Tag Archives: obesity

Obesity: hamsters may hold the clue to beating it

Apply by 28 February for our Research Grants of up to £10,000 (over a 12 to 18-month period). This scheme supports physiologists in their first permanent academic position or returning to a permanent position after a career break, to provide support for their research or to provide seed-funding to start a new project. Gisela Helfer was a 2017 awardee of this grant, and you can read about her research below:

The global obesity crisis shows no signs of abating, and we urgently need new ways to tackle it. Consuming fewer calories and burning more energy through physical activity is a proven way to lose weight, but it’s clearly easier said than done. The problem with eating less and moving more is that people feel hungry after exercise and they have to fight the biologically programmed urge to eat. To develop effective ways to lose weight, we need a better understanding of how these biological urges work. We believe hamsters hold some clues.

Hamsters and other seasonal animals change their body and behaviour according to the time of year, such as growing a thick coat in winter or only giving birth in spring. Some seasonal animals can also adjust their appetite so that they aren’t hungry when less food is available. For example, the Siberian hamster loses almost half its body weight in time for winter, so they don’t need to eat as much to survive the winter months. Understanding the underlying physiological processes that drive this change may help us to understand our own physiology and may help us develop new treatments.

How hungry we feel is controlled by a part of the brain called the hypothalamus. The hypothalamus helps to regulate appetite and body weight, not only in seasonal animals but also in humans.

Tanycytes (meaning “long cells”) are the key cells in the hypothalamus and, amazingly, they can change size and shape depending on the season. In summer, when there is a lot of daylight and animals eat more, tanycytes are long and they reach into areas of the brain that control appetite. In winter, when days are shorter, the cells are very short and few.

These cells are important because they regulate hormones in the brain that change the seasonal physiology of animals, such as hamsters and seasonal rats.

Growth signals

We don’t fully understand how all these hormones in the hypothalamus interact to change appetite and weight loss, but our recent research has shown that growth signals could be important.

One way that growth signals are increased in the brain is through exercise. Siberian hamsters don’t hibernate; they stay active during the winter months. If hamsters have access to a running wheel, they will exercise more than usual. When they are exercising on their wheel, they gain weight and eat more. This is true especially during a time when they would normally be small and adapted for winter. Importantly, the increased body weight in exercising hamsters is not just made up of increased muscle, but also increased fat.

We know that the hamsters interpret the length of day properly in winter, or, at least, in a simulated winter day (the lights being on for a shorter duration), because they still have a white winter coat despite being overweight. We now understand that in hamsters the exercise-stimulated weight gain has to do with hormones that usually regulate growth, because when we block these hormones the weight gain can be reversed.

When people take up exercise, they sometimes gain weight, and this may be similar to what happens in hamsters when appetite is increased to make up for the increased energy being burned during exercise. This doesn’t mean that people shouldn’t exercise during the winter, because we don’t naturally lose weight like Siberian hamsters, but it does explain why, for some people, taking up exercise might make them feel hungrier and so they might need extra help to lose weight.


We need to find ways to overcome appetite. Lucky Business/Shutterstock.com

What we have learned from studying hamsters so far has already given us plenty of ideas about which cells and systems we need to look at in humans to understand how weight regulation works. This will create new opportunities to identify possible targets for anti-obesity drugs and maybe even tell us how to avoid obesity in the first place.

By Gisela Helfer@gi_helfer and Rebecca Dumbell

(This blog was originally published on The Conversation.)

Why dieting is bad for you

By Simon Cork, Neurophysiologist, Imperial College London, @SimonCorkPhD

According to a 2016 survey of 2000 people in the UK, almost two thirds of us are on a diet at any one time. For most people, the typical diet consists of eating a salad for lunch, and cutting out desserts and snacks. NHS guidelines for weight loss recommend reducing calorie intake by around 600 calories each day. But is this advice right?

There is a theory among many scientists in the obesity field that body weight is fixed around a “set point”. That means that for the majority of people, body weight is typically static (unless drastic changes are made to exercise or diet). Any fluctuations in our body weight are compensated for by either increasing or decreasing energy input or output. You might feel this if you’re on a low calorie diet by feeling constantly tired and feeling like you just want to sit down. That’s your body’s way of trying to conserve energy.

One method our body uses to keep its weight constant is a hormone called leptin, released by fat cells into our bloodstream. The more fat we have, the more leptin we have flowing through our blood. Normally, leptin acts in the brain to restrict appetite, effectively acting as the brake to restrict major changes in body weight. Minor increases in fat lead to increases in leptin, which reduces appetite. Loss of body fat causes decreases in leptin and thus increases in appetite to compensate. Leptin is therefore the body’s messenger to the brain, informing it of our weight.

The problem occurs when we override the effects of leptin, typically with respect to its appetite-restricting effects. More fat means more leptin, which should reduce our appetite, and thus reduce our body weight back to what our brains perceive as “normal”. However, if we override these effects (e.g. by ordering dessert after starters and a main, or eating large portions, thus eating past the point of feeling full), our brains eventually become resistant to leptin.

simon cork dieting

Leptin levels are directly correlated with body weight. Bronsky et al, 2007.

This leptin resistance effectively means that our brains are tricked into underestimating what our body weight truly is. Although a 150 kg person has more circulating leptin than a 70 kg person, the extra leptin doesn’t decrease appetite as it should because the brain has become resistant to leptin: it needs more leptin to have the same effect. The brain is therefore “tricked” into thinking the body has less fat than it really does.

This has significant consequences when people who want to lose weight go on low calorie diets. As we restrict food intake, we lose body fat. For reasons not fully understood, the levels of leptin fall at a greater rate than body fat. Our brains react by activating mechanisms to restrict any further loss of body fat and promote energy storage. One such reaction is lowering the resting metabolic rate – effectively the minimum amount of energy required to keep us alive.

You may remember a US TV series called “The Biggest Loser”. This show took overweight or obese people and subjected them to a gruelling exercise and diet regime. The contestant who lost the most weight by the end of the show won a significant cash prize. In 2016, the results of a study were released which followed the contestants after they finished the show. They found that almost all contestants regained their weight and found that some regained more weight than before they started.

And this is the crux of the matter. It has been found that people who go on crash diets significantly reduce their resting metabolic rate – effectively, they are using less energy just by being alive than before the diet. And this metabolic rate may never recover – even after stopping the diet.

This may explain why a number of contestants regained more weight after the show than they started with. Their bodies are constantly fighting against a famine. It may also be why most people who go on a diet fail to maintain their low body weight long term. This is the key issue that many people developing weight loss therapeutics are facing.

simon cork dieting 2

Calorie restriction (CR – blue line) results in significant decreases in resting metabolic rate (RMR) Davoodi et al, 2014

For many people, losing weight is relatively easy. Simply restricting calories and/or increasing the amount of energy we use, usually by exercising, will result in weight loss. Maintaining that weight loss is the key issue. Exercise is often the key to maintaining weight loss, but is difficult to maintain the necessary levels of exercise required to compensate for the decreases in energy use that occurs following dieting.

Scientists are currently investigating how to manipulate the body weight set point, by both re-sensitising the body to leptin (i.e. countering the leptin resistance), and/or by increasing the levels of naturally occurring hunger-suppressing hormones that our bodies release after eating.

If decades of dieting advice has told us anything, it’s that dieting doesn’t work to bring about long-term weight loss. But importantly, by permanently reducing the resting metabolic rate, dieting may actually be preventing our bodies ability to lose weight in the future.

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.


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.



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.