Mechanisms by which food intake elevates circulating levels of hyaluronan in humans

OBJECTIVES. Plasma hyaluronan is a potentially useful clinical test, especially in liver disease. It rises after eating, but mechanisms by which this occurs are not known. The study aimed at defining the effect of different food and liquid intake on plasma hyaluronan and to address mechanisms. DESIGN. The effects on plasma hyaluronan of ingestion of high-fat and low-fat meals, glucose solution, and saline, and of intravenous metoclopramide and oral cisapride were defined in healthy fasted subjects by serial measurements over 5 h. Hyaluronan was measured by a radiometric assay. RESULTS. After test meals and glucose ingestion, plasma hyaluronan rose to 1.7-13 times the fasting levels in 11 healthy volunteers. Peak values were observed in most subjects 45-90 min after ingestion and reached levels in six subjects that might suggest the presence of hepatic fibrosis or cirrhosis. No change occurred after ingestion of 0.48 L iso-osmotic NaCl solution, equal in bulk to the glucose solution. Stimulation of gastrointestinal motility with metoclopramide had no effect but oral cisapride induced a pattern of elevated plasma hyaluronan which mimicked that induced by foodstuffs. CONCLUSIONS. Displacement of hyaluronan from gastrointestinal tissues prevails over the increased clearance expected from elevated portal blood flow. The heightened flux of tissue fluid necessary to displace tissue hyaluronan is best explained by vasodilatation in response to ingestion of nutrients, and subsequent increase in intestinal lymph flow, rather than by fluid absorption, together with gut contraction. The discriminating value of plasma hyaluronan in clinical practice may be greatly enhanced by sampling in fasted subjects at rest.