Tag Archives: Exercise

Diet, exercise or drugs – how do we cure obesity?

by Simon Cork, Imperial College London, @simon_c_c

October 11th is officially “World Obesity Day”, a day observed internationally to promote practical solutions to end the obesity crisis. The term “obesity crisis” or “obesity epidemic” is often repeated by the media, but how big is the problem? Today, over 1.9 billion adults worldwide are overweight or obese. By 2025, this is projected to increase to 2.7 billion with an estimated annual cost of 1.2 trillion USD. Of particular concern is that 124 million children and adolescents worldwide are overweight or obese. In the UK, this equates to 1 in 10 children and adolescents and is projected to increase to 3.8 million by 2025. We know that obesity significantly raises the risk of developing 11 different types of cancer, stroke, type 2 diabetes, heart disease and non-alcoholic fatty liver disease, but worryingly, we now know that once someone becomes obese, physiological changes to the body’s metabolism make long-term weight loss challenging.

Our understanding of the physiology of food intake and metabolism and the pathophysiology of obesity has grown considerably over the past few decades. Obesity was seen, and often still is seen, as a social problem, rather than a medical issue: a lack of self-control and willpower. We now know that physiological changes occur in how our bodies respond to food intake. For example, hormones which are released from the gut following food intake and signal to the brain via the vagus nerve normally reduce food intake. However, in obesity, the secretion of these hormones is reduced, as is the sensitivity of the vagus nerve. The consequence of this is a reduced sensation of feeling full.

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Imaging of the hypothalamus (a key region for keeping food intake at a balanced level) shows a reduction in activity following food intake in lean men, an effect which was absent in obesity. This effect may relate to a reduction in the body’s responses observed following food intake in obesity, such as balancing blood sugar and signalling that you are full. Furthermore, numerous studies have shown that obese individuals have a reduced availability of dopamine receptors, the structures on cells that respond to the pleasure chemical dopamine, in key brain regions associated with reward. Whether the reduction in dopamine receptor availability is a cause or consequence of obesity remains to be fully explored, but it is likely to be a combination of both of these factors. Individuals with a gene called the Taq1 A1, associated with a decreased availability of dopamine receptors, are more likely to become obese, suggesting that decreased responsiveness to high calorie foods leads to increased consumption in order to achieve the same level of reward. (Interestingly, this same gene is also associated with an increased risk of drug addiction). However, much like drug addiction, hyper-stimulation of the dopamine system (i.e. by consuming large quantities of dopamine-secreting, high calorie foods) can in turn lead to a reduction in dopamine receptor levels, thus creating a situation where more high calorie foods are required to stimulate the same level of reward.

It is therefore clear that obesity is not simply a manifestation of choice, but underpinned by complex changes in physiology which promote a surplus of food consumption, called positive energy balance. From an evolutionary standpoint, this makes sense, as maintaining a positive energy balance in times of abundant food would protect an individual in times of famine. However, evolution has failed to keep up with modern society, where 24-hour access to high calorie foods removes the threat of starvation. The good news is that we know that weight loss as small as 5% can yield significant improvements in health, and can often be managed without significant modification to lifestyle.

 

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Presently, treatment options for obesity are limited. The first line treatment is still diet and exercise; but as the above examples of how our physiology changes show, maintaining long term weight loss through self-control alone is almost always impossible. However, the future does look bright, with new classes of drugs either recently licenced, or in production. Saxenda (a once-daily injectable drug which mimics the gut hormone GLP-1 made by Novo Nordisk) has recently been licenced for weight loss in patients with a BMI greater than 30. However, after 56 weeks treatment, average weight loss was a modest 8kg. Likewise Orlistat (which inhibits absorption of dietary fat, made by Roche) has been on the market for a number of years and shows average weight loss of around 10%. However, it is associated with unpleasant side effects, such as flatulence and oily stools. Presently, bariatric surgery is the only treatment that shows significant, long term weight loss (around 30%, depending on the surgical method used) and is also associated with long-term increases in gut hormone secretion and vagus nerve sensitivity.  Research is currently underway to assess whether the profile of gut hormones observed post-surgery can be mimicked pharmacologically. Studies have shown that administering select gut hormones in combination results in a reduction in body weight and food intake greater than the sum of either hormone when administered in isolation. This observed synergy between gut hormones will undoubtedly form the basis for future pharmacotherapies with improved efficacy, with various combinations currently in both clinical and pre-clinical trials.

