Atorvastatin remodels lipid distribution between liver and adipose tissues through blocking lipoprotein efflux in fish
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Date
2023-03-01
Journal Title
Journal ISSN
Volume Title
Publisher
American Physiological Society
Abstract
The regulation of cholesterol metabolism in fish is still unclear. Statins play important roles in promoting cholesterol metabolism development in mammals. However, studies on the role of statins in cholesterol metabolism in fish are currently limited. The present study evaluated the effects of statins on cholesterol metabolism in fish. Nile tilapia (Oreochromis niloticus) were fed on control diets supplemented with three atorvastatin levels (0, 12, and 24 mg/kg diet, ATV0, ATV12, and ATV24, respectively) for 4 wk. Intriguingly, the results showed that both atorvastatin treatments increased hepatic cholesterol and triglyceride contents mainly through inhibiting bile acid synthesis and efflux, and compensatorily enhancing cholesterol synthesis in fish liver (P < 0.05). Moreover, atorvastatin treatment significantly inhibited hepatic very-low-density lipoprotein (VLDL) assembly and thus decreased serum VLDL content (P < 0.05). However, fish treated with atorvastatin significantly reduced cholesterol and triglycerides contents in adipose tissue (P < 0.05). Further molecular analysis showed that atorvastatin treatment promoted cholesterol synthesis and lipogenesis pathways, but inhibited lipid catabolism and low-density lipoprotein (LDL) uptake in the adipose tissue of fish (P < 0.05). In general, atorvastatin induced the remodeling of lipid distribution between liver and adipose tissues through blocking VLDL efflux from the liver to adipose tissue of fish. Our results provide a novel regulatory pattern of cholesterol metabolism response caused by atorvastatin in fish, which is distinct from mammals: cholesterol inhibition by atorvastatin activates hepatic cholesterol synthesis and inhibits its efflux to maintain cholesterol homeostasis, consequently reduces cholesterol storage in fish adipose tissue.
Description
Keywords
atorvastatin, cholesterol metabolism, lipid metabolism, Nile tilapia
Citation
Rui-Xin Li, Ling-Yun Chen, Samwel M. Limbu, Bing Yao, Yi-Fan Qian, Wen-Hao Zhou, Li-Qiao Chen, Fang Qiao, Mei-Ling Zhang, Zhen-Yu Du and Yuan Luo (2023). Atorvastatin remodels lipid distribution between liver and adipose tissues through blocking lipoprotein efflux in fish. American Journal of Physiology-Regulatory, Integrative and Comparative Physiology, 324(3): R281-R292. https://doi.org/10.1152/ajpregu.00222.2022