Uptake and fate of ganglioside GD3 in human intestinal Caco-2 cells

Abstract

Ganglioside GD3 is a glycosphingolipid found in colostrum, developing tissues, and tumors and is known to regulate cell growth, differentiation, apoptosis, and inflammation. Feeding a GD3-enriched diet to rats increases GD3 in intestinal lipid rafts and blood. The mechanism, efficiency, and fate of ganglioside absorption by human enterocytes have not been investigated. A model to study GD3 uptake by human intestinal cells was developed to test the hypothesis that enterocyte GD3 uptake is time and concentration dependent, with uptake efficiency and fate influenced by route of delivery. Caco-2 cells were exposed to GD3 on the apical or basolateral membrane (BLM) side for 6, 24, and 48 h. GD3 uptake, retention, transfer, and metabolism was determined. GD3 uptake across the apical and BLM was time and concentration dependent and reached a plateau. GD3 uptake across the BLM was more efficient than apical delivery. Apical GD3 was metabolized with some cell retention and transfer, whereas basolateral GD3 was mostly metabolized. This study demonstrates efficient GD3 uptake by enterocytes and suggests that the route of delivery influences ganglioside uptake and fate.

Ganglioside Intake Increases Plasma Ganglioside Content in Human Participants

“…Uptake of ganglioside in vitro and in the intestine occurs by micelle absorption, monomer insertion, or receptor‐mediated uptake 49 . Metabolic kinetics of GD3 have been described in Caco‐2 cells 1 . Schnabl et al 1 have shown that GD3 is taken up by the intestinal brush‐border membrane and is mainly metabolized into new ganglioside species, with smaller portions being retained or transferred, whereas GD3 taken up by the basolateral membrane is not retained or transferred to any significant degree.…”

“…Safety and bioavailability of ganglioside have been demonstrated in several experimental models 1 . ‐ 4 Uptake of ganglioside has been shown in Caco‐2 intestinal epithelial, 1 breast, 2 and prostate cancer cells 3 in vitro and in rat brain, plasma, and intestine 4 in vivo. Safety of ganglioside for human consumption is presumed as ganglioside is a component of foods such as human breast milk, meat, and dairy 5 .…”

Dietary Ganglioside Reduces Proinflammatory Signaling in the Intestine

“…Several tissues have been shown to incorporate dietary gangliosides. Caco-2 cells incorporate GD3 [22] when provided with ganglioside in vitro [23]. Ganglioside uptake also occurs in several tissues in vivo .…”

“…Metabolic kinetics of GD3 has been described in depth in Caco-2 cells. GD3 taken up by the brush border membrane is mainly metabolized into new ganglioside species, with smaller portions being retained or transferred, whereas GD3 taken up by the basolateral membrane is not retained or transferred to any significant degree [22]. These observations suggest that each species of ganglioside localizes to particular regions of the enterocyte to carry out specific functions, which depend on site of uptake.…”

Influence of dietary gangliosides on neonatal brain development

“…29,[31][32][33][34][35][36][37][38][39][40][41] To gain an understanding of ganglioside metabolism, studies have injected gangliosides into animals and monitored ganglioside fate. Before cell uptake, gangliosides occur in aqueous solutions in the form of micelles, monomers, and oligomers.…”