Weight Cycling and the Increased Risk of Atherosclerotic Cardiovascular Disease

• Applicant: Dr. Franziska Krautter
• Subject Area: Immunology
• Term: since 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 537302443

Cardiovascular disease is the major cause of death worldwide and atherosclerosis is the main pathology underlying heart attacks and strokes. While most therapies to reduce CVD focus on lipid lowering, there is a significant body of research providing evidence that targeting inflammation and lipid levels is more effective than lowering lipids alone. Obesity is one of the major risk factors of atherosclerotic cardiovascular disease and is thought to operate in part by promoting a systemic inflammatory state. Sustained weight loss has been a successful approach in improving obesity-associated inflammatory diseases, but in particular, weight regain after weight loss has been shown to have more detrimental effects on cardiovascular risk than sustained obesity. This is highly clinically relevant since the majority of people who lose weight regain it. Even though weight cycling has a big impact on cardiovascular health, the underlying mechanisms leading to improved inflammation during weight loss and the detrimental effects of weight regain are not fully understood. Previous studies have shown that weight cycling can induce epigenetic changes and innate immune memory in macrophages, the central cell of atherosclerotic plaques. This project aims to identify in established mouse models key epigenetic changes in macrophages and their progenitors induced by weight cycling and their effects on macrophage inflammation in atherosclerotic plaques. Furthermore, a phagocytic process called efferocytosis, which is a component of atherosclerosis resolution, is increased in atherosclerotic plaques after weight loss. Based on my preliminary data, part of my studies will focus on establishing the functional importance of a factor called Fcgr4 in macrophages for this increase. Overall, the results of the proposed project will uncover novel data on the molecular mechanism by which weight loss promotes atherosclerosis resolution and weight gain, its exacerbation.

• DFG Programme: WBP Fellowship
• International Connection: USA
• Host: Professor Dr. Edward A. Fisher