Jerusalem artichoke extracts regulate the gene expression of key enzymes involved in fatty acid biosynthesis

Abstract

Jerusalem artichoke (JA) is a traditional remedy for alleviating symptoms of diabetes. In fact, the suppressive effects of JA on blood sugar have been reported in multiple studies since 1934. Recent studies have indicated that type II diabetes is often caused by insulin resistance rather than insulin reduction and that increased blood and interstitial fatty acid levels contribute to insulin resistance and the development of diabetes. However, whether JA affects human lipogenesis has not been studied. Here, we elucidated the effects of JA on the expression of two key enzymes involved in fatty acid biosynthesis, fatty acid synthase (FASN) and acetyl-CoA carboxylase (ACACA), using three human neuroblastoma and colon and liver cancer cell lines. Caffeine and ICRF193, a catalytic inhibitor of topoisomerase II (TOP2), were included as positive controls, and JA was extracted into water- or dimethyl sulfoxide-soluble components, termed H-JA and D-JA. Metabolomics analyses using gas chromatography-time of flight/mass spectrometry and in-silico analyses showed differentially enriched chemical compounds in H-JA and D-JA, suggesting their distinctive bioactivities including fatty acid metabolism. D-JA significantly reduced the expression of FASN and ACACA at the mRNA and protein levels. D-JA-treated cells exhibited altered TOP2 levels and FASN/ACACA expression appeared to be controlled by TOP2 activity and levels. Taken together, our study revealed a novel effect of JA extracts on inhibiting the expression of the key enzymes involved in the fatty acid biosynthesis and suggested the potential of JA as a natural medicinal agent to control lipogenesis in humans.