Abstract
Nonalcoholic fatty liver disease (NAFLD) is a kind of liver lipid synthesis and degradation imbalance related with metabolic syndrome. Celecoxib shows the function of ameliorating NAFLD, but the underlying mechanisms remain unknown. Here, we discuss the possible mechanisms of celecoxib alleviating NAFLD by restoring autophagic flux. Lipids were accumulated in L02 cells treated with palmitate as well as SD rats fed with high-fat diet. Western blot showed that LC3 II/I was higher and p62 was lower on the early stage of steatosis while on the late stage both of them were higher, indicating that autophagic flux was activated on the early stage of steatosis, but blocked on the late stage. Rapamycin alleviated steatosis with activating autophagic flux while chloroquine aggravated steatosis with inhibiting autophagic flux. COX-2 siRNA and celecoxib were used to inhibit COX-2. Western blot and RFP-GFP-LC3 double fluorescence system indicated that celecoxib could ameliorate steatosis and restore autophagic flux in L02 cells treated with palmitate as well as SD rats fed with high-fat diet. In conclusion, celecoxib partially restores autophagic flux via downregulation of COX-2 and alleviates steatosis in vitro and in vivo.
Highlights
Due to the modern sedentary and food-abundant lifestyle, nonalcoholic fatty liver disease (NAFLD) has become one of the most common liver diseases around world[1]
While at 24 h and 36 h, both of LC3 II/I and p62 were increased, which indicated that autophagic flux was activated on the early stage of steatosis but blocked at the late hour
Nonalcoholic fatty liver disease (NAFLD) is a complex multifactorial chronic disease which is charactered by an excessively high accumulation of fat deposits in the liver resulting from causes other than chronic alcohol abuse and drugs[23]
Summary
Due to the modern sedentary and food-abundant lifestyle, nonalcoholic fatty liver disease (NAFLD) has become one of the most common liver diseases around world[1]. NAFLD can progress to liver cancer without fibrosis. Recent studies suggest that celecoxib plays an important role in the treatment of NAFLD5. COX-2 activity has influence on insulin sensitivity[10], and acts as pro-inflammatory mediator during the progression of NAFLD11. It has gained increasing attention on the mechanisms by which celecoxib protects against the development of NAFLD. Many studies suggested that celecoxib could attenuate liver steatosis and inflammation in NAFLD5. Celecoxib may alleviate liver inflammation through regulation of NF-kB pathway as well as steatosis via suppression of non-canonical Wnt signaling pathway[14]. Recent studies suggested that impaired autophagic flux is associated with the progress of NAFLD20,21. We try to figure out whether celecoxib attenuates hepatic steatosis by regulating autophagic flux both in vivo and in vitro
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