Matthias Blüher

Professor of Obesity Medicine

Helmholtz Institute for Metabolism, Obesity and Vasculature, Munich
Faculty of Medicine, University of Leipzig, Germany

Matthias Blüher is Professor of Obesity Medicine, Director of the Helmholtz Institute for Metabolism, Obesity and Vasculature research at the Helmholtz Center Munich and the University of Leipzig, Germany. He is Speaker of the Collaborative Research Center “Obesity mechanisms” at the University of Leipzig in Leipzig, Germany. Matthias Blüher´s research is focused on the role of adipose tissue function and distribution in insulin resistance, the development of obesity, type 2 diabetes and other metabolic and cardiovascular diseases.

Professor Blüher completed his medical studies at the University of Leipzig and his postdoctoral fellowship at the Joslin Diabetes Centre, Boston, USA. Matthias´ work has been recognized both nationally and internationally, as he is a recipient of the Obesity Research Award of the German Obesity Society 2003, the Ferdinand-Bertram-Prize of the German Diabetes Association 2008, the European Association for the Study of Diabetes (EASD) Rising Star Award (2010), and the Minkowski Prize of the EASD 2015.

Epigenetics – key factor underlying longevity and weight regulation?

Obesity is a chronic, progressive, not curable disease that is frequently characterized by relapse after short-term interventions. Through increased fat mass and adipose tissue dysfunction, obesity can contribute to multiple severe comorbidities. The fundamental cause of obesity is a long-term positive energy balance caused by too many calories consumed, too little physical activity and low energy expenditure. The pathophysiological origins of obesity are complex and include biological, societal, behavioral, environmental, economic and other factors and their interaction. Biological pathomechanisms of obesity development include inherited factors that modulate how the brain regulates appetite and satiety through complex and fine-tuned circuits in the hypothalamus. In addition, genetic and epigenetic factors may alter signals from adipose tissue, gut and other tissues that regulate periphery to brain crosstalk.

Although biological and societal factors represent the main drivers of the obesity pandemic, these factors are not able to entirely explain all cases of obesity and individual heterogeneous trajectories of the disease. Recently, it has been hypothesized that exposure to known and unrecognized obesogenic factors may play an underappreciated role in the development of obesity and epigenetic modifications may represent a key factor underlying weight regulation and longevity. In this context, the exposome refers to all influences over the whole life of a person of all the exposures and its relationship to disease. The obesogenic exposure of a person starts at conception and in utero, continuing over childhood and adolescence to adulthood. In contrast to the genome, the exposome is highly dynamic and variable throughout lifespan. Data derived from epidemiological studies linking excess weight with elevated ambient temperatures, in utero, and intergenerational effects as well as epigenetics, microorganisms, microbiota, sleep curtailment, and endocrine disruptors, among others, suggests the possibility that they may work alone or synergistically as several alternative putative contributors to the pathophysiology of obesity.

Here, data supporting the exosome hypothesis are summarized based on access to patients with metabolic abnormalities and extreme human phenotypes, including metabolically healthy obesity, monogenic obesity as well as longitudinal data (up to ~10 years after weight loss) and follow-up samples from patients who underwent sophisticated diet interventions (DIRECT, DIRECT-PLUS, CENTRAL) as well as a two-step bariatric surgery strategy. Using these interventions an increasing knowledge on epigenetic modifications, data are reviewed that suggest that epigenetics is a key factor underlying weight regulation and may define distinct obesity phenotypes. Epigenetic changes seem to prime cells for pathological responses in an obesogenic environment, contributing to the ‘yo-yo’ effect often seen with dieting. Targeting these changes in the future could improve long-term weight management, health outcomes and longevity.