Metabolism and Health Effects of Rare Sugars in a CACO-2/HepG2 Coculture Model

Abstract

Non-alcoholic fatty liver disease (NAFLD) has become the most prevalent liver disease worldwide and is impacted by an unhealthy diet with excessive calories, although the role of sugars in NAFLD etiology remains largely unexplored. Rare sugars are natural sugars with alternative monomers and glycosidic bonds, which have attracted attention as sugar replacers due to developments in enzyme engineering and hence an increased availability. We studied the impact of (rare) sugars on energy production, liver cell physiology and gene expression in human intestinal colorectal adenocarcinoma (Caco-2) cells, hepatoma G2 (HepG2) liver cells and a coculture model with these cells. Fat accumulation was investigated in the presence of an oleic/palmitic acid mixture. Glucose, fructose and galactose, but not mannose, l-arabinose, xylose and ribose enhanced hepatic fat accumulation in a HepG2 monoculture. In the coculture model, there was a non-significant trend (p = 0.08) towards higher (20–55% increased) median fat accumulation with maltose, kojibiose and nigerose. In this coculture model, cellular energy production was increased by glucose, maltose, kojibiose and nigerose, but not by trehalose. Furthermore, glucose, fructose and l-arabinose affected gene expression in a sugar-specific way in coculture HepG2 cells. These findings indicate that sugars provide structure-specific effects on cellular energy production, hepatic fat accumulation and gene expression, suggesting a health potential for trehalose and l-arabinose, as well as a differential impact of sugars beyond the distinction of conventional and rare sugars.

Intestinal Barrier Dysfunction and Gut Microbiota in Non-Alcoholic Fatty Liver Disease: Assessment, Mechanisms, and Therapeutic Considerations

“…The Caco-2/target-cell co-culture model is primarily used to explore the immune response of intestinal cells and its relation to the function of the intestinal barrier. Through the use of a Caco-2/HepG2 cell co-culture model, researchers found that alginate was less likely to induce intracellular fat accumulation compared to glucose, maltose, trehalose and inulin, suggesting that alginate may be more beneficial to individuals with NAFLD [99]. Camille et al identified that the Caco-2/TC7 cell line, derived from human cells, serves as an effective in vitro model for studying the molecular mechanisms of TICE enterocytes.…”

Tactics with Prebiotics for the Treatment of Metabolic Dysfunction-Associated Fatty Liver Disease via the Improvement of Mitophagy

“…Trehalose is a natural saccharide that could alter autophagy [ 88 ], initiating lysosomal temporary damage [ 89 ]. A health benefit for trehalose has been proposed in HepG2 cells [ 90 ]. The action mechanisms of trehalose may involve the inhibition of glucose transporters leading to AMPK-activation, which could affect the autophagy [ 91 ].…”

Preparation of Controlled Multicompartmental Gel Microcarriers Based on Aqueous Two-Phase Emulsions for 3D Partitioned Cell Coculture In Vitro

“…Hence, in order to investigate the indirect interactions among multiple cells in different tissues or organs under physiological or pathological conditions, it was necessary to coculture multiple cells in vitro to replicate the natural in vivo environment . In the traditional two-dimensional (2D) coculture systems like transwell, cells exhibit significant differences in morphology compared with those growing in the natural three-dimensional (3D) environment in vivo. − Additionally, the physiological or metabolic traits of cells cultivated on a 2D surface are entirely distinct from those present in vivo, thereby hindering the discovery of potential cellular interaction mechanisms. Hence, several methods have been developed in recent years to create compartmentalized carriers with intricate geometries capable of selectively encapsulating multiple cell types simultaneously for an in vitro 3D coculture.…”