CTRP3 protects against uric acid-induced endothelial injury by inhibiting inflammation and oxidase stress in rats.

Hyperuricemia, which contributes to vascular endothelial damage, plays a key role in multiple cardiovascular diseases. This study was designed to investigate whether C1q/tumor necrosis factor (TNF)-related protein 3 (CTRP3) has a protective effect on endothelial damage induced by uric acid and its underlying mechanisms. Animal models of hyperuricemia were established in Sprague-Dawley (SD) rats through the consumption of 10% fructose water for 12 weeks. Then, the rats were given a single injection of Ad-CTRP3 or Ad-GFP. The animal experiments were ended two weeks later. In vitro, human umbilical vein endothelial cells (HUVECs) were first infected with Ad-CTRP3 or Ad-GFP. Then, the cells were stimulated with 10 mg/dL uric acid for 48 h after pretreatment with or without a Toll-like receptor 4 (TLR4)-specific inhibitor. Hyperuricemic rats showed disorganized intimal structures, increased endothelial apoptosis rates, increased inflammatory responses and oxidative stress, which were accompanied by reduced CTRP3 and elevated TLR4 protein levels in the thoracic aorta. In contrast, CTRP3 overexpression decreased TLR4 protein levels and ameliorated inflammatory responses and oxidative stress, thereby improving the morphology and apoptosis of the aortic endothelium in rats with hyperuricemia. Similarly, CTRP3 overexpression decreased TLR4-mediated inflammation, reduced oxidative stress, and rescued endothelial damage induced by uric acid in HUVECs. In conclusion, CTRP3 ameliorates uric acid-induced inflammation and oxidative stress, which in turn protects against endothelial injury, possibly by inhibiting TLR4-mediated inflammation and downregulating oxidative stress.

CTRP3 ameliorates fructose-induced metabolic associated fatty liver disease via inhibition of xanthine oxidase-associated oxidative stress.

OBJECTIVES: The incidence of metabolic associated fatty liver disease (MAFLD) induced by high fructose consumption is dramatically increasing in the world while lacking specifically therapeutic drugs. The present study aimed to investigate the effect of complement C1q/tumor necrosis factor-related protein-3 (CTRP3) on fructose-induced MAFLD and its potential mechanisms. METHOD: The animal models with MAFLD were built with Sprague-Dawley (SD) rats drinking 10 % fructose solution for 12 weeks. Then, specific hepatic CTRP3 overexpression was conducted by a single caudal-vein injection of CTRP3-expressing adenoviruses. Rats were sacrificed two weeks later. RESULTS: Drinking 10 % fructose solution for 12 weeks successfully built the rats models with MAFLD. Fructose feeding markedly decreased hepatic CTRP3 expression in rats. However, CTRP3 overexpression in liver alleviated hyperuricemia, dyslipidemia, liver function injury, intrahepatic triglyceride (TG) accumulation and histological changes of hepatic steatosis in rats fed with fructose. CTRP3 overexpression also inhibited hepatic XO activity in liver and improved subsequent oxidative stress, accompanied with downregulation of gene expression of sterol-regulatory element binding protein 1c (SERBP-1c) and fatty acid synthase (FAS). CONCLUSION: CTRP3 attenuates MAFLD induced by fructose, which maybe partially attribute to rescued oxidative stress related with xanthine oxidase overactivity.