PMID:
Br J Pharmacol. 2019 Nov 23. Epub 2019 Nov 23. PMID: 31758699
Abstract Title:
Naringenin attenuates nonalocholic fatty liver disease by downregulating NLRP3/NF-κB pathway in mice.
Abstract:
BACKGROUND AND PURPOSE: Our previous study demonstrate that Naringenin (NGN), a flavonoid compound with strong anti-inflammatory activity, could attenuate nonalcoholic fatty liver disease (NAFLD) induced by a methionine-choline deficient (MCD) diet in mice. However, its underlying mechanisms in regulation of inflammation and NAFLD remain unknown.EXPERIMENTAL APPROACH: WT and NLRP3-/- mice were fed with MCD diet for seven days to induce NAFLD, and administrated by gavage with different doses of NGN at the same time. In vitro experiments were implemented on HepG2 cells, primary hepatocytes and Kupffer cells (KCs) stimulated by lipopolysaccharide (LPS) or LPS plus oleic acid (OA).KEY RESULTS: Treating the WT mice with NGN (100 mg/kg/d) significantly attenuated hepatic lipid accumulation and inflammation activation in the mice livers induced by MCD diet. NLRP3-/- mice showed less hepatic lipid accumulation than WT mice, but NGN treatment could not ameliorate hepatic lipid accumulation further in NLRP3-/- mice. Treating the HepG2 cells with NGN or NLRP3 inhibitor MCC950 reduced lipid accumulation, and NGN inhibited activation of NLRP3/NF-κB pathway stimulated by OA together with LPS. In KCs isolated from WT mice, NGN could inhibit NLRP3 expression. Besides, NGN also inhibited lipid deposition, NLRP3 and IL-1β expression in WT hepatocytes, but lost efficacy in NLRP3-/- hepatocytes. After re-expressing NLRP3 in NLRP3-/- hepatocytesby adenovirus, the anti-lipid deposition effect of NGN was restored.CONCLUSION AND IMPLICATIONS: Our results elucidated that NGN prevented NAFLD via downregulating NLRP3/NF-κB signaling pathway both in KCs and hepatocytes, thus attenuating inflammation in the mice livers.
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