Tag Archives: physiology

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.

Watchers on the wall: Microglia and Alzheimer’s Disease

By Laura Thei, University of Reading, UK

The watch, worn by years of use, sits ticking on our table for the first time in two years. It has a simple ivory face and is the last memorabilia my partner has from Grandad Percy. Percy passed from us after a long personal battle with dementia, specifically Alzheimer’s disease. It is in his name that my partner and I will take to the beautiful winding pathways beside the Thames, to raise money for the Alzheimer’s Society.

We will be taking part in a 7 km Memory Walk, with thousands of others, some my colleagues from the University, each sponsored generously by friends and families, each who has had their life touched by this disease in some way. Last year nearly 80,000 people took part in 31 walks, raising a record £6.6 million. As a researcher in Alzheimer’s disease, I am acutely aware of every penny’s impact in helping to solve the riddle of dementia.

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Alzheimer’s Society Memory Walk

Alzheimer’s disease is ridiculously complicated. Oh, the premise is simple enough: two proteins, amyloid beta and phosphorylated tau, become overproduced in the brain and start to clog up the cells like hair down a plug. This causes these cells to be deprived of nutrients, oxygen and other vital factors that keep them alive. This eventually causes regional loss in areas specific to memory and personality. It’s simple in theory, but the reality is that we still have much to learn.

Current, extensive research is starting to answer these questions and whilst there is a growing list of risk factors – genetic (APOE4, clusterin, presenilin 1 and 2) and environmental (age, exercise, blood pressure) – confirmation only occurs when a brain scan shows the loss of brain region volume in addition to the presence of amyloid beta and tau. This means that by the time someone knows they have the disease, it’s possible that it’s already been chugging away at their brains for some time.

So we need to push diagnoses earlier. To do that we need to look at the very early stages of the disease, down to a cellular level, to find out how we can prevent the build-up of amyloid and tau in the first place. This is what I, the group I’m in, and many other researchers nationally and globally are striving to do.

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In a non-active state, microglia lie quietly surveying their local area of the brain. ©HBO

I am specifically focusing on the immune cells of the brain, microglia, and their contribution. Microglia are the most numerous cells in the brain. They act as the first line of defence, so their involvement and activation is often seen as an early sign of disease progression. Like all good defences, they tend to be alerted to damage before it becomes deadly. But, like the neurons (the basic building blocks of the brain), microglia are also susceptible to the disease. If they die, does that leave the brain more vulnerable to further insult? That is what I would like to know too!

In a non-active state, microglia lie quietly surveying their local area of the brain. When activated by a threat to the brain, they cluster around the targeted area, changing shape in the process. They then enter one of two states. The pro-inflammatory state releases molecules that attack the harmful pathogens directly, and the anti-inflammatory state releases ones that promote healing and protection of the area.

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Microglia can change shape to either attack pathogens or protect the area. ©Nickelodeon

With Alzheimer’s, microglia are activated by the accumulation of amyloid, not damage. They absorb the amyloid beta, and in the process, trigger the pro-inflammatory response. This then increases the permeability of the brain’s blood supply, allowing immune cells into the brain to assist removal of the excess protein. However, in the brain of Alzheimer’s patients, the amyloid beta production outdoes the microglia’s ability to remove it. This creates a perpetual cycle of pro-inflammatory response, releasing molecules that can kill cells in the brain. It is unclear whether there is a threshold between beneficial or detrimental in the microglial response.

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Microglial response to fight Alzheimer’s Disease can become detrimental. ©2011 Scott Maynard

Given the importance of microglia in neurodegenerative diseases, a new field of microglial therapeutics has recently emerged, ranging from pharmacologically manipulating existing microglia by switching their response status, to inhibiting microglial activation altogether. Continued research and clinical efforts in the future will help us to improve our understanding of microglial physiology and their roles in neurological diseases.

We’re making progress, but there’s still a long way to go, which is why every penny counts!

