Journal
BIOCHEMICAL PHARMACOLOGY
Volume 136, Issue -, Pages 136-149Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bcp.2017.04.014
Keywords
Apigenin; NAFLD; Nrf2; PPAR gamma
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Funding
- open fund of State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, China [KFGN-201501]
- National Natural Science Foundation of China [81503082, 81673439, 81473220]
- Natural Science Foundation of Jiangsu Province of China [BK20150575]
- Postdoctoral Science Foundation of China [2015M570437]
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Lipid metabolic disorders and oxidative stress in the liver are key steps in the progression of nonalcoholic fatty liver disease (NAFLD), which is a major risk factor for the development of metabolic syndrome. To date, no pharmacological treatment for this condition has been approved. Our previous study has found that the food-derived compound apigenin (Api) significantly attenuates obesity induced metabolic syndrome by acting as a peroxisome proliferator-activated receptor gamma modulator (PPARM). Herein, a high fat diet (HFD) induced NAFLD model was used to dig out whether Api had the effect on NAFLD. The results showed that Api had obvious effect in restraining NAFLD progression, including attenuating HFD induced lipid accumulation and oxidative stress in vivo. As a PPARM, although Api did significantly inhibit the expression of PPAR gamma target genes encoding the protein associated with lipid metabolism, it had no obvious activating effect on PPAR gamma. Interestingly, we found that Api promoted Nrf2 into the nucleus, thereby markedly activating Nrf2 to inhibit the lipid metabolism related genes and increase the oxidative stress related genes. Further Nrf2 knockdown/knockout and overexpression experiments showed that Api regulating PPAR gamma target genes was dependent on Nrf2 activation and the activation of Nrf2 counteracted the activation effect of PPAR gamma by Api. Importantly, we also found that Api might bind with Nrf2 via auto dock and ITC assay. Therefore, our results indicate that Api ameliorates NAFLD by a novel regulating mode of Nrf2 and PPAR gamma in inhibiting lipid metabolism and oxidative stress abnormity. (C) 2017 Elsevier Inc. All rights reserved.
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