KAIST has proposed a method to control metabolic diseases such as obesity and diabetes by altering metabolic energy metabolism within the body.
On the 1st, KAIST announced that a joint research team consisting of Professor Jae Myung Seo from the Graduate School of Medical Science and Engineering and Professor Dae Sik Lim from the Department of Biological Sciences identified a new therapeutic strategy for metabolic diseases.
The research teams elucidated and proposed a method to control metabolic diseases such as obesity and diabetes by inducing changes in metabolic energy metabolism within the body through activating adipocytes and reducing the physical size of adipose tissue by converting adipocytes back to their precursor stem cells (dedifferentiation), thereby promoting weight loss.
(From left) Professor Seo Jae-myung, Graduate School of Medical Science and Engineering; Professor Lim Dae-sik, Department of Biological Sciences; Dr. Choi Sung-woo, Graduate School of Medical Science and Engineering; Dr. Kang Joo-kyung, Department of Biological Sciences. Provided by KAIST
Adipose tissue serves as a "storage" for excess calories after meals in the form of fat and functions as an "endocrine organ" by secreting hormones. If either of these two roles malfunctions, our metabolic system collapses, leading to metabolic diseases such as obesity and diabetes. However, until now, the molecular-level mechanisms that harmoniously regulate these two functions were unknown.
In this context, the joint research team focused on the YAP/TAZ proteins of the Hippo signaling pathway and identified their functions related to adipocytes. They discovered that the activation state of YAP/TAZ proteins within adipose tissue changes depending on feeding status, that the activity of these proteins directly regulates the size of adipose tissue, and that YAP/TAZ directly participates in the production of leptin, a hormone that governs energy consumption and satiety.
The Hippo signaling pathway is an intracellular signaling system that plays a crucial role in determining the size of tissues and organs in multicellular organisms.
In particular, to elucidate the role of activated YAP/TAZ in vivo, the team specifically knocked out the LATS1/LATS2 genes in mouse adipocytes and confirmed that sustained activation of YAP/TAZ within adipocytes induces dedifferentiation of adipocytes into precursor cells similar to stem cells, thereby reducing the physical size of adipose tissue.
Reduction of body fat through dedifferentiation is a method distinct from existing approaches such as activation of brown fat focused on energy consumption or exercise.
Leptin is a hormone produced by adipocytes that suppresses appetite and increases energy expenditure, serving as a key regulator of metabolic systems. Its gene sequence was first identified 30 years ago. However, how leptin is produced and the molecular-level mechanisms involved had not been clarified.
This study is notable for being the first to reveal the transcriptional regulatory mechanism of leptin expression (the process regulating the creation of RNA from DNA) since the leptin gene sequence was identified in 1994. Furthermore, the research results suggest a new possibility of developing innovative obesity and metabolic disease treatments by increasing YAP/TAZ activity in adipocytes.
Meanwhile, this research was conducted with Dr. Sungwoo Choi (currently at the University of California, Berkeley) from the Graduate School of Medical Science and Engineering and Dr. Jukyung Kang from the Department of Biological Sciences as co-first authors. The findings were published online on May 29 in the world-renowned international journal Nature Metabolism.
The study was supported by the Ministry of Science and ICT’s Leader Researcher Support Project, Mid-career Researcher Support Project, Bio and Medical Technology Development Project, Overseas Outstanding Scientist Recruitment Project, and KAIST International Collaborative Research Support Project.
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