Mattes RD. Brief oral stimulation, but especially oral fat exposure, elevates serum triglycerides in humans. Am J Physiol Gastrointest Liver Physiol 296: G365-G371, 2009. First published December 12, 2008 doi:10.1152/ajpgi.90591.2008.-Oral exposure to dietary fat results in an early initial spike, followed by a prolonged elevation, of serum triglycerides in humans. The physiological and pathophysiological implications remain unknown. This study sought to determine the incidence of the effect, the required fat exposure duration, and its reliability. Thirty-four healthy adults participated in four to six response-driven trials held at least a week apart. They reported to the laboratory after an overnight fast, a catheter was placed in an antecubital vein, and a blood sample was obtained. Participants then ingested 50 g of safflower oil in capsules with 500 ml of water within 15 min to mimic a high fat meal but without oral fat exposure. Blood was collected 0,10,20,30, 40, 50, 60, 120, 240, 360, and 480 min after capsule ingestion with different forms (full fat, nonfat, none) and durations of oral fat exposures (10 s, 5 min, 20 min, and/or 2 h). A triglyceride response (increase of triglyceride Ͼ10 mg/dl within 30 min) was observed in 88.2%, 70.5%, and 50% of participants with full-fat, nonfat, and no oral exposure, respectively. Test-retest reliability was 75% with full-fat exposure but only 45.4% with nonfat exposure. Full-fat and nonfat exposures led to comparable significant elevations of triglyceride over no oral stimulation with 10-s exposures, but full fat led to a greater rise than nonfat with 20 min of exposure. These data indicate that nutritionally relevant oral fat exposures reliably elevate serum triglyceride concentrations in most people.taste; lipid; cardiovascular disease; chemosensory; cephalic phase ASIDE FROM CONTRIBUTING TO the sensory appeal of foods, oral exposure to dietary fat elicits physiological responses involved with nutrient processing in the gut. Oral exposure to linoleic acid elicits pancreatic exocrine secretion in mice (7), and linoleic, linolenic, and oleic acids have the same effect in rats (9,14). Oral fat exposure in rats also slows (27) and aids regulation of gastric emptying (12) and prolongs the postprandial elevation of serum triacylglycerol (TAG) (27). Similarly, in humans, oral fat exposure elicits a range of effects including modulation of gut peptide secretion (8), appetitive sensations (8, 30), preferred fat levels in foods (16), energy intake (4) and postprandial lipemia (18 -20, 25). The latter effect is reported to be biphasic. The first phase is, in part, due to mobilization of lipid stored, presumably in the enterocyte, from the previous meal (5,20,25,29). The second phase reflects sensory exposure effects on absorption of the lipid providing the initial oral stimulation, de novo synthesis and secretion of lipid particles, and/or clearance of lipid from the blood. To date, work on oral fat exposure and postprandial TAG concentrations in humans has involved exposu...