Netrin-1 attenuates hepatic steatosis via UNC5b/PPARγ-mediated suppression of inflammation and ER stress.
Life sciences, cilt.311, sa.Pt B, ss.121149, 2022 (SCI-Expanded, Scopus)
- 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).