Professor Gijs Goossens, who was recently promoted to full professor of Cardiometabolic Physiology of Obesity at Maastricht University, the Netherlands, recently appeared in a thirty minute segment on the Dutch national television science program "Focus”. In the program, which can be accessed through the link below, he discusses the complex pathophysiology of obesity, and explains how dysfunctional adipose tissue contributes to obesity-related complications. He elaborates on the limitations of using BMI as the sole measure of obesity, the challenges of maintaining body weight following weight loss, and potential determinants of weight regain over time. The interview also covers important topics like weight bias and obesity stigma, and provides insights into the latest developments in obesity medications, including their role and effectiveness in obesity management.
Congratulations on your promotion to full professor! Can you share with us how your journey in the field at Maastricht University began and what inspired you to pursue the physiology of obesity as a field of study?
Thank you. Since my undergraduate studies, I have been interested in the complex relationships between obesity and chronic diseases. As a graduate student, I was involved in a study aimed at investigating the importance of intramyocellular lipids, measured using in vivo proton magnetic resonance spectroscopy (1H-MRS), in glucose homeostasis in humans. Thereafter, I was convinced that I wanted to pursue a PhD. Yet, I decided to first acquire more experience with metabolic research abroad. During an inspiring 7-month internship at the University of Oxford (UK), I was fortunate enough to be able to work together with leading experts in adipose tissue physiology (Profs. Fredrik Karpe and Keith Frayn). I became fascinated by the pivotal role that fat tissue plays in health and disease. Thereafter, during my PhD project at Maastricht University (2002-2006), my interest in how perturbations in metabolism and inflammation drive cardiometabolic complications in obesity grew further, as did my skills to metabolically phenotype humans using state-of-the-art in vivo methodology. The overarching goal of my translational research is to better understand the mechanisms underlying adipose tissue dysfunction and cardiometabolic impairments in people with obesity, with the aim to establish more personalized, effective lifestyle and pharmacological interventions to improve cardiometabolic health. It has been my ambition to contribute to healthy ageing and improved quality of life of people living with obesity.
You have been part of this community for a long time, Gijs. As an expert in the biology of obesity, what are some of the most significant changes or advancements you have witnessed in the study of obesity and its impact on cardiometabolic health since you were a student and early career researcher first involved in the EASO community?
We have learned a lot about obesity over the past few decades. When focusing on the biological aspects of obesity, I have witnessed and also contributed to several important advances in our understanding of the biological processes taking place in the adipose tissue, and how these change during the development of obesity. The adipose tissue was initially viewed as an inactive organ responsible for the storage of excessive energy, providing insulation, and cushioning vital parts of the body. However, this view has drastically changed upon the discovery of the endocrine function of the adipose tissue about 30 years ago. Through the release of fatty acids and the production of various so-called adipokines, including leptin and several pro-inflammatory factors, the adipose organ is able to communicate with other tissues (that is, inter-organ crosstalk). It is now well established that the adipose tissue plays a central role in the regulation of many physiological processes. Importantly, the development of obesity has a major impact on the adipose tissue. Not only does it lead to an increase in its mass, obesity also drives detrimental changes in the composition and function of this key metabolic organ. Adipose tissue expansion caused by weight gain leads to the infiltration of various immune cells such as macrophages. Together with fat cell enlargement to accommodate fat mass expansion, this influx of immune cells leads to a chronic inflammatory response and metabolic perturbations in obesity.
Furthermore, it has become increasingly clear that obesity is not a homogeneous entity but a very heterogeneous disease. There are individuals with obesity that are relatively protected against the detrimental effects of excess adiposity on cardiometabolic health. Likewise, responsiveness to interventions differs between individuals with obesity, which means that more personalized approaches are required to increase the effectiveness of certain interventions.
Balancing a demanding professional life with personal interests can be challenging. I think everyone who knows you is aware that you enjoy sports activities like running, cycling and strength training. Could you share some insights on balancing a rigorous research and teaching schedule and your volunteer commitment within EASO as co-chair of the Scientific Advisory Board with the demands of family life and the other activities you enjoy?