For healthcare policy makers, the future obesity landscape does not make for happy reading. A combination of better therapies and improved public health messages are undoubtedly needed to stem the rising tide. However, both policy makers and society as a whole should be mindful that changes in ones physiology mean maintaining long-term weight loss through diet and exercise alone are unlikely to be the whole answer.

Spinning Out of Control? Public Engagement at SPIN Cycle Festival

By Daniel Brayson, @drdanbrayson

SPIN cycling festival, a celebration of all things cycling, took place on the weekend of 12 May 2017 at the Olympia in Kensington, London. Here at The Physiological Society, we thought it would be the perfect opportunity to showcase the wonders of physiology, using funding from The Society’s Public Engagement Grants.

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The premise of our activity was to find some anecdotal dogma, which is prevalent in sports like cycling, and disprove it. Put simply, we went on a myth-busting mission.

A popular assumption among amateur cycling enthusiasts is that it is good to cycle at a high cadence. Discarding the jargon, this essentially means pedalling really fast. Many people think this because successful professional athletes such as Chris Froome, and previously Lance Armstrong, cycled at very high cadences when they were racing in huge competitions such as the Tour de France, the most famous cycling race in the world.

We based our experiment on a paper in one of The Society’s journals, Physiological Reports, from 2015 by Formenti and colleagues titled Pedalling rate is an important determinant of human oxygen uptake during exercise on the cycle ergometer. What the paper essentially showed is that the faster you pedal for a given work rate, the more energy you use.

Bike like the wind

With this in mind, we set out to perform some live experiments on festival-goers. We set up a bike on a smart turbo trainer with a computer that we could use to read measurements. We recruited many willing volunteers over the course of the weekend, fitting them with a device to measure heart rate, and setting them up on the bike.

Using the smart turbo trainer, we set the amount of work that the volunteers would do to 150 watts of power and placed headphones on them. They then sat for 1 minute before beginning to cycle in time with a metronome, or a clicking sound, that was playing through the headphones. We changed the speed of the click at set intervals which meant that the volunteer would change their cadence accordingly. At each cadence, we recorded the heart rate of the volunteer twice, 30 seconds apart.

Pedalling faster, beating faster

We found that as pedalling rate increased, so did heart rate. This can be seen on the left-hand graph below by the line which goes up in diagonal from bottom left to top right. This suggests that faster pedalling did indeed require more energy, even though the power output remained constant.

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Our graph, on the left, comes to a similar conclusion as Formenti and his colleagues on the right. As pedalling rate goes up, so does work rate and energy expenditure. Where Formenti measured oxygen uptake, which requires unwieldy equipment unsuitable for our event, we used heart rate as an easily obtainable proxy measurement, and it agrees nicely with Formenti’s findings.

What does it mean, really?

The real world meaning here is that cycling along the road in lower gears than necessary with high pedalling rate uses more energy than cycling in slightly higher gears but pedalling at a slower rate.

So what’s the deal with Chris Froome?

Chris Froome, and other pro cyclists are not your average human beings from a physiological perspective, so it’s probably a bad idea for us to copy them! The science does show that pedalling quickly at sustained power outputs up to 400 watts, achievable mostly by elite athletes, is far less wasteful. This is because most of the energy gets transferred to the bike in this scenario.

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It was especially dynamic and rewarding to engage with a diverse mix of people and preach the gospel of physiology. I would like to thank all the visitors who staked their reputations by joining our experiment! I would also like to thank The Physiological Society for financial support and especially Anisha Tailor for all of her sage advice. A big thanks to Louis Passfield for his generous support and loan of equipment. Finally, I would especially like to thank all of my wonderful volunteer scientists without whom the whole event would surely have been a disaster Elizabeth Halton, Chris Fullerton, Ozama Ismail, Fulye Argunhan, Elena Wilde, Svetlana Mastitskaya, Xiao Xiao Han, and Nick Beazley-Long.

 

 

Horse or Human: who will win the race?

Place your bets now! Because tomorrow, on 11 June, the 36th annual Horse vs Man Marathon will take place in Llanwrtyd Wells, Wales, where humans will test their mettle against horses on 22 miles of mountainous terrain. Who will win this year?

On flat terrain, it would be a no-brainer: horses clearly have a significant advantage over humans. With their lean and muscular physique, thoroughbreds can reach speeds of up to 55 mph, while the world’s fastest human, Usain Bolt, lags behind with a top speed of only 27 mph. So how do horses reach such impressive speeds? We can find some clues by studying their anatomy and physiology.