10 Epic Physiology Cakes

It’s that time of year again! Great British Bake-Off time Bio-Bodies Bake-Off time! To celebrate the return of the baking season, staff at The Physiological Society have been reminiscing about past entries to our annual hunger-inducing competition. From muscle to kidneys, representing health or disease, grossly graphic or detailed to the molecular level, check out our 10 favourites, in no particular order. If you haven’t quite decided what area of physiology you would like to cover in this year’s competition, these delicious treats might give you some inspiration!

  1. Operation Indigestion: Stomacake, by Anousha Chandran, Kujani Wanniarachchi, Susannah Watson and Anna Higgins

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Rosie Waterton, our Governance Manager, admits to having limited physiology knowledge, but confesses to a somewhat higher than average level of cake eating experience. “This cake is probably my favourite,” she explains. “There is something darkly ironic about demonstrating indigestion through something so delicious and tempting! I also just love a good pun.”

  1. Anatomy of the Face, by Sophia Rothewell

Rosie couldn’t help picking a second choice when she saw Anatomy of the Face. She was struck by its uncanny resemblance to a Game of Thrones white walker…. only colourful.

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  1. Not Kidneying Around, by Carlotta Meyer

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Jen Brammer, our Membership Engagement Manager, another pun fan, loved this delicious masterpiece, Not Kidneying Around. Whilst unsure about the anatomical accuracy, she did enjoy debating whether the appendages were pickled onions or grapes!

  1. Upper Leg, by Jack Croft

Bobby Harrop, our summer intern and a keen cyclist, was immediately struck when seeing the cake titled Upper Leg.

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He commented: “when cycling, I rely heavily on the input of my upper legs and I was fascinated to see this submission highlighting the complexity of the Rectus Femoris and Vastus muscle group whilst including real detail in the muscular tone. Plus in terms of parts of the body to eat, muscle is probably the most appetising as it is mostly protein!”

  1. The Effects of Drug Abuse on the Human Body, by Amy Yang

Anisha Tailor, our Outreach Officer, has probably spent the most time browsing through the #Biobakes entries. Each year, she develops a minor obsession with the hashtag and eagerly awaits the first entry!

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“I think my favourite cake of all time has to be the one titled The Effects of Drug Abuse on the Human Body. It was a bit of a shock to find it in my inbox at first, but it became one of my firm favourites of 2016: it’s visceral, yet educational, although perhaps not very appetising”.

  1. Guts, by the students from Tiverton High School

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Hannah Woolley, Editorial Assistant, spent far too long deciding which one was her favourite. She finally decided she liked this one the most because it looked gross.  “It’s a compliment! I particularly liked the attention to detail that went into the blood splatter.”

  1. A Tasty Great Cake, by Katie Pennington

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Daïmona Kounde, our Communications Officer, loves picking yummy cake photos for our social media. “I have a soft spot for the DNA-themed cakes,” she says. “My favourite, A Tasty Great Cake, is not just beautiful and colourful, but it also has the A, T, C and G bases paired correctly, with a colour key to boot. The ‘base necessities’ pun in the cake description was just… icing on the cake (sorry)!”

  1. Synapse, by Nicola Armstrong

Angela Breslin, our Education Manager, has been following the BioBakes competition ever since it started, and continues to be amazed by the high standard of entries each year.

“It’s a difficult choice but if I had to choose just one, it would be the cake titled simply Synapse, for the sheer amount of detail and the elegant way in which it shows how an action potential travels between nerves – somehow managing to show physiology in a single snapshot. It’s also a beautiful bake!”

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  1. Louis’s Lungs, by Louis Christofi

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Samantha Chan, Events & Marketing Officer, has tried baking different cakes and biscuits in the past, but has never attempted a BioBakes cake. Sadly, staff aren’t allowed to enter, so she will just have to make do with all your entries – or make some cakes for the office! Her favourite was Louis’s Lungs, which shows the structure of the lungs.

  1. Your baking masterpiece!

We can’t wait to be amazed by this year’s entries. Maybe yours will make it to our next round of favourites! If you’re still a bit stuck for ideas for BioBakes 2017, browse our Twitter hashtag #Biobakes, read about one of our previous winners, or take a look at our 2014, 2015 and 2016 Facebook albums!

All you’ve got left to do is bake! For full terms and conditions visit our competition page. Entries are due in by 5pm, Friday 6 October, and photos must include the #Biobakes photo entry form to be considered.