In general, it helps to have a strong desire to achieve things. I feel motivated when contributing to a common goal, and that is also why I also enjoy to be part of (inter)national scientific societies and committees/boards, like EASO, where I have the privilege to be the co-chair of EASO’s Scientific Advisory Board. At the same time, I try to maintain a healthy balance between work and personal life, although I must admit this is not always easy. But I have a fantastic wife and two beautiful daughters, who help putting work in perspective. I think that a meaningful life encompasses various dimensions beyond professional achievements. In my opinion, personal happiness propels career aspirations. For me, being physically active and working out contributes to personal happiness, and helps creating a good balance between work and social life.
Has there been a pivotal moment or a key mentor in your career who significantly influenced your path? How did this contribute to your professional development?
It is difficult to mention just one person. I learned a lot from many people over the years. During my stay as a visiting scientist at the University of Oxford, Profs. Keith Frayn and Fredrik Karpe were great mentors, demonstrating that excellent science can take place in a friendly and supportive working environment, paying attention to all lab members. This is also what I try to keep in mind when leading our team at Maastricht University. During my PhD, I was privileged to be supervised by key opinion leaders in the field of human energy and substrate metabolism, namely Profs. Wim Saris, Marleen van Baak and Ellen Blaak. They have introduced me to the field of obesity as well as to several leading experts in our field of research. I am still very grateful for that, as well as for giving me the opportunity to develop my own research lines.
In your recent interview on the science programme “Focus” on Dutch national television, you discussed the complexity of obesity beyond traditional perspectives around obesity as a product of individual behaviours in diet and exercise. Could you elaborate on some common misconceptions about obesity and how your research addresses these misconceptions?
It is well established that obesity is a multifactorial chronic disease that acts as a gateway to many other non-communicable chronic diseases. A common misconception is that obesity is always the result of an unhealthy lifestyle, that it is the result of a lack of discipline, that someone with obesity is ‘just lazy’, that it is a person’s own fault. To be clear, it is well established that obesity is often the result of a complex interplay between genetic, metabolic, socio-economic, behavioral and environmental factors that override the physiological mechanisms involved in body weight regulation. Thus, obesity and its complications should be prevented and treated using a holistic approach, taking these different factors into account, involving different healthcare professionals. Since the causes of obesity and related complications can differ between individuals, not all people living with obesity will benefit to a similar extent from certain dietary interventions, exercise programs and/or pharmacological approaches. We try to obtain a better understanding of the mechanisms underlying inter-individual differences in obesity-related cardiometabolic complications, which will allow the development of more effective prevention and treatment strategies to achieve more pronounced improvements in health and wellbeing.
You emphasized the importance of looking beyond Body Mass Index (BMI) in understanding obesity. What are some alternative approaches or measurements that you believe offer a more comprehensive understanding of this condition?
Although the use of BMI has retained its value in epidemiology, this anthropometric surrogate measure of adiposity does not accurately reflect body fat mass and the health status of an individual, and does not seem a good predictor of morbidity and mortality risk at an individual level. For example, the use of BMI as an indicator of cardiometabolic health is problematic in older individuals who are characterized by decreased muscle mass (that is, sarcopenic patients with obesity). Research has demonstrated that body fat distribution and adipose tissue function are key determinants of obesity-related complications, yet this is not taken into account when using BMI. Therefore, phenotyping beyond BMI is needed to accurately assess the health status of an individual. Since abdominal obesity is associated with an increased risk of developing chronic cardiometabolic diseases, measurement of the waist circumference and/or the waist-to-height ratio provides important additional information, beyond BMI, about the health status of an individual.
The broadcast highlighted the challenges people face in maintaining weight loss over the long term. In your view, what are the key factors that contribute to this difficulty?
