48 / 2021-07-30 11:40:09

Piperine Improves Lipid Metabolic Profile by Upregulating of SR-B1 and ABCG8 Transporters in High-fat Diet-fed Mice

piperine,ABCG8,SR-B1,lipid

Scope:

Atherosclerotic cardiovascular disease is the leading cause of mortality worldwide, which is characterized by narrowed and hardened arteries due to the deposition of fatty plaques. Cholesterol-lowing therapy effectively inhibits development of atherosclerosis. Piperine from black pepper is reported to function as hypocholesterolemic agent, but how it lowers the blood cholesterol remains unclear. In this study, we investigated the hypolipidemic effect of piperine and explored its effect on the expression of crucial cholesterol transporters in livers and small intestines in high-fat diet (HFD)-fed mice. In addition, the hypolipidemic effect of piperine derivative (PD) was also evaluated in vivo.

Methods and results:

Intragastric administrations of piperine (25 mg/kg/day) for 8 weeks significantly reduced the plasma triglyceride (TG), total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) in high-fat diet (HFD)-fed mice. H&E staining indicated that piperine significantly decreased hepatic lipid accumulation compared with the control group. The Oil Red O staining further showed that piperine attenuated lipid deposition in liver HepG2 cells in concentration-dependent manner. Mechanistically, piperine treatment caused a significant upregulation of hepatic scavenger receptor B1 (SR-B1) in the liver and transporter protein of ATP binding cassette SGM8 (ABCG8) in the small intestine.

Intragastric administrations of PD (3, 10 mg/kg) also showed hypolipidemic activity and decreased levels of serum TG, TC and LDL-C, which was similar to atorvastatin. Besides, PD significantly attenuated the lipid deposition in livers of HFD mice.

Conclusions:

1. Both piperine and PD possesses hypolipidemic activity, and the latter is stronger.

2. Piperine improves lipid metabolic profile that is involved in the reverse cholesterol transport (RCT)-mediated mechanism through upregulation of SR-B1 in the liver and ABCG8 in the small intestine.