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Water-soluble organosulfur compounds of garlic inhibit fatty acid and triglyceride syntheses in cultured rat hepatocytes

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Lipids

Abstract

The putative hypolipidemic effect of garlic remains controversial. To gain further insight into the effect of garlic on lipid metabolism, the present study determined the inhibitory effects of water-soluble organosulfur compounds present in garlic on triglyceride (TG) and fatty acid synthesis in cultured rat hepatocytes. When incubated at 0.05 to 4.0 mmol/L with cultured hepatocytes, S-allyl cysteine (SAC) and S-propyl cysteine (SPC) decreased [2-14C]acetate incorporation into triglyceride in a concentration-dependent fashion achieving a maximal inhibition at 4.0 mmol/L of 43 and 51%, respectively. The rate of [2-14C]acetate incorporation into phosphlipids was depressed to a similar extent by SAC and SPC. SPC, SAC, S-ethyl cysteine (SEC), and γ-glutamyl-S-methyl cysteine decreased [2-14C]acetate incorporation into fatty acid synthesis by 81, 59, 35, and 40%, respectively, at 2.0–4.0 mmol/L concentrations. Alliin, γ-glutamyl-S-allyl cysteine, γ-glutamyl-S-propyl cysteine S-allyl-N-acetyl cysteine, S-allylsulfonyl alanine, and S-methyl cysteine had no effect on fatty acid synthesis. The activities of lipogenic enzymes, fatty acid synthase (FAS), and glucose-6-phosphate dehydrogenase (G6PDH) were measured in cultured hepatocytes treated with the inhibitors. The activity of FAS in cells treated with 4.0 mmol/L SAC and SPC, respectively, was 32 and 27% lower than that of non-treated cells. Neither SAC nor SPC affected G6PDH activity. The results indicate that SAC, SEC, and SPC inhibit lipid biosynthesis in cultured rat hepatocytes, and further suggest that these S-alk(en)yl cysteines of garlic impair triglyceride synthesis in part due to decreased de novo fatty acid synthesis resulting from inhibition on FAS. Whether tissue concentrations of active garlic components can achieve levels required to inhibit TG synthesis in vivo warrants further investigation.

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Abbreviations

ANOVA:

analysis of variance

DMEM:

Dulbecco's modified Eagle medium

DTT:

dithiothreitol

FAS:

fatty acid synthase

FBS:

fetal bovine serum

G-6-P:

glucose-6-phosphate

G6PDH:

glucose-6-phosphate dehydrogenase

GSAC:

γ-glutamyl-S-allyl cysteine

GSMC:

γ-glutamyl-S-methyl cysteine

GSPC:

γ-glutamyl-S-propyl cysteine

IC50 :

concentration required for 50% maximal inhibition

LDL:

low density lipoprotein

PPB:

potassium phosphate buffer

SAC:

S-allyl cysteine

SAMC:

S-allyl mercaptocysteine

SANC:

S-allyl-N-acetyl cysteine

SASA:

S-allylsulfonyl alanine

SEC:

S-ethyl cysteine

SMC:

S-methyl cysteine

SPC:

S-propyl cysteine

TG:

triglyceride

VLDL:

very low density lipoprotein

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  1. Nutrition Department, The Pennsylvania State University, 129 South Henderson Building, 16802, University Park, PA

    Lijuan Liu & Yu-Yan Yeh

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  1. Lijuan Liu
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Liu, L., Yeh, YY. Water-soluble organosulfur compounds of garlic inhibit fatty acid and triglyceride syntheses in cultured rat hepatocytes. Lipids 36, 395–400 (2001). https://doi.org/10.1007/s11745-001-0734-4

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  • DOI: https://doi.org/10.1007/s11745-001-0734-4

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