from the paper. It helps to compare white vs beige vs brown. D16, J6 etc are just names of different cell lines.

As seen above, exposure to 31 Celsius (87.8 F) almost tripled the levels of UCP1 mRNA in white (3T3 and J6) and beige cells (D16 and X9), but didn’t change that in brown cells (9EB). Remember in fat-burning canon, UCP1 is the messenger that tells brown fat to start burning off its energy in response to signals from the nervous system. As you can see in the graph below, In white fat cells, the increase of UCP1 is reversible. That is, when heated back up to 37C, expression of UCP1 went back down to baseline. Furthermore, increasing ambient temperature did not induce the same change. This tells us that UCP1 didn’t upregulate due to a “oh my god I’m dying” general stress response, but that its increase is a specific response to decreased temperature.

Screen Shot 2013-07-04 at 1.15.29 PMChronic cooling of white fat cells increased the expression of a whole array of thermogenic genes, hinting that they have acquired increased ability to generate heat. Indeed, lowering ambient temperature significantly increased white fat cell metabolism, as measured by the rate of oxygen consumption.

Since lab grown cells can behave a little wonky at times, scientists also took “primary” cells in fatty tissue obtained from mice and humans and repeated the experiment. As before, both subcutaneous and visceral fat (having a mix of white and brown cells) responded to cold by increasing UCP1; pure brown fat, on the other hand, remained stoic. To confirm that this change is norepinephrine-independent, the scientists also analyzed markers involved in this signalling pathway, and showed that they were not activated.

So what do these results tell us? In all honesty, not that much. It’s really cool that white fat cells can directly sense cold and respond to it – this tells us that unlike popular belief, fatty tissue have a rich and interesting life that exceeds its function of energy storage. But where does UCP1 upregulation lead? It seems like increased UCP1 raises white fat cell metabolism, but does it generate enough heat for it to matter physiologically? Will cold exposure eventually decrease white fatty tissue mass, or will it be gradually repleted in the body? Can fat cells eventually be turned into calorie-burning weight-loss machines?


Polar bear swim, anyone? Anyone? Source:

Maybe their is some truth in promoting cold thermogenesis as a fat-loss measure after all.
Ye L, Wu J, Cohen P, Kazak L, Khandekar MJ, Jedrychowski MP, Zeng X, Gygi SP, & Spiegelman BM (2013). Fat cells directly sense temperature to activate thermogenesis. Proceedings of the National Academy of Sciences of the United States of America PMID: 23818608