Overexpression of apolipoprotein C-III decreases secretion of dietary triglyceride into lymph.

Abstract

Apolipoprotein C‐III (apoC‐III) is not only predominantly synthesized by the liver but also by the small intestine. Because apoC‐III is secreted from the intestine on the chylomicron along with lipid absorption, we questioned whether apoC‐III might play a role in intestinal lipid absorption and/or transport. Using both wild‐type (WT) and apoC‐III transgenic (apoC‐III Tg) mice, we showed that apoC‐III Tg mice have decreased lymphatic lipid transport compared with WT mice in response to an intraduodenal infusion of radiolabeled lipid. This is associated with accumulation of radiolabeled lipids in the luminal compartment of the apoC‐III Tg mice, indicating delayed lipid uptake from the lumen. The total amount of radioactive lipids in the mucosal compartment did not differ between apoC‐III Tg and WT mice, but the lipid distribution analysis indicated a predominance of free fatty acids and monoacylglycerol in the mucosa of apoC‐III Tg mice, implying impaired esterification capacity. Thus, the mechanisms underlying the reduced lymphatic lipid transport in apoC‐III Tg mice involve both a delayed lipid uptake into enterocytes, as well as impaired esterification to form triglyceride in the mucosa. These data document a novel role for apoC‐III in the uptake, re‐esterification, and lymphatic transport of dietary lipids in the intestine.