Weighty questions.
Text: Santina Russo
An increasing number of people are severely overweight. Researcher and physician Professor Katharina Timper is on the case, offering consultation and treatment for patients at the obesity outpatient clinic at University Hospital Basel. She often finds herself correcting misconceptions.
Fifty years ago, just over three percent of the world’s population was obese, defined as having a body mass index (BMI) of over 30 kg/m2. Today, that number has already reached 13 percent. In Switzerland, the percentage of people living with obesity has more than doubled over the past 25 years. Now, nearly one in ten is affected by the condition. Severe obesity is a risk factor for cardiovascular diseases, type 2 diabetes, dysregulation of blood lipid levels, known as dyslipidemia, cancer and even dementia. But what causes obesity and how can we treat it?
Is obesity a lifestyle choice or a disease?
Obesity is a disease controlled by both inherited and acquired factors. It is caused in part by faulty signaling in the brain, more specifically in the hypothalamus, which is one of the most important centers for regulating energy balance and food intake. In the hypothalamus, specialized neurons receive signals from the periphery of the body and pass on these signals to downstream neurons located in other regions of the brain. There, they feed into finely tuned processes that regulate glucose metabolism and satiety as well as energy expenditure. Innumerable cells, receptors and chemical messengers are involved in these processes, so there are also endless opportunities for error. If certain synapses do not fire correctly or if certain receptors are not functioning properly, this can result in obesity. Errors such as these can be genetic, that is inherited, or they may be acquired, for example as a consequence of environmental factors or living conditions. It is also important to note that environmental influences can even change the way genes are expressed.
How much do the processes in our brains affect how we eat?
There is a very strong connection here. Experiments on mice demonstrate that very clearly. We can genetically modify certain neurons in a mouse’s brain so that they can be activated via laser. When the laser is switched on, the mouse eats, and when it is switched off, it stops. Switch it on again, and the mouse starts eating again. The organism is powerless to resist this command from the brain.
The effect is similar for us humans: Our desire to eat is controlled by processes within the brain apart from voluntary control. That is just another reason why our assumptions about obese people, particularly those promulgated by healthcare practitioners, are unjustified and extraordinarily destructive and dangerous. In truth, the stigma faced by patients affected by obesity is not only caused by the condition – it is a significant contributing factor to weight gain in the first place. Experiencing constant denigration from others negatively impacts self-image, promoting emotional eating, further weight gain and social isolation. That is why it is so important for us to reconsider the issue and address the biological underpinnings of this disease.
To what extent is obesity genetically predetermined?
Inherited factors certainly play a decisive role here. We are aware of a few genes that can cause obesity given specific mutations. Add to that the myriad of other genetic factors that we know nothing about or that we are only just beginning to understand. «Epigenetic factors» are also key. Epigenetics is the mechanism by which the activity of a gene is modified by external factors. For example, the mother’s eating patterns during pregnancy and breast feeding affect the child’s food choice and eating habits as revealed from rodent studies.
How can we treat obesity?
This is teamwork: with the patient and our interdisciplinary team at University Hospital Basel, we help patients change their lifestyle so that they can lose weight through a multidisciplinary therapeutic approach. Our therapy always includes dietary consultation and individualized exercise programs. Patients with depression or those who struggle with emotional eating benefit from coaching by our colleagues specialized in psychosomatic medicine.
For patients who report that they eat very little, it often helps to measure daily energy expenditure, or basal metabolic rate. Many patients with obesity have an extremely low basal metabolic rate of little more than 1,000 calories per day. This metric makes it clear why it is so difficult for them to lose weight. We cannot change their basal metabolic rate, but we can help patients burn more calories by engaging in physical activity. That is why we offer a range of different athletic activities, from walking and swimming to trampoline. It helps group participants to train with other obese patients instead of the slim, athletic people they may otherwise see at the gym. It all comes down to this: The aim of the treatment is not to change the way our patients look. Our sole objective is to minimize risk factors and prevent patients from developing obesity-associated diseases.
When is it time to turn to drugs or surgical procedures such as gastric bypass?
These kinds of interventions are effective in supporting and consolidating lifestyle changes. We frequently prescribe a drug called Saxenda®, mimicking an endogenous hormone that increases the feeling of satiety. This can help patients who report feeling hungry constantly or those who struggle with emotional eating or binge eating. Many patients are finally able to lose weight and to maintain the lower weight for the first time in a stress-free manner, as they find that their thoughts no longer always revolve around their next meal. Surgical procedures are primarily of interest for patients with severe obesity and for patients who have already developed numerous comorbidities, including high blood pressure, sleep apnea or type 2 diabetes. The key is making sure these patients are well prepared for the surgery and for their life afterwards and providing close supervision following the procedure within a multidisciplinary, highly specialized team.
Sweets for the brain
Katharina Timper recently demonstrated that both neurons and another category of brain cells, known as astrocytes, play a role in controlling metabolic rates. Both types of cells have a receptor for the endogenous hormone GLP1, which served as the model for the obesity medication Saxenda. In trials on mice, Timper provided proof that deactivating this GLP1 receptor in the astrocytes led to changes in cellular metabolism. This initiated positive effects throughout the organism: The mice were not only better equipped to metabolize sugar, but they also demonstrated improved learning ability compared to the control group. «We discovered a connection between glucose metabolism and cognitive performance,» reports Timper. She and her research team at the Department of Biomedicine of the University of Basel are now investigating this link in greater detail.
Katharina Timper is a professor and research group leader at the Department of Biomedicine as well as chief of service physician and head of the obesity outpatient clinic at the Department of Endocrinology, Diabetology and Metabolism at University Hospital Basel.
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