Gamma delta tocotrienols reduce hepatic triglyceride synthesis and VLDL secretion

Area of Science:

• Biochemistry
• Nutritional Science
• Pharmacology

Background:

• Serum lipid levels, particularly triglycerides and cholesterol, are critical indicators of cardiovascular health.
• Tocotrienols, a form of vitamin E, have shown potential in modulating lipid metabolism.

Purpose of the Study:

• To investigate the lipid-lowering effects of gamma- and delta-tocotrienol (γδT3).
• To elucidate the mechanisms underlying γδT3's impact on lipid homeostasis.
• To evaluate the efficacy of γδT3 in preclinical and clinical settings.

Main Methods:

• In vitro studies using HepG2 liver cell line to assess gene expression and lipid synthesis.
• In vivo studies involving hypercholesterolemic mice to evaluate serum lipid profiles.
• A placebo-controlled human trial with borderline-high cholesterol patients.

Main Results:

• In vitro: γδT3 suppressed key lipid homeostasis genes (DGAT2, APOB100, SREBP1/2, HMGCR), reducing triglyceride, cholesterol, and VLDL synthesis, and enhanced LDL efflux via LDLr induction.
• In vivo (mice): γδT3 administration led to significant reductions in cholesterol (28%) and triglycerides (19%), with no change in HDL.
• Human trial: γδT3 (120 mg/day) significantly lowered serum triglycerides (28%) and reduced VLDL and chylomicrons, while total cholesterol, LDL, and HDL remained unchanged.

Conclusions:

• γδT3 demonstrates dual mechanisms for lipid reduction in vitro, impacting synthesis and efflux.
• In humans, γδT3's primary benefit appears to be the reduction of triglycerides and triglyceride-rich lipoproteins.
• Observed discrepancies between in vitro, in vivo, and human results may stem from differential γδT3 metabolism and LDL metabolism rates.