Effects of fibronectin/integrin β signaling on short-term high fat diet induced hepatic steatosis and the underlying mechanism

Objective To investigate the effects of fibronectin/ integrin β signaling on short-term high fat diet induced hepatic steatosis and the underlying mechanism. Methods Male C57BL/6 mice were treated with high fat diet or high fat diet combined with ATN161, an inhibitor of integrin β. Serum biochemical parameters and liver histological examinations were observed. The expression of lipid metabolic genes in mice liver were detected with realtime PCR and the protein levels of peroxisome proliferator-activated receptor γ(PPAR γ)and stearic acyl coenzyme A desaturase 1(SCD1)were determined with Western blot. Results (1)High fat diet increased hepatic lipid accumulation and the expressions of fibronectin and α-smooth muscle actin(α-SMA). (2)ATN161 down-regulated the expression of α-SMA while increased hepatic lipid accumulation and the expression of genes involved in lipogenesis and lipid uptake in high fat diet fed mice. The up-regulated genes were target genes of PPAR γ, which was also up-regulated. The protein levels of PPAR γ and SCD1 were also increased. (3)The inhibiting effects of fibronectin on lipogenesis were significantly attenuated by ATN161 in HepG2 cells. Conclusion Inhibition of fibronectin/integrin β signaling with ATN161 may block hepatic fibrotic signaling at the expense of increasing hepatic lipid accumulation through PPAR γ in mice fed with high fat diet during a short term. (Chin J Endocrinol Metab, 2016, 32: 773-780) Key words: Fibronectin; Integrin β; High fat diet; Nonalcoholic fatty liver disease; Peroxisome proliferator-activated receptor γ