It is obvious that overeating leads to weight gain and enlargement of fat cells. But even with the same amount of intake, is there a way to prevent fat storage and promote its use as fuel?

The Jeonbuk National University (JBNU) research team reported in a leading international journal that inhibition of a specific protein in adipocytes can prevent obesity and enable development of a novel targeted therapy, drawing worldwide attention.

A collaborative research team from the JBNU School of Medicine, the School of Pharmacy and the Department of Surgery at Jeonbuk National University Hospital announced on the 15th that, in their latest paper in the international journal Nature Metabolism (20.8), inhibition of the protein p21-activated kinase (PAK4) prevents the body from storing fat and promotes its breakdown into free fatty acids for use as fuel.

The study was led by Professor Byung-Hyun Park of the JBNU School of Medicine and Professor Eun-Joo Bae of the JBNU School of Pharmacy, with participation from Jeonbuk National University Hospital, the School of Pharmacy at Sungkyunkwan University, the Department of Life Sciences at Seoul National University, and the research team from Voronoi Co., Ltd.

Within adipocytes, neutral triglycerides are stored in storage organelles called lipid droplets. These lipid droplets are surrounded by various proteins that allow the lipids to be broken down and release free fatty acids only when needed.

The protein FABP4 (fatty acid binding protein 4) in adipocytes is known to act as a carrier that binds released free fatty acids and transports them out of the cell, but how its function is regulated had not been studied.

The JBNU research team found that phosphorylation of a specific amino acid residue (Thr126) of FABP4 by the protein PAK4 prevents FABP4 from binding to the lipolytic enzyme HSL (hormone-sensitive lipase), thereby inhibiting HSL-mediated lipolysis. This finding is significant because it is the first identification of functional regulation of FABP4 in adipocytes and it suggests that PAK4 inhibitors could be a novel therapeutic target for obesity.

Professor Eun-Joo Bae of the JBNU School of Pharmacy said, 'By suggesting that inhibition of the protein PAK4 can serve as a new therapeutic target for obesity, we expect this research to provide a strong foundation for the development of obesity-related diagnostics and treatments.'

Meanwhile, this study was conducted as part of the National New Drug Development Project, the Mid-Career Researcher Program, and the Leading Research Center (medical and pharmaceutical field; MRC) support program, which are supported by the Ministry of Science and ICT, the Ministry of Trade, Industry and Energy, and the Ministry of Health and Welfare.