Netrin-1 attenuates hepatic steatosis via UNC5b/PPARγ-mediated suppression of inflammation and ER stress.

Choi S. W., Oh H., Park S. Y., Cho W., HASSIBELNABY A. M. A., Baygutalp N., ...Daha Fazla

Life sciences, cilt.311, sa.Pt B, ss.121149, 2022 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 311 Sayı: Pt B
  • Basım Tarihi: 2022
  • Doi Numarası: 10.1016/j.lfs.2022.121149
  • Dergi Adı: Life sciences
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, BIOSIS, CAB Abstracts, Chimica, EMBASE, MEDLINE, Veterinary Science Database
  • Sayfa Sayıları: ss.121149
  • Anahtar Kelimeler: Netrin-1, ER stress, Metabolic-associated fatty liver disease, PPAR?, Inflammation, Autophagy, ENDOPLASMIC-RETICULUM STRESS, ACTIVATED RECEPTOR-GAMMA, UNC5B RECEPTOR, PPAR-GAMMA, INJURY, AUTOPHAGY, ISCHEMIA, PATHWAY, OBESITY, BRAIN
  • Atatürk Üniversitesi Adresli: Evet

Özet

© 2022 Elsevier Inc.Aims: The current study investigated whether netrin-1 can attenuate hepatic steatosis through PPARγ/autophagy-mediated suppression of inflammation and endoplasmic reticulum (ER) stress in experimental animal models. Main methods: Hepatic steatosis was induced by a high-fat diet in experimental mice. Recombinant mouse netrin-1 was administered via the tail vein (1 μg/mouse, once every two days). Serum inflammatory cytokines and hepatic inflammatory and ER stress markers were determined in mice using ELISA and western blotting protocol. Key findings: We found that netrin-1 expression was significantly increased (P < 0.05) in cultured macrophages treated with supernatants of subcutaneous adipocytes in the presence of palmitate and subcutaneous fat of obese mice. Recombinant netrin-1 treatment promoted PPARγ expression and autophagy, thereby attenuating inflammation and ER stress, lipid accumulation, and the expression of lipogenic proteins in mouse primary hepatocytes. High-fat diet (HFD) treatment increased hepatic inflammation and ER stress, causing hepatic steatosis in experimental mice. However, administration of netrin-1 reversed the effects of HFD on hepatic ER stress and lipid deposition. Significance: These results suggest that subcutaneous adipose macrophage-derived netrin-1 ameliorates inflammation and ER stress in the liver, which in turn alleviates hepatic steatosis by enhancing basal PPARγ/autophagy-dependent signaling. The current study sheds light on the pathogenesis of hepatic steatosis in obesity and provides a promising therapeutic approach for treating metabolic-associated fatty liver disease (MAFLD).