Adipose tissue–Driven Atherosclerosis Mechanisms Across cliNical interventions and Translational models (ADAMANT) | 26CVD01

• Mikael RYDÉN, Karolinska Institutet (Sweden)
• Edward A. FISHER, NYU Grossman School of Medicine (USA)

Obesity increases the risk of heart disease, and weight loss is often recommended to lower that risk. However, keeping weight off long term is difficult for most people, even with newer weight-loss medicines. In real life, many individuals go through repeated cycles of losing weight and then regaining it. This pattern, called weight cycling, is common and may be harmful: growing evidence shows it can increase inflammation in the body and accelerate the build-up of fatty plaques in blood vessels (atherosclerosis), raising the risk of heart attack and stroke. Yet current clinical practice does not fully account for how frequently weight cycling happens or how it may affect cardiovascular risk.

The ADAMANT network will study why weight cycling can be harmful and whether the way weight loss is achieved changes the impact on the heart and blood vessels. Our work is motivated by new findings, including unpublished results from our joint groups, suggesting that weight loss induced by newer medicines used to treat obesity and diabetes may reduce some of the harmful vascular effects seen after weight cycling by calorie restriction alone. We believe this difference may involve changes in fat tissue, which is not just a depot for energy storage but also releases signals into the bloodstream that can influence inflammation and blood-vessel health. To investigate this, we will combine studies in mice and pigs with detailed analyses of human blood and tissue samples. We will examine how weight cycling affects fat tissue, immune cells, and disease in blood vessels, and how different weight-loss strategies influence these changes. We will also search for markers in blood that can identify people who are especially vulnerable to the harmful effects of weight cycling, and those who may benefit most from specific weight-loss treatments. Our goal is to support safer, more personalized weight-loss strategies that protect long-term heart health in the real-world setting where weight cycling is common.