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Journal of Lipid Research, Vol. 47, 67-77, January 2006 Epigallocatechin gallate increases the formation of cytosolic lipid droplets and decreases the secretion of apoB-100 VLDL
Wallenberg Laboratory for Cardiovascular Research, Göteborg University, Sahlgrenska University Hospital, SE-413 45 Göteborg, Sweden Published, JLR Papers in Press, October 14, 2005. 1 L. Li, P. Stillemark-Billton, C. Beck, and P. Boström contributed equally to this work.
2 To whom correspondence should be addressed. e-mail: sven-olof.olofsson{at}wlab.gu.se Epigallocatechin gallate (EGCG) increases the formation of cytosolic lipid droplets by a mechanism that is independent of the rate of triglyceride biosynthesis and involves an enhanced fusion between lipid droplets, a process that is crucial for their growth in size. EGCG treatment reduced the secretion of both triglycerides and apolipoprotein B-100 (apoB-100) VLDLs but not of transferrin, albumin, or total proteins, indicating that EGCG diverts triglycerides from VLDL assembly to storage in the cytosol. This is further supported by the observed increase in both intracellular degradation of apoB-100 and ubiquitination of the protein (indicative of increased proteasomal degradation) in EGCG-treated cells. EGCG did not interfere with the microsomal triglyceride transfer protein, and the effect of EGCG on the secretion of VLDLs was found to be independent of the LDL receptor. Thus, our results indicate that EGCG promotes the accumulation of triglycerides in cytosolic lipid droplets, thereby diverting lipids from the assembly of VLDL to storage in the cytosol. Our results also indicate that the accumulation of lipids in the cytosol is not always associated with increased secretion of VLDL.
Supplementary key words intracellular degradation ubiquitination low density lipoprotein receptor apolipoprotein B-100 Abbreviations: apoB-100, apolipoprotein B-100; EGCG, epigallocatechin gallate; GFP, green fluorescent protein; HAT, histidine affinity tag; LDLR, low density lipoprotein receptor; MTP, microsomal triglyceride transfer protein; PA, phosphatidic acid; PLD, phospholipase D
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