Although elevated blood levels of trimethylamine N-oxide (TMAO) have been associated with atherosclerosis development in humans, the role of its gut microbiota-derived precursor, TMA, in this process has not been yet deciphered. Taking this into account, and the fact that increased intestinal fatty acid absorption contributes to atherosclerosis onset and progression, this study aimed to evaluate the effect of TMA on fatty acid absorption in a cell line that mimics human enterocytes. Caco-2 cells were treated with TMA 250 μM for 24 h. Fatty acid absorption was assessed by measuring the apical-to-basolateral transport and the intracellular levels of BODIPY-C12, a fluorescently labelled fatty acid analogue. Gene expression of the main intestinal fatty acid transporters was evaluated by real-time quantitative reverse transcription PCR. Compared to control conditions, TMA increased, in a time-dependent manner and by 20–50 %, the apical-to-basolateral transport and intracellular levels of BODIPY-C12 fatty acid in Caco-2 cells. Fatty acid transport protein 4 (FATP4) and fatty acid translocase (FAT)/CD36 gene expression were not stimulated by TMA, suggesting that TMA-induced increase in fatty acid transport may be mediated by an increase in FAT/CD36 and/or FATP4 activity and/or fatty acid passive transport. This study demonstrated that TMA increases the intestinal absorption of fatty acids. Future studies are necessary to confirm if this may constitute a novel mechanism that partially explains the existing positive association between the consumption of a diet rich in TMA sources (e.g. red meat) and the increased risk of atherosclerotic diseases.

Linoleic acid (LA) transport in rats with experimental short-term and long-term renal failure (RF) was compared with that of sham-operated normal animals on liberal food intake and pair-fed animals. The perfusions in vivo and incubations in vitro were conducted using a micellar solution containing a wide range of LA concentrations. Both absorption in vivo and uptake in vitro of LA were significantly reduced in animals with short-term RF. Lipid extraction and separation by thin-layer chromatography revealed a marked LA trapping as trilinolein (TL) in the perfused intestinal tissue in the short-term RF group. The esterification process, as defined by the rate of LA incorporation into TL, was moderately reduced in short-term RF animals. The thickness of the unstirred water layer showed no significant difference among the groups studied. In contrast, animals with long-term RF exhibited normal absorption of LA in vivo at all concentrations tested. In conclusion, LA absorption is reduced in short-term RF and restored in long-term RF. Several steps including LA transport into and TL transport out of the enterocyte and the esterification process were impaired in short-term RF. These changes are not due to alteration in the unstirred water layer, anorexia, weight loss or a rapid effect of uraemic chemical environment or circulatory factors.