The first proper studies began over 200 years ago, after the death of a particularly special racehorse, Eclipse, who was never beaten throughout his racing career from 1769 to 1770. His extraordinary success prompted the founding of the Royal Veterinary College in 1791 and ever since then, veterinary scientists have been making great strides in finding out what it is that allows horses to run so fast. It turns out that several factors play a role, including a big heart and the ability to increase heart rate to a remarkable degree:

 

Horses’ ability to increase the amount of blood pumped by the heart around the body to the muscles makes all the difference in a race, and that is helped by the spleen, which contains a store of oxygen-carrying red blood cells that are released into the bloodstream during exercise. They have other tricks up their sleeve too:  compared to humans, they have a far greater tolerance of increased body temperature and blood acidity, both of which go up fast during intense exercise.

We can find other clues to horses’ speed in their long and light-weight legs, which have very springy tendons that save energy needed to move quickly. So where does the muscular power come from?  The leg muscles aren’t in the lower legs as humans’ are, but tucked up close to the body, connected to the lower legs by very long tendons, which also generate  ‘springiness’. As with all four-legged animals, the muscles in the back, neck and abdomen also contribute to the ability to gallop. The quickest racehorses have lots of fast twitch fibres in these muscles, helping them to generate more energy for movement via both aerobic and anaerobic respiration.

Also unlike humans, the stride in galloping directly controls the timing of breathing: the huge weight of the hindgut acts like a piston on the lungs at the front, sucking in the maximum amount of air possible and then expelling it rapidly, as the torso moves with each step. This neat trick means that horses can move large volumes of air in and out of the lungs very quickly, helping to maintain their performance for longer.

And, of course, no racehorse is complete without its rider – who also plays a key role in the horse’s performance. Have you ever wondered why jockeys ride crouching over the horse, rather than sitting upright? Well, this is known as the ‘monkey crouch’ and was invented by Americans in the 1890s in order to improve horse speeds. This position separates the stride of the horse from the rider i.e. as the horse moves forward, the rider moves back, and vice versa. In this way, the rider takes up some of the effort required to move forward, enabling the horse to save some much needed energy for the race.

But what about humans? How can we possibly measure up to all this? By levelling the playing field, to something less level – which is exactly what the Horse vs Man Marathon has done, by holding the race on mountainous terrain. This gives humans a fighting chance – so while it’s true that horses have dominated the Marathon so far, there have been two occasions when a human has won the race. How come?  On rough hilly ground, the horses’ ability to reach and maintain their peak speed is severely reduced. Humans are much lighter, so the changes in direction needed on rough ground take less energy than for the much larger horses.

If we look at the cases where humans have won the race, one factor immediately jumps out, and that is: hot weather. It’s not immediately clear why that favours humans. Our ability to sweat, which cools us down in hot weather, is shared with horses. But, being smaller, we have relatively more skin to sweat from than do horses, and that may be a greater benefit than horses’ greater tolerance of high body temperature. And humans can take on extra fluid during the race, replacing that lost in sweat, without having to stop – something their equine competitors can’t do.

So, who will win tomorrow? The weather forecast predicts maximum temperatures of 19°C, so the human participants will have to draw on all of their abilities, to be in with a chance of winning.

Who will you place your bet on?

 

Researcher in the Spotlight February 2016

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Dr Michael J. Joyner, M.D. is interested in how humans respond to various forms of physical and mental stress during activities such as exercise, hypoxia, standing up and blood loss. Dr Joyner will give a plenary lecture at our BBEP meeting, 6-8 March 2016 in Nottingham, UK on ‘Physiological limits to exercise performance: Influence of gender’. You can watch the live steam here.

 

What is your research about? 

I do integrative physiology studies in humans. My main interests are exercise physiology, blood pressure regulation, and regulation of metabolism. I am also interested in what world records in sport can tell us about physiology and also how the interplay between reductionism and holism in research informs science policy. 

How did you come to be working in this field and was this something you always wanted to do?

I started in the late 1970s as a human subject in a study on the lactate threshold and distance running performance, and was hooked from day 1. A career focused on physiology research hit me like a thunderbolt at age 19. Until then I had been an indifferent student. The investigators in that original study were extremely encouraging and set the stage for what has followed.

Why is your work important? 

