Dr. Gijs Goossens is an Associate Professor at the Department of Human Biology (NUTRIM School of Nutrition and Translational Research in Metabolism), Maastricht University Medical Centre, The Netherlands. His main research focus is the role of adipose tissue dysfunction in the pathophysiology of obesity-related insulin resistance in humans, thereby integrating well-controlled human metabolic in vivo studies, analyses in adipose tissue and skeletal muscle biopsies, and mechanistic in vitro experiments using human primary adipocytes and myotubes. He is one of the pioneers in the field of adipose tissue and skeletal muscle oxygenation in relation to metabolic impairments in humans. For his work, he has received several prestigious awards, including the Young Investigator Award in Clinical Research from the European Association for the Study of Obesity (2011) and the Rising Star Award from the European Foundation for the Study of Diabetes (2014). Dr. Goossens has served as a Board member of EASO’s New Investigators United (2010-2016), is President of the Netherlands Association for the Study of Obesity (NASO), and Co-chair of the Scientific Advisory Board of the European Association for the Study of Obesity. He is also the local Chair of the joint EASO/IFSO-EC congress that will take place in Maastricht in 2022.
Dr Gijs Goossens, thank you for speaking with us and congratulations on the publication of your recent article The Metabolic Phenotype in Obesity: Fat Mass, Body Fat Distribution, and Adipose Tissue Function http://www.karger.com/Article/FullText/471488 which ranks among the highly cited publications in Obesity Facts.
Thank you. I find it really important that an article is widely read, used and/or cited by colleagues in the field. So, it is very nice to hear that this article ranks among the most-cited publications in Obesity Facts.
In Europe, obesity is typically defined by the default measure, BMI. What is your view?
The body mass index (BMI) is used for classifying obesity (BMI≥30 kg m-2). This surrogate marker for fat mass is positively associated with risk factors for cardiovascular and metabolic diseases at the population level when BMI is above 18.5 kg m-2. Importantly, BMI is not an accurate measure of body fat mass and health status of an individual, since it does not take body composition (i.e. skeletal muscle mass) into account. The use of BMI as an indicator of cardiometabolic health is even more problematic in older obese persons with decreased muscle mass, i.e. sarcopenic obese patients, who are at special risk for adverse outcomes. Currently, more sensitive techniques to determine body composition are available, and phenotyping beyond BMI is clearly needed to accurately assess metabolic health at an individual level.
Can you summarise the argument about “healthy obesity” and share your perspective?
It is rather fascinating that expansion of adipose tissue does not necessarily translate into metabolic abnormalities. A subset (~10-30%) of people living with obesity seems to be relatively protected against worsening of metabolic health. This group of individuals, characterized by the absence of metabolic disturbances such as dyslipidemia, insulin resistance, impaired glucose metabolism and overt type 2 diabetes is often referred to as ‘metabolically healthy obese’ (MHO). However, it can be debated whether MHO individuals are really healthy, since several recently performed meta-analyses of prospective cohort studies have shown that the majority of MHO individuals has a markedly increased risk of developing type 2 diabetes and cardiovascular disease over time compared to healthy, normal weight individuals. Not less important, MHO individuals may also have a lower quality of life than normal weight individuals because of other comorbidities.
Interestingly, several studies have shown that MHO have a better adipose tissue function, store less fat in skeletal muscle and the liver, and are more insulin sensitive than metabolically unhealthy people living with obesity. These findings highlight the central role of adipose tissue function in cardiometabolic health in humans.
How does body fat distribution impact adipose tissue function and insulin resistance?
Although total fat mass is a more accurate measure of the metabolic phenotype than BMI, the absolute amount of body fat does not unambiguously reflect metabolic health at the individual level. This is exemplified by the finding that abdominal liposuction (the surgical removal of subcutaneous adipose tissue in the abdominal region) does not significantly improve obesity-associated metabolic abnormalities such as insulin resistance. Likewise, certain pharmacological interventions improve insulin sensitivity and, therefore, glucose homeostasis in humans, despite significant fat mass gain.
Body fat distribution is a strong metabolic and cardiovascular risk factor In other words, the location where (excessive) calories are stored seems one of the key factors that predisposes towards obesity-related cardiometabolic complications. Accumulation of adipose tissue in the upper body (abdominal region) is associated with the development of obesity-related comorbidities and even all-cause mortality. In contrast, population studies have shown that accumulation of fat in the lower body (on the hips and thighs) is associated with a protective lipid and glucose profile, as well as a decrease in cardiovascular and metabolic disease prevalence, taking total body fat mass into account. Indeed, premenopausal women living with obesity, who on average have a more ‘pear-shaped’ body fat distribution pattern (more gluteofemoral adipose tissue), have a lower risk of developing cardiometabolic diseases compared to age- and BMI-matched men. The reason for these discrepancies in disease risk seems related to differences in adipose tissue function between these fat depots. More specific, fat depot-differences in adipose tissue expandability, fat cell enlargement, adipose tissue lipid metabolism and local inflammation seem to contribute to inter-individual differences in disease risk in people living with obesity. The mechanisms underlying inter-individual differences in body fat distribution are not yet fully understood. This is an important topic of current investigations.
What do you see as the benefit of developing more detailed metabolic phenotyping of people with obesity?
Detailed metabolic phenotyping of people living with obesity will be invaluable in understanding the pathophysiology of metabolic disturbances, and is needed not only to identify high-risk individuals or subgroups, but also to pave the way for optimization of prevention and treatment strategies to combat obesity-related complications. For example, not all people living with obesity will benefit to a similar extent from certain dietary interventions, exercise programs and/or pharmacological approaches. The challenge is to find good biomarkers that enable us to provide optimal care for people living with obesity. Importantly, since obesity is a complex, multifactorial chronic disease, a holistic approach of tackling obesity from prevention (of further weight gain and/or complications) to treatment and aftercare is needed, with involvement of different healthcare professionals.
https://www.karger.com/Article/FullText/471488 DOI: 10.1159/000471488