Gamma delta tocotrienols reduce hepatic triglyceride synthesis and VLDL secretion.
OBJECTIVE
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 triglyceride-rich 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.


CONCLUSIONS
Reduction in triglycerides synthesis and transport may be the primary benefit caused by ingesting γδT3 in human.
Zaiden
N
N
Davos Life Science Pte Ltd, Cardiovascular Research Laboratory Singapore, 16 Tuas South Street 5, Singapore.
Yap
W N
WN
Ong
S
S
Xu
C H
CH
Teo
V H
VH
Chang
C P
CP
Zhang
X W
XW
Nesaretnam
K
K
Shiba
S
S
Yap
Y L
YL
D000818:Animals; D053299:Apolipoprotein B-100 / Q000235:genetics / Q000378:metabolism; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D049109:Cell Proliferation; D002478:Cells, Cultured; D002839:Chromans / Q000494:pharmacology*; D051048:Diacylglycerol O-Acyltransferase / Q000235:genetics / Q000378:metabolism; D005260:Female; D006801:Humans; D006903:Hydroxymethylglutaryl CoA Reductases / Q000235:genetics / Q000378:metabolism; D008079:Lipoproteins, VLDL / Q000378:metabolism*; D008099:Liver / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D012333:RNA, Messenger / Q000235:genetics; D011973:Receptors, LDL / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051780:Sterol Regulatory Element Binding Protein 1 / Q000235:genetics / Q000378:metabolism; D051782:Sterol Regulatory Element Binding Protein 2 / Q000235:genetics / Q000378:metabolism; D014280:Triglycerides / Q000096:biosynthesis* / Q000378:metabolism; D014810:Vitamin E / Q000031:analogs & derivatives* / Q000494:pharmacology
D053299:Apolipoprotein B-100; D002839:Chromans; D008079:Lipoproteins, VLDL; D012333:RNA, Messenger; D011973:Receptors, LDL; D051780:Sterol Regulatory Element Binding Protein 1; D051782:Sterol Regulatory Element Binding Protein 2; D014280:Triglycerides; C030106:very low density lipoprotein triglyceride; D014810:Vitamin E; C082097:tocotrienol, delta; C013649:plastochromanol 8; C553220:HMGCR protein, human; D006903:Hydroxymethylglutaryl CoA Reductases; C494885:DGAT2 protein, human; D051048:Diacylglycerol O-Acyltransferase