The work on exercise largely focuses on the regulation of skeletal muscle blood flow. The mechanisms that evoke the massive vasodilation during exercise are only now beginning to be understood and this has been one of the great intellectual puzzles in biology over the last 150 or so years. The work on blood pressure has shown that women and men regulate blood pressure very differently and that especially for women things change dramatically with age. This work has relevance for the understanding, prevention and treatment of hypertension. My interest in blood pressure also extends to clinical monitoring (I am an anaesthesiologist) and how it can be refined to improve patient care. The studies on metabolic regulation focus on the non-oxygen sensing role of the carotid bodies and how they might contribute to things like the diabetes frequently seen in patients with sleep apnoea. The world record stuff is just plain fun and my interest in science policy is about trying to move the scientific and medical communities away from their current DNA centric world view.

Do you think your work can make a difference?  

Yes, there is a translational element of almost everything my lab does and I like to think we can help link basic science observations to the whole human. By understanding physiological regulation in humans, we can then see how it goes off the rails in disease states and think about how to intervene to essentially restore homeostasis.

What does a typical day involve? 

I get up early around 5AM and answer my e-mail and read the New York Times, at about 6 I exercise for 30-60 minutes and then head to St Marys Hospital which is part of the Mayo Clinic. My house is only about 2km from the hospital and usually I ride my bike. Four days per week, I am in the lab working with my staff and fellows. I am lucky to still participate in the data collection in our invasive studies but beyond that it is a lot of editing, discussing ideas, generating proposals etc. Over the years, the Fellows in the lab have been superb and almost all now run independent programs at “Research” Universities. My technical staff and research nurses have all been with me for years and the team is very strong.

What do you enjoy most in your job? 

Almost everything! The interactions and chance really to learn from the students and fellows is the gift that keeps giving.

What do enjoy the least?

The compliance bureaucracy can get a little convoluted and frustrating at times. 

Tell us something about you that might surprise us…

In high school I was an all-state French Horn player.

What advice would you give to students/early career researchers? 

Do what you are interested in and don’t buy into the idea that a fulfilling life is a linear engineering exercise. It is nine-ring circus.

 

 

Researcher in the Spotlight May 2015

Professor Mike Tipton is Director of Research for the Department of Sport & Exercise Science at the University of Portsmouth.

What is your research about?

It is about the physiological and pathophysiological responses to extreme environments and the selection, preparation and protection of those who enter such environments accidentally or for work or play. We try to give advice based directly on our applied work, or on the practical application of the findings from our basic research.

How did you come to be working in this field and was this something you always wanted to do?

From an early age, I, like many people, had an interest in how the body works. As a young person I was a swimmer, during my MSc at King’s College, London in 1982 I developed an interest in temperature regulation. As part of the course we visited the Institute of Naval Medicine where Surgeon Commander Frank Golden (Later Surgeon Rear Admiral Golden) was running an experiment on swim failure in cold water. It was the perfect experiment for me; a combination of temperature regulation and swimming – I was hooked. Frank and I then worked together for 32 years until his death last year.

Why is your work important?

I think it is important for different reasons. At one level, we advise industries, the military, elite sportspeople and explorers on how to prepare for extreme environments, protect against these environments and maintain performance in them. As an example, our work identified the need for, and developed the first UK helicopter passenger emergency underwater escape emergency breathing aid (“Air Pocket”) for use by those travelling offshore in the oil industry. At another level, I have spent my entire career trying to reduce the global burden of drowning through research that focuses on the physiological responses to immersion, especially in cold water. The numbers are imprecise, but around 3,000 people “drown” each day around the world. In the UK, although the number is thankfully falling, we still lose about one adult a day and one child a week due to drowning – drowning is the second most common cause of accidental death in most countries of the world but in comparison with other epidemics it is largely unrecognised. A large part of our work has examined the physiological and pathophysiological responses to immersion and the rescue, resuscitation and treatment of immersion casualties. It ranges from the cause of sudden death on immersion to prolonged survival underwater.

Do you think your work can make a difference?

I hope so. I know that many search and rescue (SAR) organisations and training establishments in the UK and abroad use our work in the training of their personnel and in their search and rescue policies and medical protocols. Our work is also used by leading industries, for example in the energy sector, to determine their policies for sending workers into different environments and determining the selection and protection of their work force. I am pretty confident that we have “impact”.

Therapeutic hypothermia has been shown to prevent brain damage. Can you tell us a bit more about it?

Hypothermia is something of a “twin edged sword”. On the one side hypothermia, on average, causes cardiac arrest at a deep body temperature of about 25 °C, although the range on this figure is very large with the lowest deep body temperature recorded with complete recovery being below 14°C. On the other side we have proposed as long ago as 1997 that selective brain cooling during submersion is the reason why some people, particularly children have survived up to 66 minutes of submersion in very cold water with full recovery. The hypoxic survival time of the brain is extended by hypothermia; with cerebral activity and therefore oxygen demand falling close to minimal levels at a brain temperature of 22°C. We think that in the right circumstances the initial cold shock response to immersion in cold water and the process of drowning, both of which are normally extremely hazardous, can result in a “drowned” individual with a brain protected from hypoxia by hypothermia. The same mechanism underpins some of the benefits of therapeutic hypothermia.

