Naringenin attenuates non-alcoholic fatty liver disease by down-regulating the NLRP3/NF-κB pathway in mice.

Background And Purpose: Naringenin, a flavonoid compound with strong anti-inflammatory activity, attenuated non-alcoholic fatty liver disease (NAFLD) induced by a methionine-choline deficient (MCD) diet in mice. However, the mechanisms underlying this suppression of inflammation and NAFLD remain unknown.

Experimental Approach: WT and NLRP3 mice were fed with MCD diet for 7 days to induce NAFLD and were given naringenin by gavage at the same time. in vitro experiments used HepG2 cells, primary hepatocytes, and Kupffer cells (KCs) stimulated by LPS or LPS plus oleic acid (OA).

Key Results: Treating WT mice with naringenin (100 mg·kg ·day ) attenuated hepatic lipid accumulation and inflammation in the livers of mice given the MCD diet. NLRP3 mice showed less hepatic lipid accumulation than WT mice, but naringenin did not ameliorate hepatic lipid accumulation further in NLRP3 mice. Treating the HepG2 cells with naringenin or NLRP3 inhibitor MCC950 reduced lipid accumulation. Naringenin inhibited activation of the NLRP3/NF-κB pathway stimulated by OA together with LPS. In KCs isolated from WT mice, naringenin inhibited NLRP3 expression. Naringenin also inhibited lipid deposition, NLRP3 and IL-1β expression in WT hepatocytes but was not effective in NLRP3 hepatocytes. After re-expressing NLRP3 in NLRP3 hepatocytes by adenovirus, the anti-lipid deposition effect of naringenin was restored.

Conclusion And Implications: Naringenin prevented NAFLD via down-regulating the NLRP3/NF-κB signalling pathway both in KCs and in hepatocytes, thus attenuating inflammation in the mice livers.