New Clue in Obesity Treatment: Hormone Boosts Sympathetic Nerves to Increase Energy Expenditure

Professor Ji-Yoon Kim from the Department of Pharmacology at the Catholic University of Korea College of Medicine has identified a novel mechanism for the hormone GDF15 (Growth Differentiation Factor 15), which is gaining attention as a key clue in obesity treatment. GDF15 not only activates energy consumption but also promotes the growth and development of the sympathetic nervous system itself, thereby increasing energy expenditure.

 Professor Ji-Yun Kim and Chair Professor Myeong-Sik Lee of Soonchunhyang University's Biomedical Research Institute led the study as corresponding authors, with Research Professor Jin-Young Kim (first author) participating. This research was published in the 2025 edition of the international life sciences journal [Experimental and Molecular Medicine] (IF 12.9, a Nature sister journal). The paper is titled “GDF15 regulates development and growth of sympathetic neurons to enhance energy expenditure and thermogenesis.”

GDF15 has long been known as a hormone that suppresses appetite and stimulates the sympathetic nervous system to increase energy expenditure. Simply put, it was understood that GDF15 acts as the ‘accelerator pedal’ in the body's energy expenditure system.

However, in this study, Professor Kim Ji-yun's team newly revealed that GDF15 does not merely press the accelerator; it also plays a role in ‘building the engine itself’—that is, it promotes the growth and development of sympathetic neurons. The sympathetic nervous system is a neural network that regulates our body's energy expenditure. It sends signals to fat cells to generate heat (‘thermogenesis’) or cause energy consumption.

 The research team demonstrated through animal experiments that GDF15 increases energy expenditure by enhancing the density of sympathetic nerves within adipose tissue. Mice with overexpressed GDF15 showed increased sympathetic nerves in adipose tissue and improved ability to maintain body temperature. Conversely, mice lacking the GDF15 gene exhibited lower sympathetic nerve density and reduced energy expenditure.

 Furthermore, the research team discovered that the GDF15 receptor (GFRAL) is not only present in the brain, as previously known, but also in peripheral sympathetic ganglia. This finding suggests a new pathway through which GDF15 can directly participate in nerve growth without passing through the brain.

This study holds significant academic importance as it expands the function of GDF15 beyond ‘nerve activation’ to redefine it as a new concept: ‘regulation of nerve growth and development.’ This indicates that GDF15 acts as a key factor in enhancing long-term energy consumption efficiency not merely by sending signals that trigger energy use, but by redesigning and expanding the neural structures that transmit these signals.

 This discovery suggests potential for developing novel therapies not only for obesity but also for various metabolic disorders, including diabetic neuropathy and age-related sympathetic nerve damage. Particularly noteworthy is the identification of the GFRAL receptor, also present in the peripheral sympathetic nervous system. This discovery proposes a novel target strategy for drug development, moving beyond a ‘brain-centric approach’. It is highly significant as it presents a new approach to correcting the fundamental cause of obesity—energy metabolism imbalance—directly at the neural level.

 Professor Myeong-Sik Lee stated, “This research not only presents a new paradigm for obesity treatment but also opens a new research direction for treating metabolic diseases through structural repair of the nervous system,” adding, “If GDF15 can restore damaged sympathetic nerve networks, it could become a fundamental solution for diseases like aging and diabetes.”

 Professor Kim Ji-yoon emphasized, “Until now, GDF15 was thought to merely ‘turn on’ the energy consumption switch, but this study confirmed its role as a designer that strengthens the ‘wiring’ of the energy system. This could lead to the development of GDF15-based customized obesity treatments or nerve regeneration therapies in the future.” 

 This research was supported by the National Research Foundation of Korea (NRF) and the Korea Health Industry Development Institute (KHIDI).

△Professor Ji-Yun Kim, Professor Myung-Sik Lee, Research Professor Jin-Young Kim

△Figure caption: Schematic diagram illustrating the mechanism by which GDF15 regulates the growth and development of sympathetic neurons to enhance energy expenditure and thermogenesis.