Osaka Metropolitan University finds turmeric-derived compound blocks adipogenesis

A research group including Graduate Student Suzuna Araki and Associate Professor DongHo Kim of the Graduate School of Human Life and Ecology at Osaka Metropolitan University has revealed that a new compound, developed by modifying the turmeric-derived ingredient curcumin, suppresses the formation of adipocytes from its earliest stages. The group discovered that curcuminoid III, a structurally optimized curcumin derivative, significantly suppresses fat accumulation by directly controlling the early switch that determines whether adipocytes will form. This demonstrates the potential for a new obesity prevention method targeting the pre-fat formation stage, and expectations are high for its application as a new strategy for metabolic regulation utilizing food components.

The findings were published online in Nutrients. Concentration-dependent inhibition of adipogenesis by Curcuminoid IIIProvided by Osaka Metropolitan University Fat increases not only when existing adipocytes grow larger but also through adipocyte differentiation (adipogenesis), the process by which new adipocytes are created. Adipogenesis progresses through the step-by-step action of multiple transcription factors, and factors such as PPARγ and C/EBPα have been thought to play central roles.

On the other hand, the exact mechanism that determines the onset of differentiation in the very early stage, before these factors begin to work, remained poorly understood. Additionally, while curcumin, a component derived from turmeric, has previously been reported to suppress adipogenesis, many details regarding its precise mechanism of action and the relationship with its structure remained unclarified. The research group used multiple derivatives with modified curcumin structures to conduct a detailed, time-dependent analysis of their effects on an adipogenesis model using 3T3-L1 cells.

The results revealed that at a very early stage of adipogenesis (approximately 0.5 hours), curcuminoid III, which possesses a specific structure, increases the expression of KLF2, a transcription factor that acts to suppress adipogenesis. It was also shown that this change subsequently suppresses the expression of downstream differentiation-promoting factors such as PPARγ and C/EBPα.

Furthermore, it was confirmed that a broad range of central adipogenesis factors was suppressed during the middle stage of differentiation (day 3), and the expression of aP2, an indicator of adipocyte maturation, decreased during the late stage (day 7), ultimately inhibiting the formation of the adipocytes themselves. These results demonstrate that adipogenesis is not merely a continuous process, but rather a mechanism where "the overall progression is determined by regulation at the early stage." Although this study is a fundamental piece of research using cells, it provides an important clue for understanding how components contained in food regulate cell fate within the body.

In particular, these findings focusing on the early stage of adipogenesis could induce transition from the conventional post-differentiation approach to a new approach of controlling the process at the pre-differentiation stage. By advancing validation in animal models and humans, this work is expected to find applications as a new approach to prevent obesity and lifestyle-related diseases. Additionally, it will be necessary to evaluate the stability, metabolism, and bioavailability of curcuminoid III in vivo to verify whether it participates in regulating adipogenesis within a living organism.

Araki stated: "While carrying on the research of my predecessors and advancing the analysis in my own way, I was surprised to find that whether fat is formed is determined at a very early stage. The fact that a component contained in a familiar food possesses a mechanism that influences cell fate is deeply fascinating. I hope that these findings will develop into research that contributes to health maintenance and disease prevention in the future."

Journal Information Publication: Nutrients Title: Structure-Activity Relationship and Stage-Dependent Inhibition of Adipogenesis by Curcuminoid Derivatives in 3T3-L1 Cells DOI: 10.3390/nu18081285 Medicine Biology This article has been translated by JST with permission from The Science News Ltd. (https://sci-news.

co.jp/). Unauthorized reproduction of the article and photographs is prohibited.

This article has been translated by JST with permission from The Science News Ltd. (https://sci-news.co.

jp/). Unauthorized reproduction of the article and photographs is prohibited.