Background: PNPLA3 is a gene regulated by nutritional status, which is closely related to non-alcoholic fatty liver disease. However, the mechanism of regulation for PNPLA3 remains to be fully clarified. The aim of this study was to investigate the acetylation level of H3K9 in the promoter region of PNPLA3 gene under different physiological and nutritional conditions, which might lay a foundation for understanding the epigenetic mechanism of PNPLA3 expression regulation. C57BL/6 mice were fed ad libitum (NC, N=10), fasted (N=10) for 24 hours, and re-fed (N=10) for 12 hours. Chromatin immunoprecipitation(CHIP)-qPCR were used in assaying the enrichment for histone active marks H3K9ac in liver PNPLA3. Real-time PCR was used to measure the mRNA expression of PNPLA3, and SIRT1 which is a known deacetylase affected by nutritional status.

Results: The results showed that the H3K9ac level in the PNPLA3 promoter was significantly decreased by fasting as compared with NC mice, while the inhibited H3K9ac level of fasting increased significantly after refeeding. The PNPLA3 mRNA level was markedly downregulated during fasting (0.90±0.16 vs. 2.03±0.55, P<0.05) and upregulated about 6-fold when fasted mice were refed (6.25±0.96 vs. 0.90±0.16, P<0.05). While contrary to PNPLA3, the mRNA expression of SIRT1 increased significantly during fasting (2.06±0.10 vs. 1.01±0.13, P<0.05) and decreased significantly after refeeding (0.99±0.04 vs. 2.06±0.10, P<0.05).

Conclusions: PNPLA3 gene expression is regulated by histone acetylation and SIRT1 may be involved in this regulatory mechanism.

Disclosure

X. Xu: None. H. Liang: None. Y. Chen: None.

© 2019 by the American Diabetes Association.
2019
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