More people are overweight or obese than ever before, prompting the World Health Organization to acknowledge this as a ‘Globesity’ epidemic. The number of people worldwide who are overweight (BMI higher than 25) or obese (BMI higher than 30) has skyrocketed in recent years, from an estimated 200 million adults in 1995 to over 300 million as of 2000 (WHO press release, 2003). Data from a recent analysis of 188 countries suggests that the number has risen even further in the last decade, with more than a third of adults qualifying as overweight (Ng et al., 2014). In some countries more than half of all men and women are obese. As adults over the age of 15 account for around 75% of the world’s population, this suggests that there are now an astonishing 2.12 billion adults worldwide who are overweight.
Even more worrying is the fact that the prevalence of overweight and obesity increased by nearly 50% in children and adolescents between 1980 and 2013. As of 2013, more than one in five girls and nearly one in four boys living in developed countries were overweight, as were more than one in eight children in developing countries (Ng et al., 2014). Children who are overweight have reduced lifespan, and are at a high risk of spending their lives living with disability.
In 2010, an estimated three to four million deaths were attributed to being overweight or obese, with people losing 3-9% of their projected lifespan to these conditions (Ng et al., 2014). Being overweight significantly increases a person’s risk of cardiovascular disease, diabetes, joint issues, back pain, cancer, hypertension and premature death. Beyond the physical implications, weight can also have a major effect on a person’s sense of wellbeing and happiness, with several studies showing higher levels of depression in those who are obese, including one recent analysis of data from over 9,000 adults in the U.S. (Simon et al., 2006).
HOW SITTING MANIPULATES HORMONES AND AFFECTS APPETITE
Metabolic hormones, such as leptin and insulin play a key role in regulating energy metabolism, in part by acting on the central nervous system, specifically the hypothalamus in the brain. The hypothalamus controls a significant portion of the body's hormonal (endocrine) system through the pituitary gland. In addition to helping regulate energy expenditure and storage, the hypothalamus also plays a role in controlling body temperature, appetite and digestion, and even our circadian rhythms.
The hypothalamus gathers information about short-term energy supply, satiety, and hunger via the vagus nerve that connects the brain to the gut. It also gathers information about long-term energy storage and helps us to recognise when we need to consume more calories for future exertion and longer term survival. Incredibly, just two hormones, leptin and insulin, provide this key information to the hypothalamus to help maintain energy homeostasis. We’ve already mentioned insulin and its effects on metabolism, so let’s turn our attention to the second hormone, leptin.
Leptin (from the Greek, leptos, meaning thin) was first discovered in 1994 in obese mice. It is a small protein that is created in fat cells (adipocytes); the more body fat a person has, the higher their blood leptin levels. If ghrelin is the ‘hunger hormone,’ leptin is the opposite, telling the brain – specifically the hypothalamus – when we have stored enough energy and no longer need to consume calories. In a healthy system, gastric distension (stretching of the stomach) after a meal results in a signal being sent via the vagus nerve (the gut-brain axis) prompting the release of leptin from fat stores. When leptin crosses the blood-brain barrier and reaches the hypothalamus, it triggers the brain to suppress appetite and increase physical activity.
After it was discovered, leptin attracted the attention of many pharmaceutical companies who considered it the holy grail for weight management. These companies poured huge amounts of money into research and manufacturing leptin-based supplements, but the hormone would never achieve the anticipated success, leaving researchers scratching their heads. What went wrong? Why didn’t leptin live up to its early promise as a weight management tool?
The short answer is that the problem isn’t leptin deficiency, but rather leptin resistance, i.e. it’s not the amount of leptin in the blood that matters, but how well the brain responds to it.
Leptin deficiency is actually very rare and results from either a genetic mutation, brain trauma, or brain surgery. Without proper treatment, people with leptin deficiencies typically become obese and experience other significant and related health issues. The administration of leptin in leptin deficient people serves to normalise their appetite and energy homeostasis, helping them achieve healthier body weights. Leptin resistant individuals, however, do not respond to the administration of supplemental leptin, hence the frustration of those pharmaceutical giants.
EXPERIENCING FALSE HUNGER
There’s been plenty of discussion surrounding insulin resistance in recent years, but very little when it comes to leptin resistance. This phenomenon is becoming increasingly common and is most often seen in people who are obese and/or sedentary. In a state of leptin resistance, an individual has high blood levels of leptin (corresponding to a high degree of body fat), but the brain fails to respond to the hormone. This prompts the brain to send out alarm signals telling the body that it is starving and that the person should eat as many calories as possible in order to survive. At the same time, the brain is also telling the body to conserve as much energy as possible, in part by – you guessed it! – being more sedentary. The hypothalamus responds via the vagus nerve to prompt the release of more insulin from the pancreas, further compounding the issue by increasing the risk of insulin resistance.
