Gamma delta tocotrienols reduce hepatic triglyceride synthesis and VLDL secretion

Aim: present study aimed to elucidate the suppression of serum lipids by gamma- and delta-tocotrienol (γδt3). methods: the lipid-lowering effects of γδt3 were investigated using hepg2 liver cell line,hypercholesterolemic mice and borderline-high cholesterol patients. results: in-vitro results demonstrated two modes of action. first,γδt3 suppressed the upstream regulators of lipid homeostasis genes (dgat2,apob100,srebp1/2 and hmgcr) leading to the suppression of triglycerides,cholesterol and vldl biosyntheses. second,γδt3 enhanced ldl efflux through induction of ldl receptor (ldlr) expression. treatment of ldlr-deficient mice with 1 mg/day (50 mg/kg/day) γδt3 for one-month showed 28%,19% reduction in cholesterol and triglyceride levels respectively,whereas hdl level was unaltered. the lipid-lowering effects were not affected by alpha-tocopherol (αtp). in a placebo-controlled human trial using 120 mg/day γδt3,only serum triglycerides were lowered by 28% followed by concomitant reduction in the triglyceriderich vldl and chylomicrons. in contrast,total cholesterol,ldl and hdl remained unchanged in treated and placebo groups. the discrepancies between in-vitro,in-vivo and human studies may be attributed to the differential rates of post-absorptive γδt3 degradation and ldl metabolism. conclusion: reduction in triglycerides synthesis and transport may be the primary benefit caused by ingesting γδt3 in human.