Suppression of NF-κB activation by PDLIM2 restrains hepatic lipogenesis and inflammation in high fat diet induced mice

Journal Article · Sat Sep 15 04:00:00 EDT 2018 · Biochemical and Biophysical Research Communications

DOI:https://doi.org/10.1016/J.BBRC.2018.05.187· OSTI ID:23105608

Hao, Ya-Rong; Tang, Feng-Juan; Zhang, Xue ^[1]; Wang, Hui ^[2]

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1. Department of Geriatrics, Renmin Hospital of Wuhan University, Wuhan, 430060 (China)
2. Department of Pharmacy, Renmin Hospital of Wuhan University, Wuhan, 430060 (China)

Highlights: • PDLIM2 deficiency promotes HFD-induced mice obesity and insulin resistance. • PDLIM2 deficiency promotes hepatic dyslipidemia in HFD-induced mice. • PDLIM2 deficiency intensifies HFD-induced hepatic inflammation. • Reducing NF-κB activation attenuates PDLIM2 deficiency-exacerbated inflammation and dyslipidemia in PAL-treated primary hepatocytes. 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-κB) signaling pathway, as supported by the remarkable increase of phosphorylated IKKβ, IκBα and NF-κB 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-κB activity. Collectively, the findings could lead to the development of potential therapeutic strategy to prevent NAFLD and associated metabolic disorders by targeting PDLIM2.

• OSTI ID: 23105608
• Journal Information: Biochemical and Biophysical Research Communications, Journal Name: Biochemical and Biophysical Research Communications Journal Issue: 2 Vol. 503; ISSN 0006-291X; ISSN BBRCA9
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
HEPATOMAS
INFLAMMATION
INSULIN
LIVER
LIVER CELLS
LYMPHOKINES
METABOLIC DISEASES
MICE