The physiological and pathological contributions of environmental factors and ketone body utilization to obesity.

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K06639
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 47030:Pharmaceutical hygiene and biochemistry-related
• Research Institution: Hoshi University
• Principal Investigator: Yamasaki Masahiro 星薬科大学, 薬学部, 准教授 (80328921)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 臭化難燃剤 / アセトアセチルCoA合成酵素 / 脂肪細胞 / 褐色脂肪細胞

Outline of Final Research Achievements

Recent studies have suggested that exposure to brominated flame retardants (BFR) may play a pivotal role in the development of obesity and metabolic disorder in liver. Ketone bodies produced by β-oxidation are utilized by acetoacetyl-CoA synthetase (AACS), the novel cytosolic ketone body-utilizing enzyme. Previously, we reported that gene expression of AACS is upregulated in high-fat diet-induced obesity. Here, we examined the effects of BFR, tetrabromobisphenol A (TBBP-A), on gene expressions in adipocyte cell lines. Treatment with TBBP-A did not reveal any remarkable effects on lipid accumulation and mRNA expression of AACS and lipogenic factors in differentiated cells. In contrast, in undifferentiated cells, mRNA expression was upregulated for the lipid and ketone body utilizing factors and brown adipose tissue (BAT) related factors. These results suggest that TBBP-A may dysregulate lipid metabolism during ketone body utilization via AACS in undifferentiated adipocytes.

Free Research Field

分子生物学

Academic Significance and Societal Importance of the Research Achievements

本研究により、臭化難燃剤として広く使用されているTBBP-Aが、脂肪細胞の脂質-ケトン体に代謝に影響を与える環境由来物質である可能性が明らかとなった。また、その指標が従来は脂質代謝の余剰物質としてしか見られていなかったケトン体であること、申請者らのグループが独自に見出したケトン体利用酵素AACSがそれに深く関与することは、本研究の独自性を示すとともに、既存の研究グループでは明らかにし得なかったデータを多く含んでいることを示している。従って、今回明らかになったTBBP-Aの新たな作用の詳細な検討は、環境汚染が人間にもたらす新たなリスクを解明していくうえで、極めて大きな社会的意義があると考える。