Title:
Chronic inflammation in cardiometabolic syndrome

Ichiro Manabe
Department of Cardiovascular Medicine, The University of Tokyo Graduate School of Medicine

Abstract:
Obesity has reached epidemic proportions around the world due to a modern lifestyle characterized by increased consumption of foods rich in energy and saturated fat, combined with reduced physical activity. Obesity, particularly visceral obesity, increases risks of non-communicable diseases (NCDs), including type 2 diabetes and coronary artery disease. It is increasingly appreciated that inflammation in obese visceral adipose tissue plays a key role in the development of systemic insulin resistance and expansion of chronic inflammation to multiple tissues. Inflammation in adipose tissue activates lipolysis, leading to increased release of free fatty acids (FFAs) to circulation. For instance, we found that FFAs activate inflammatory processes in the arterial wall and pancreatic islet, leading to neointima formation and b cell dysfunction. As such, the propagation of inflammation from obese adipose tissue to the cardiovascular and metabolic tissues, which is at least partly mediated by FFAs, is likely to be involved in development of atherosclerosis and type 2 diabetes. Recent studies have unraveling that various immune cells are involved in progression and suppression of inflammation in visceral fat. However, it is still poorly understood how homeostasis is maintained and inflammation is triggered by the immune cell network. We found that regulatory B cells and adipocyte progenitor cells are pivotal regulators of the initial activation of inflammatory processes. We also found that cellular interplays between cardiomyocytes, fibroblasts and macrophages are important for adaptive and maladaptive response of the heart to stress. In this talk I will discuss the cellular interplay and interorgan crosstalk in metabolic syndrome and heart failure.