The most beneficial way to revert obesity-associated complications is losing body fat, which can be effectively achieved through caloric restriction. In addition to loss of fat mass, however, body weight loss is also accompanied by a reduction in muscle mass. Muscle mass is a key determinant of energy expenditure. Therefore, weight loss is paralleled by a decrease in energy expenditure. Furthermore, metabolic adaptation (that is, a reduction in energy expenditure beyond what can be expected based on changes in body composition) and changes in feelings of hunger and satiety are observed following weight loss. Together, these factors, amongst others, make it very hard to maintain body weight following weight loss in the long term.
Regarding the latest developments in obesity medications, how do you see these treatments evolving, and what role do they play in the broader context of obesity management?
Significant health improvement can be achieved with a healthy diet and sufficient physical activity. In case lifestyle is not optimal, lifestyle adjustments are an important first step to prevent or reduce complications in people with obesity, even when modest weight loss is achieved. But a lifestyle intervention may not result in sufficient weight loss and health gains. Sometimes this is because someone, for whatever reason, is less likely to follow the advice regarding diet and/or is less able to be more physically active (i.e., in case of joint complaints). In other cases, despite significant weight loss and some health improvements following lifestyle intervention, a person still has a substantially increased risk of obesity-related complications. It is great that obesity medication is now available for certain patients with obesity due to important scientific developments. Obesity medication, however, should not be seen as a ‘quick fix’. Further research is still needed to better understand the mechanisms of action as well as inter-individual variation in pharmacological treatment responses, and to investigate whether the beneficial effects of obesity medication are maintained in the long term. It may not be the solution for everyone with obesity, but it certainly will be a valuable addition to a healthy lifestyle. For sure, the availability of obesity medication will contribute to better obesity management.
Looking forward, what are some emerging trends or areas of research in cardiometabolic physiology that you find particularly promising?
Although weight loss is the most effective way to curtail cardiometabolic complications in people with obesity, this is often followed by weight regain, as mentioned earlier. The extent of this problem is illustrated by results from various studies, demonstrating that about 20% of individuals is able to remain weight stable 1 year after weight loss. On average, more than 50% of the initial weight loss is regained after 2 years and more than 75% of the weight loss is regained within 5 years. Although various initiatives have been launched aimed at preventing obesity-related diseases, the harmful effects of weight cycling have been largely overlooked. Furthermore, current lifestyle and pharmacological interventions aimed at weight loss and, even more important, the prevention of weight regain following weight loss often ignore the heterogenic nature of obesity. Despite the high frequency of weight cycling coupled to the severe cardiometabolic and psychological complications associated with weight cycling, the underlying mechanisms and thus effective approaches to prevent or minimize weight regain and worsening of cardiometabolic health have remain unknown. Moreover, understanding of the inter-individual variation in (the rate of) weight regain and body weight cycling is lacking, thus hampering the development of more personalized approaches to improve cardiometabolic health and, related to this, quality of life in patients living with obesity. A better understanding of the interplay between biological, psychological, environmental and behavioral factors in the etiology of obesity and its complications will lead to more personalized approaches to prevent and treat obesity-associated cardiometabolic complications, going beyond the ‘one-size-fits-all’ approach that is currently often used.
Finally, based on your extensive experience and research in the field, what advice would you give to a student or early career professional just beginning their journey in the field?
Don’t be afraid to be ambitious about your goals, and don’t let other people belittle your ambitions! If you don’t have enough ambition, you might have trouble achieving your goals or experiencing growth. However, if you have too much ambition, you may be at risk of too much stress and burnout. Therefore, my advice would be to try to accept that a scientific career requires patience and perseverance. Finding satisfaction, a sense of accomplishment, at every step of your career is important. Celebrate successes, no matter how small! I truly believe that one can make much more progress if you love what you are doing, and let your ego go, since science is team work. Never regret a decision, and realize that it is always possible to redirect your career in the future. I hope to motivate and inspire young students to pursue an academic career, and enjoy training new researchers. There are many scientific and societal challenges ahead. We need talented new researchers to advance the field of obesity research, thereby contributing to the prevention of obesity and its complications, better care and improved quality of life of patients with obesity.
Here is a link to view the broadcast: https://npo.nl/start/serie/focus/seizoen-5/focus_16/afspelen