Lecture Overview

In recent years, the remarkable progress of GLP-1 receptor agonists has made it possible to treat obesity medically. These agents, which demonstrate significant weight-reducing effects, are expected to become central to obesity treatment, much like statins in the management of dyslipidemia. However, from the perspective of long-term health promotion, some degree of obesity often remains even after GLP-1 receptor agonist therapy, indicating the need for further interventions. Therefore, elucidating the pathophysiology of obesity to develop treatments independent of the GLP-1 pathway remains a clinically important challenge.

In this presentation, I will discuss one example: the strong relationship between the metabolism of branched-chain amino acids (BCAAs—valine, leucine, and isoleucine) and obesity, which is widely known in general but not yet fully appreciated in clinical practice. These essential amino acids are metabolized in mitochondria and play a role in energy and heat production. Through clinical and basic research, I have demonstrated that impaired BCAA metabolism in brown adipose tissue, which is responsible for thermogenesis, reduces thermogenic capacity and thereby promotes obesity. Furthermore, we have found that gut microbiota partially regulate BCAA metabolism in brown adipose tissue. Based on these findings, this lecture will explore the potential for novel obesity treatments targeting BCAA metabolism.