Resveratrol exerts a biphasic effect on apolipoprotein M.

Area of Science:

• Biochemistry and Molecular Biology
• Vascular Biology and Pathophysiology
• Nutraceuticals and Pharmacology

Background:

• Resveratrol is known for its diverse beneficial effects in pathophysiology, particularly in vascular biology.
• Apolipoprotein M (apoM) is a key carrier and modulator of sphingosine 1-phosphate (S1P), a critical vasoactive lipid mediator.

Purpose of the Study:

• To investigate the specific effects of resveratrol on apolipoprotein M (apoM) and sphingosine 1-phosphate (S1P) metabolism.
• To elucidate the molecular mechanisms underlying resveratrol's influence on apoM and S1P, including the role of sirtuin1.

Main Methods:

• Utilized HepG2 hepatoma cell line and human primary hepatocytes for in vitro studies.
• Employed C57BL/6 mice for in vivo experiments, administering resveratrol through chow.
• Quantified apoM, S1P, related enzymes, LDL receptors, and sirtuin1 activity using Western blotting, RT-PCR, and enzyme assays; utilized siRNA for gene knockdown.

Main Results:

• Resveratrol increased intracellular apoM and S1P in HepG2 cells; moderate concentrations elevated extracellular apoM, while high concentrations decreased it.
• Resveratrol activated sirtuin1 and increased LDL receptor expression in HepG2 cells; effects were consistent in human primary hepatocytes.
• In vivo, resveratrol-rich chow increased plasma and hepatic apoM and S1P levels in mice, without altering hepatic LDL receptor levels.

Conclusions:

• Resveratrol modulates both intracellular and extracellular levels of apoM and intracellular S1P.
• Findings suggest novel effects of resveratrol on the metabolic kinetics of S1P, a multifunctional bioactive phospholipid.
• Resveratrol's impact on apoM and S1P metabolism warrants further investigation for potential therapeutic applications in vascular health.