In a healthy system, insulin production increases after a meal so that the body can transport glucose from the blood into cells for use as energy. When a person is resistant to leptin, this leads to chronic increases in insulin as part of the body’s attempt to store more and more energy (Kolaczynski et al., 1996). Insulin also appears to block leptin receptors in the brain, creating a cyclical problem (Imbeault et al., 2001).
By default, the body’s system is set to store and conserve energy, a process which served us well in the past. From an evolutionary point of view, storing energy in fat cells was crucial for survival as it helped our ancestors maintain their strength and survive for longer when food was scarce and calorie intake irregular.
However, given that most of us have almost constant access to high calorie food, a system that is set to store fat and encourage us to keep eating can rapidly lead to dramatic weight gain.
In people with leptin resistance, not only is the body sending out panic signals telling them to keep eating, it also acts via the sympathetic nervous system to tip the body into conservation mode, promoting lower energy expenditure and physical activity. And the comfort of the office chair provides just that. This is one of the reasons why people with diabetes, as well as those who are inactive and/or overweight, are more likely to experience depression and greater effects from stress and lethargy.
Leptin also follows a circadian rhythm that is in direct opposition to the daily peaks and troughs of cortisol, the ‘stress hormone’ (Froy, 2010). Levels of leptin drop in the morning (prompting us to eat), reach their lowest point around noon, and then rise in the evening to reach their highest after midnight. In contrast, cortisol levels are typically highest in the morning and drop in the evening, helping us feel active during the day and relax at night. Poor stress management and a disturbed circadian rhythm can wreak havoc on our natural leptin cycle. This explains why it can be harder to manage appetite if we experience sleep deprivation, work night shifts, have jet lag, or are exposed to blue light from screens and interior lighting after the sun has set. For many, this will sound all too familiar. Furthermore, this disruption explains why appetite and motivation can suffer when we experience a high level of daily stress with no opportunity for an adequate physical response, i.e. no chance for fight or flight. And the situation only becomes more dire as, the next day, the cycle continues.
In recent years, researchers have discovered that leptin doesn’t solely engage the hypothalamus for energy homeostasis. The hormone also interacts with the dopaminergic system in the brain. Dopamine has many functions and is our main ‘reward’ neurotransmitter, driving motivation and willpower. Dopamine also plays an important role in memory, focus and mood. Dysfunction in the dopaminergic system can lead to neurodegeneration, mood disorders, and is associated with psychiatric conditions such as schizophrenia. The dopamine pathway is also the main target in drug addiction.
Leptin also has a role to play in the dopaminergic system, by promoting balance. When it is functioning correctly, leptin signals to the brain that we have enough energy, from either food intake or fat reserves. It does this by extinguishing the dopaminergic reward pathway. However, this mechanism does not work properly in a person with leptin resistance, which means that they are driven to continually seek more rewards by consuming; for many this means more sugary or fatty foods. This same mechanism is at work in drug addiction, where brain dopamine receptors become desensitised over time, prompting the individual to seek increasingly intense stimuli to achieve the same level of reward response.
YOUR BRAIN ON DOPAMINE – WHO’S IN CHARGE?
Beyond maintaining a healthy level of food intake, dopamine is also key to regulating physical activity. Damage and dysfunction in the dopamine system have been linked to movement disorders such as Parkinson’s disease, as well as to addictive behaviour, depression, and sedentary behaviour. Dysfunctional dopamine receptors lead to anergia, i.e. a shift to low effort options for reward. This has been demonstrated in animals, with studies showing that mice with depleted dopamine levels spend less time engaged in high-effort exercise activities (like running in a wheel) and are instead more likely to choose low-effort rewards such as sucrose treats (López-Cruz et al., 2018). Post-mortem studies of brains of individuals who were overweight have also revealed significant dysfunction in the dopaminergic system, leading researchers to suggest that a dopamine reward deficiency syndrome may underlie abnormal eating and exercise behaviour that can lead to obesity (Wu et al., 2017).
In recent years, researchers have found that a certain kind of dopamine receptor (D2) in the basal ganglia area of the brain is less active in those who are overweight (Ruegsegger & Booth, 2017) and continued weight gain seems to progressively dull D2 dopamine receptor activity (Kravitz et al., 2016). In practice, this means that an overweight person is less likely to experience ‘runner’s high’ – the pleasurable reward response many people feel during and following exercise – which means they may feel less inclined to begin exercise in the first place.
