NEDD4L knockdown reduced lipid accumulation in non-alcoholic fatty liver disease by promoting the activity of PI3K/AKT signaling pathway
Year: 2025
Type: article
Abstract: BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) represents a prevalent liver disease that influences the physical health of patients. Nonetheless, the exact pathogenesis of NAFLD remains unclear. OBJECT: To clarify how the neural precursor cell expressed developmentally downregulated 4-like (NEDD4L) regulates the lipid accumulation in the pathogenesis of NAFLD. METHODS: NAFLD mouse models received a high-fat diet (60% fat). NAFLD primary hepatocyte models were established by treating hepatocytes with oleate (OA). NEDD4L knockdown mice were purchased and fed a diet containing 60% fat. NEDD4L was silenced in primary hepatocytes by transfection. Liver tissues were stained via hematoxylin and eosin (HE). Primary hepatocytes and liver tissues were stained via Oil Red O. Triglyceride (TG) levels in liver tissues and primary hepatocytes were detected via enzyme-linked immunosorbent assay (ELISA). Protein expression was determined via Western blot (WB). RESULTS: NEDD4L expression was elevated in liver tissues of NAFLD mice (P < 0.01). In addition, NEDD4L knockdown led to a reduction in body weight, liver weight, lipid accumulation, and TG levels in the liver tissues of NAFLD mice (P < 0.01). In NAFLD primary hepatocytes, NEDD4L knockdown led to a reduction in lipid accumulation and TG levels (P < 0.01). In summary, NEDD4L knockdown promoted the PI3K/AKT signaling pathway activity and decreased inflammatory factor levels in both NAFLD mice and primary hepatocyte models (P < 0.01). CONCLUSION: NEDD4L knockdown increased the PI3K/AKT signaling pathway activity, leading to decreased lipid accumulation in NAFLD. Therefore, NEDD4L appears to be a useful target for NAFLD diagnosis and management.
Authors: Ju Zhou, Wu Li, Xiaowei Chi, Dingchun Li, Chunxia Yang, Zhiwen Duan
Language: English
Subfield: Epidemiology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,190
OpenAlex ID: W4417525012