| First Author | Hao YR | Year | 2018 |
| Journal | Biochem Biophys Res Commun | Volume | 503 |
| Issue | 2 | Pages | 564-571 |
| PubMed ID | 29852170 | Mgi Jnum | J:273417 |
| Mgi Id | MGI:6276772 | Doi | 10.1016/j.bbrc.2018.05.187 |
| Citation | Hao YR, et al. (2018) Suppression of NF-kappaB activation by PDLIM2 restrains hepatic lipogenesis and inflammation in high fat diet induced mice. Biochem Biophys Res Commun 503(2):564-571 |
| abstractText | Non-alcoholic fatty liver disease (NAFLD) is characterized by hepatic steatosis, insulin resistance, dyslipidemia and a systemic pro-inflammatory response, a leading cause of cirrhosis and hepatocellular carcinoma. Here, we showed that PDZ-LIM domain-containing protein 2 (PDLIM2) was an effective suppressor of steatohepatitis. After 16 weeks on a high fat diet (HFD), obesity, insulin resistance, hepatic dyslipidemia and inflammation were markedly aggravated in PDLIM2-knockout (KO) mice. PDLIM2 deletion resulted in lipid accumulation in liver tissue samples of HFD-induced mice, as evidenced by the significant increase of hepatic TG and TC through reducing the expression of lipogenesis- and transcriptional regulators of lipid metabolism-related genes and enhancing fatty acid oxidation-associated molecules. In addition, PDLIM2-ablation promoted the expression of pro-inflammatory cytokines by activating nuclear factor kappa-B (NF-kappaB) signaling pathway, as supported by the remarkable increase of phosphorylated IKKbeta, IkappaBalpha and NF-kappaB expressions in liver of HFD-fed mice. Of note, the in vitro study demonstrated that PDLIM2 ablation-enhanced inflammatory response and disorder of lipid metabolism were abrogated by suppressing NF-kappaB activity. Collectively, the findings could lead to the development of potential therapeutic strategy to prevent NAFLD and associated metabolic disorders by targeting PDLIM2. |