Prolonged survival underwater is a very rare occurrence, but when it happens, the individual is retrievable. From the applied perspective, this is important knowledge for the SAR community and we have produced a decision making guide for this group  that, for example, forms part of the Fire & Rescue Service National Operational Guidance Programme for in-water rescue.

You are currently “touring” your GL Brown Prize lecture around the UK and Ireland. In your presentation you’re talking about “life at the extremes” and our limits of physiological adaptations to environmental extremes. Would you say our body is more heat tolerant, due to our “equatorial ancestry”, or are both hot and cold environments presenting an equal challenge?

We are certainly a tropical animal; we are designed to live naked in an air temperature of 28 °C with a mean skin temperature of 33°C and deep body temperature controlled between 36.5 °C and 39 °C depending on what we are doing. The thing that makes us different is our intellect. If we were to rely on just our thermoregulatory system, we would be confined to our equatorial origins. Our intellect has allowed us to inhabit the rest of the planet via the use of clothing, building and heating. In so doing we have recreated our thermal tropical origins in the microclimate next to our skin, but in so doing we have reduced the stimuli to adapt in the ways other animals demonstrate.

Under normal, resting circumstances we have a deep body temperature (37 °C) that is about 7 °C below the upper lethal limit (hyperthermic death) and 12 °C  above the lower lethal limit (hypothermia death). Despite the bigger margin to death from hypothermia, we are better suited to lose heat than gain it: for each litre of blood at 37 °C that flows through the skin and returns to the deeper tissues at 36°C the body loses roughly 4.2 kJ of heat. As the maximum skin blood flow can be as much as 3-4 L.min-1, the same 1°C fall in the temperature of the blood off-loads up to 280W. In contrast to most other mammals that have none, humans have about 2.5 million sweat glands distributed over most of the body surface in densities ranging from 100 to 600 per square centimetre. If we evaporate all the sweat we can produce per hour (about 2L.hr-1) we can lose about 1200 W of heat. In contrast, in the cold piloerection (raising the hairs on our skin) traps little air because of our hairless state, maximum shivering only produces about 600W of heat. Finally, although body fat has similar thermal characteristics to cork, when maximally vasoconstricted we do not have much subcutaneous body insulation to counter cooling (although the trend seems to be for humans to have more insulation)!

What does a typical day involve?

Start work at home about 5am, usually reading, writing and emailing. Motorbike to work about 08:45, get in at 09:15. Meet colleagues and students to discuss some of the 20-30 projects (from experiments to writing projects) we have running at any given time. Maybe a meeting (see below), working lunch at the Café Parisien 150m from my office. Visit lab, discuss experiments, chat to PhD students, work on publications, administration (see below). Go to gym or do some exercise. Eat dinner, work until 21:00 then fall asleep in front of a film (my family evaluate films by how long it takes me to fall asleep watching them). Bed at 23:30.

Actually I do not have many “typical” days – I travel a lot giving talks, working with end-users of our work and doing field experiments and therefore spend quite a lot of time in hotels and away from the office.

What do you enjoy most in your job?

Discussing protocols and new data with students and colleagues. Meeting, talking with and helping those in the rescue services – great people.

What do you enjoy the least?

Administration and unnecessary, over-bearing and inhibiting bureaucracy. Meetings that go on for longer than a rugby match. The false distinction between “pure” and “applied” research; I agree with Sir Peter Medawar:  “the distinction between pure and applied science is false. There are only two types of science, good and bad”.

Tell us something about you that might surprise us…

I do the Nice Ironman every 5 years – it is cheaper than private health care. The next one is scheduled for 2019.

What advice would you give to students/early career researchers?

Be inquisitive and develop as wide a knowledge and interest base as you can. As we specialise and learn more and more about less and less, the person who can look across several areas with knowledge and understanding becomes a precious commodity. Be confident in your own abilities, including the ability to have good ideas. Be collegiate: talk and network to as many people as you can. If you haven’t already, learn to listen. Try not to prioritise “timeliness” over “quality”. Check out: https://www.linkedin.com/pulse/career-advice-i-wish-had-25-shane-rodgers.