Elucidation of the mechanisms underlying n-3 polyunsaturated fatty acids mediated degradation of ChREBP

2015 Fiscal Year Final Research Report

• Project/Area Number: 26750041
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Eating habits
• Research Institution: Kobe University
• Principal Investigator: NAKAGAWA TSUTOMU 神戸大学, 医学(系)研究科(研究院), 講師 (50722063)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Keywords: ChREBP

Outline of Final Research Achievements

n-3 polyunsaturated fatty acids (PUFA) can reduce plasma triglyceride (TG) level. However, the underlying mechanism of plasma TG reduction remains unclear. Carbohydrate response element-binding protein (ChREBP) is a transcription factor responsible for the coordinated metabolism of carbohydrate and fat synthesis. It was reported that the inhibition of ChREBP in leptin-deficient mice improved plasma TG level. Therefore, it was suggested that ChREBP could be a protein affected by n-3 PUFA, which was involved in reducing plasma TG level. In this study, it was shown that n-3 PUFA could promote the degradation of ChREBP. Moreover, it was found that ChREBP was degraded via the autophagy-lysosomal pathway. The inhibitory effect on ChREBP activity by n-3 PUFA disappeared when the degradation of ChREBP was inhibited by chloroquine treatment. These results suggested that n-3 PUFA promoted the degradation of ChREBP by inducing autophagy, resulting in reduction of plasma TG level.

Free Research Field

生化学