Synthesis and metabolism of glycerol-3H triether, a nonabsorbable oil-phase marker for lipid absorption studies

A saturated mixed-chain glycerol triether, 1-hexadecyl-2,3-didodecyl glycerol (1-hexadecoxy-2,3-didodecoxypropane), was synthesized with (3)H at positions 9 and 10 or (14)C at position 1 of the hexadecyl moiety. In acute feeding experiments in rats, less than 0.2% of the triether was absorbed, based on lymph and fecal recoveries. Radioactivity was present exclusively as triether in feces, indicating that it was not degraded by digestive or bacterial enzymes. Chronic feeding experiments in rats confirmed the nonabsorbability of the triether and further indicated that it was nontoxic, did not influence the absorption of dietary fat, and mixed intimately with the fat present in colonic contents and feces. The triether that was absorbed was deposited as triether in adipose tissue, liver, and spleen. When administered intraperitoneally to mice, the triether was stored in the tissues and was not metabolized. When the triether was partitioned between an oil phase of triolein or fatty acid and monoglyceride, and an aqueous micellar phase, the triether remained exclusively in the oil phase. The triether appears to be an ideal nonabsorbable oil-phase marker for use in lipid absorption studies.