Epigallocatechin gallate increases the formation of cytosolic lipid droplets and decreases the secretion of apoB-100 VLDL

Abstract

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.-Li, L., P. Stillemark-Billton, C. Accumulation of triglycerides, particularly in the liver and skeletal muscle, is associated with metabolic disorders such as insulin resistance and type 2 diabetes (1, 2), diseases that are strong risk factors for cardiovascular diseases. Accumulation of triglycerides in the liver is also the landmark of nonalcoholic fatty liver disease, which results in inflammation and liver damage (3). Moreover, the stores of triglyceride in the liver fuel the assembly and secretion of VLDLs (3-6). Thus, it is obvious that elucidation of the mechanism of the storage of lipid in the cytosol is important for our understanding of the pathogenesis of major metabolic diseases.Triglycerides are stored in the cytosol in the form of lipid droplets (also referred to as lipid bodies) (for reviews, see 7, 8). These droplets are formed from microsomes (9; see also 7, 8 for reviews) as a primordial droplet with a diameter of z0.1 Am It has been demonstrated that the fatty acids used for the biosynthesis of VLDL triglycerides are derived from triglycerides stored in the liver (3). The triglycerides are hydrolyzed and reesterified into new triglycerides before being assembled into VLDL (4-6). VLDLs are assembled in a complex series of events (for reviews, see 11-16), starting with the formation of a primordial particle (pre-VLDL) during the translation and translocation of apolipoprotein B-100 (apoB-100) to the lumen of the endoplasmic reticulum. This step is catalyzed by the microsomal triglyceride transfer protein (MTP). The pre-VLDL par-

Oxysterol Binding Protein Induces Upregulation of SREBP-1c and Enhances Hepatic Lipogenesis

“…24 The relationship of hepatic TG accumulation and VLDL secretion is complex. 11,25 Overexpression of the nuclear forms of SREBP-1 represents an extreme situation leading to gross alterations of hepatic lipid metabolism not comparable to the present study, in which the observed effects on lipogenesis and SREBP-1c expression/maturation were relatively mild.…”

“…24 The relationship of hepatic TG accumulation and VLDL secretion is complex. 11,25 Overexpression of the nuclear forms of SREBP-1 represents an extreme situation leading to gross alterations of hepatic lipid metabolism not comparable to the present study, in which the observed effects on lipogenesis and SREBP-1c expression/maturation were relatively mild.Insulin induces lipogenesis via phosphoinositide-3-kinase (PI-3-K) and Akt-dependent signaling cascades that upregulate SREBP-1c transcription. 26 -28 Moreover, insulin enhances the proteolytic activation of SREBP-1c and increases the half-life of nSREBP-1c.…”

Anti‐infective properties of epigallocatechin‐3‐gallate (EGCG), a component of green tea

“…When they performed the first infection experiments with EGCG, a potent inhibition of HCV infection was noted, and the green tea molecule was identified as a novel HCV entry inhibitor (Ciesek et al, 2011). Calland and co-workers became interested in testing EGCG because it was reported to increase lipid droplet formation and to impair lipoprotein secretion in hepatocytes, two cellular functions known to play a role in the life cycle of HCV (Li et al, 2006). In these three studies it was clearly demonstrated that entry of cell culture-derived particles (HCVcc) as well as HCV pseudoparticles (HCVpp) are inhibited by EGCG independent of the HCV genotype (Ciesek et al, 2011;Calland et al, 2012;Chen et al, 2012).…”

Growth arrest and apoptosis induced by quercetin is not linked to adipogenic conversion of human preadipocytes

“…Epigallocatechin gallate (EGCG) inhibits growth of 3T3-L1 preadipocytes [21] or lipogenesis of 3T3-L1 adipocytes [22][23][24], whereas it increases the amount of cytosolic lipid droplets in NIH 3T3 and McA-RH7777 cells [25]. It has been reported that quercetin markedly inhibits lipogenesis in association with apoptosis in cancer cells [20], but it is uncertain whether quercetin affects the lipogenesis of adipocytes.…”