It is important to distinguish that reduced sensitivity to dopamine does not cause a person to gain weight. Rather, the state of being overweight may make people feel less motivation to exercise, leading to a further sedentary lifestyle and increased weight gain. Another vicious cycle. Less exercise leads to more weight gain, more leptin resistance, and more dopamine receptor dysfunction, all which further decreases our motivation to stop sitting and start moving. Once you understand the underlying mechanisms at play, it’s not hard to see how a person who is mostly sedentary can enter into a downward spiral resulting in obesity and a host of associated issues.
There is also evidence that exercise-induced increases in dopamine signalling can lead to increases in brain-derived neurotrophic factor (BDNF), which we will discuss at length in the next chapter. This protein supports healthy neuron growth in the brain, maintaining what is called neuroplasticity. Basically, BDNF helps the brain rewire itself, so we can continue to learn new things and stay flexible in our thinking. Part of this includes helping us better regulate our appetites and adopt healthier dietary and lifestyle habits for successful weight management (Ferris et al., 2007; Pelleymounter at al., 1995).
These recent insights into the dopaminergic system strongly suggest that it’s unfair to assume that overweight individuals all just lack the willpower and motivation to exercise more and eat less. Instead, it appears increasingly likely that the brain itself can scupper our best intentions by making exercise seem like far too much effort for far too little reward. These same changes in the brain may make it more likely for us to derive greater pleasure from things that require little effort, such as eating foods high in sugar and fat and seeking comfort by spending the day off our feet (Ruegsegger & Booth, 2017).
The good news is that exercise not only helps enhance insulin sensitivity for improved energy metabolism, it can also make the brain better respond to dopamine. Switching sedentary behaviour for physical activity helps to increase dopamine receptor availability in people with D2 receptor dysfunction, actually making them more likely to want to keep exercising (Robertson et al., 2016). Regular exercise, a healthy diet, and moderate weight loss can help ‘reboot’ dopamine receptors. This leads to improvements in dopamine levels and dopamine response, helping people who are overweight actually enjoy exercise, while simultaneously supporting improved appetite regulation. Now this is a good cycle to fall into!
SHOULD WE JUST WALK MORE?
Based on a number of studies, the short answer is a resounding yes. First off, walking creates a great opportunity for breaking out of this de-motivation trap. One study found that people with early stages of Parkinson’s disease (a condition characterised by decreased dopamine) who walked on a treadmill three times a week for eight weeks had improvements in dopamine receptor response compared to patients who didn’t use the treadmills (Fisher et al., 2013).
Not only is low-intensity exercise, such as walking, effective for supporting insulin sensitivity and overall energy metabolism, it also appears to enhance our ability to feel good about making healthier lifestyle choices. Good decisions yield good decisions. Walking is also a good choice for many because it puts less strain on the joints than other more intense forms of exercise. This means that people are less likely to experience walking-related injuries that hinder their attempts to lose weight through exercise.
Studies show that most of us gain around one kg (2.2 lbs) a year in middle-age. While this may not initially seem like a huge difference, it quickly adds up over time! Luckily, we are able to avoid most of this weight gain by walking more. The protective effect of walking has even been seen in people who don’t perform other types of exercise, i.e. people who just walk are more likely to avoid weight gain in middle age compared to those who hit the gym a few times a week but are otherwise sedentary. (Gordon-Larsen et al., 2009).
Today, it is abundantly clear that walking can be a great way to break free from the vicious cycle outlined above and instead create a positive feedback loop that supports healthy weight management, better cardiovascular and cognitive health, and a generally happier outlook on life.
WALKING THE WEIGHT AWAY
For anyone struggling to lose excess body weight and get into a positive exercise routine, it helps to start out small and gradually integrate more movement into daily life. This might mean going for a short (15 minute) brisk walk after meals.
The aim should be to increase walking time by 1,000-1,500 steps a day (something most people can achieve in around 15 minutes), and build up to 15,000 steps daily. This number can seem daunting for those trying to establish a regular exercise program, but breaking this target number down into smaller step goals each week and celebrating continual successes can help maintain motivation. There are a number of apps and fitness trackers out there designed to do just that.
Walking throughout the day is preferable to spending most of the day sitting and trying to offset that with a single burst of exercise. All those steps quickly add up, and by spending less time sitting, the brain and body begin to respond more favourably to exercise, meaning that it becomes easier and easier to maintain a healthy walking regimen and regulate appetite.
About the Author
Eric Soehngen, M.D., Ph.D. is a German physician and specialist in Internal Medicine. With his company Walkolution, he battles the negative health effects that sitting has on the human body. Walkolution develops ergonomically optimized treadmill desks, which help to bring more movement into the daily work routine in the office or home office.
Photo credit: Sharon McCutcheon