Heart failure and obesity: the Medical University of Graz investigates the link

Everyone is aware of the heart’s role as a vital organ. The muscle pumps blood through the body, thereby ensuring that all organs and tissues are adequately supplied with oxygen and nutrients. When the heart’s function is impaired, this is referred to as heart failure. The causes of heart failure are varied and range from heart attacks, high blood pressure and heart valve diseases to congenital heart defects or hormonal disorders. At the Medical University of Graz, the risk factor of being overweight and its effects were investigated.

Heart failure

In Austria alone, around 300,000 people live with heart failure, with about half of them suffering from the form known as heart failure with preserved ejection fraction (HFpEF). In HFpEF, although the heart’s pumping power remains intact, a stiffened muscle prevents the heart from filling sufficiently with blood to perform its function optimally. The consequences, particularly during physical exertion, include shortness of breath, reduced physical performance and a dramatic decline in quality of life – as well as a mortality rate of over 50 per cent within five years of the initial diagnosis. 

HFpEF is one of the most common causes of hospital admissions among patients over the age of 65. Due to demographic change, the number of people with heart failure is steadily increasing. HFpEF poses a significant challenge, as there are only limited treatment options, due to insufficient research and mechanisms that are not yet fully understood. 

However, HFpEF is not ‘just’ a heart condition, explains Simon Sedej: ‘HFpEF is a systemic disease that affects the entire body. It arises primarily from the interaction of ageing, physical inactivity and associated metabolic disorders such as overweight or obesity, high blood pressure and metabolic syndrome. These conditions, which are among the greatest risk factors for HFpEF, lead to a vicious circle of metabolic derailment and progressively impaired heart function.”

The paper ‘Inhibition of Adipose Tissue Lipolysis Treats Obesity-Related HFpEF’, published in the journal *Circulation Research*, examines the role of obesity in the treatment of HFpEF. Lead author Alina Stockner is delighted with the results: “Adipose tissue does indeed play a central role in HFpEF by contributing to the development of chronic systemic inflammation. Despite the significant role of adipose tissue in the course of the disease, there is currently no evidence that direct modulation of adipose tissue metabolism alone is sufficient to treat obesity-associated HFpEF. In this study, we provide compelling evidence that the genetic or pharmacological inhibition of lipolysis specifically in adipose tissue is sufficient to prevent or treat obesity-associated HFpEF.”

Focus on atglistatin

The research centred on a substance called atglistatin. It specifically inhibits adipocyte triglyceride lipase, a key enzyme in fat metabolism. The study demonstrated that the use of atglistatin has a more effective positive impact on cardiac function in a mouse model of HFpEF than dietary calorie restriction alone. Furthermore, it was shown that important pro-inflammatory mediators such as IL-1β, which promote the progression of heart failure, can be reduced by atglistatin. The researchers believe that these findings will help to initiate further studies into the inhibition of lipolysis in HFpEF, thereby contributing to improved treatment for obese patients.

Profiles: Alina Stockner and Simon Sedej 

Alina Stockner completed a Bachelor’s degree in Molecular Biology at Graz University of Technology, followed by a Master’s degree in Biochemistry and Molecular Biomedicine. She is a PhD student in the Molecular Medicine programme.

Simon Sedej is an associate professor of cardiac physiology and, as a group leader at the Medical University of Graz, conducts research into the mechanisms of aging in the heart and innovative therapeutic approaches for the treatment of age-related heart failure. Over the past three years, he has led the European research consortium ‘MINOTAUR’, funded by the FWF and the EU, which involved experts from Austria, France, Portugal, Spain and Germany. The clinically relevant findings of his research group, which is based at the university’s Heart Centre, have been regularly published in high-impact scientific journals in recent years and have been recognised with prestigious awards.