Making sense of stress in the wild

By Kimberley Bennett, Abertay University

Imagine leaning forward over the edge of a precipice. Lurching back to safety, you picture the forest hundreds of metres below. Is your heart racing? Are your palms sweating? Our body’s stress response to an ever-changing environment enables us to survive and flourish.

Physiologists play a crucial role in developing our understanding of the mechanisms involved. To highlight the exciting work that they do, our 2017 theme is ‘Making Sense of Stress’. Follow the conversation on Twitter using #YearOfStress.

Launching the theme will be Dr Kimberley Bennett’s talk, ‘Making sense of stress in the wild’, at the Association for Science Education’s (ASE’s) Annual Conference on 6 January 2017. Read a teaser to her talk below!

Coping with stress is a major issue in modern society, but it’s easy to forget that wildlife experiences stress too. Without enough water, plants wilt and die and whole crops fail; without the right habitat, a small population of rare animals dwindles and dies out, causing extinction of the species; a whole coral reef bleaches when the water temperature gets too high, causing catastrophe for the ecosystem, and massively increasing flooding risk for people living by the coast. We really need to pay attention to stress in the wild because the consequences can herald disaster.

Stress is the biological response to a major challenge, whether it’s at the whole organism or cell level. A gazelle in the Serengeti chased by a lion experiences the same stress responses that we do – a surge of adrenaline and cortisol that cause increased heart rate and blood pressure and a release of glucose. These changes make sure there is enough fuel and oxygen to cope with increased demand at the tissue and cell levels. Sudden change or mismatch in the supply of oxygen and fuel leads to increased production of reactive molecules called ‘free radicals’ that can damage cells. If the temperature gets too hot too fast or if the acidity of the cell changes too much, proteins (the molecules that catalyse reactions, transport substances and provide structure) can fall apart or unravel. So cells have to increase their defence mechanisms too. Cellular defences include antioxidants that mop up the free radicals, and heat shock proteins, which refold damaged proteins and stop them forming a sticky mess inside the cell.

The old adage that what doesn’t kill you makes you stronger is often true: short term ‘good stress’ builds up these defences and makes organisms better able to deal with stress later on. However, sometimes defences can be overwhelmed or can’t be maintained for long periods. The organism then experiences the same sorts of problems as people under chronic stress: lower immunity, altered metabolism, anxiety and tissue damage (like ulcers). In wildlife, this can have major consequences for breeding success or even survival. By affecting whether organisms survive and thrive, stress dictates which individuals contribute to the next generation. Stress shapes population dynamics, lifestyle and adaptations, and is therefore a powerful agent of natural selection.

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I work on seals, top marine predators that are used to stress as a normal part of their existence. Their individual and population level health is an indicator of ecosystem health. Seals are air breathing mammals that feed underwater, but need to come to the surface to breathe, and to come ashore to rest, breed and moult. Diving on a single breath hold means they need to conserve oxygen; to do this, blood flow is restricted mostly to the heart and brain, so that other tissues may experience free radical production while oxygen levels are low. On land, seals need to fast, often while they are doing energy-demanding activities i.e. shedding and replacing hair, producing milk, defending pups or territory, or undergoing rapid development. Injury and infection can occur from skirmishes or trampling. Seals may have to reduce their defences to deal with all these demands on their energy when food is not available. In addition to their ‘lifestyle stressors’, seals face stress from competition for access to fish, disturbance on haul out or displacement from foraging grounds as a result of human activity, and the accumulation of contaminants in their blubber.

We need to understand natural and man-made causes of stress in wild populations, distinguish good stress from bad stress, and understand how multiple stressors at the same time can create problems. That means we have to have effective tools to measure stress and its consequences in organisms that can’t tell us how they feel. But can we measure stress responses in wildlife? What do they mean in context? And can they help in managing stress in the wild?

I will address all these questions and more at the ASE’s Annual Conference on Friday 6 January 2017, as part of the annual Biology in the Real World (#BitRW) lecture series. Please drop by the Knight Building, LT 135, at the University of Reading, at 1.30pm to find out more!

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