Adaptation of intestinal production of apolipoprotein A-IV during chronic feeding of lipid

We examined the effect of daily fat supplementation on intestinal gene expr ession and protein synthesis and plasma levels of apolipoprotein A-IV (apo A-IV). Rats were fasted overnight and then given intragastric bolus infusio n of either saline or fat emulsion after 0,1, 2, 4, 8, or 16 days of simila r daily feedings. Four hours after the final saline or fat infusion, plasma and jejunal mucosa were harvested; plasma levels of apo A-IV, triglyceride s, and leptin were measured, as well as mucosal apo A-IV mRNA levels and bi osynthesis of apo A-IV protein. In response to fat, plasma apo A-IV showed an initial 40% increase compared with saline-injected control rats; with co ntinued daily fat feeding, the plasma A-IV response showed rapid and progre ssive diminution such that by 4 days, plasma A-IV was not different between fat-and saline-fed groups. Jejunal mucosal apo A-IV synthesis and mRNA lev els also showed time-dependent refractoriness to fat feeding. However, the kinetics of this effect were considerably slower than in the case of plasma , requiring 16 days for completion. There was no correlation between plasma leptin or triglyceride levels and intestinal apo A-IV synthesis or plasma apo A-IV. These results indicate rapid, fat-induced, posttranslational adap ation of plasma apo A-IV levels and a slower, but similarly complete pretra nslational adaptation of intestinal apo A-IV production, which are independ ent of plasma levels of leptin.