Adiponectin, an adipose-derived
adipokine, possesses a hepatoprotective role in various liver disorders. It has been reported that
hypoadiponectinemia can affect with the progression of non-
alcoholic fatty liver diseases (
NAFLD).
Inflammasome activation has been recognized to play a major role during the progression of
NAFLD. This research aimed to explore the effect of
adiponectin on
palmitate (PA)-mediated NLRP3
inflammasome activation and its potential molecular mechanisms. Male
adiponectin-knockout (
adiponectin-KO) mice and C57BL/6 (wild-type) mice were fed a high-fat-diet (HFD) for 12 weeks as an in vivo model of non-
alcoholic steatohepatitis (NASH). Serum
biochemical markers, liver histology and
inflammasome-related gene and
protein expression were determined. In addition, the hepatocytes isolated from wide type mice were exposed to PA in the absence or presence of
adiponectin and/or AMPK inhibitor. The activation of NLRP3
inflammasome was assessed by
mRNA and
protein expression. Furthermore, ROS production and related signaling pathways were also evaluated. In the in vivo experiments, excessive hepatic steatosis with increased NLRP3
inflammasome and its complex expression were found in
adiponectin-KO mice compared to wild-type mice. Moreover, the expression levels of NLRP3
inflammasome pathway molecules (NFκB and ROS) were upregulated, while the phosphorylation levels of AMPK, JNK, and Erk1/2 were downregulated in
adiponectin-KO mice compared with wild-type mice. In the in vitro study, PA increased lipid droplet deposition,
NF-kB signaling and ROS production. Additionally, PA significantly promoted NLRP3
inflammasome activation and complex gene and
protein expression in hepatocytes.
Adiponectin could abolish PA-mediated
inflammasome activation and decrease ROS production, which was reversed by
AMPK inhibitor (compound C). Furthermore, the results showed that the inhibitory effect of
adiponectin on PA-mediated
inflammasome activation was regulated by AMPK-JNK/ErK1/2-NFκB/ROS signaling pathway.
Adiponectin inhibited PA-mediated NLRP3
inflammasome activation in hepatocytes.
Adiponectin analogs or AMPK agonists could serve as a potential novel agent for preventing or delaying the progression of NASH and
NAFLD.