Mechanism of intestinal lipoprotein overproduction in insulin resistant humans

Triglyceride-rich lipoproteins (TRLs) derived from the intestine are increased in insulin resistant states both in the post-prandial and fasted state and are associated with increased cardiovascular risk. Impaired clearance has long been invoked to explain this accumulation of intestinal TRLs. but more recent studies have highlighted the fact that the production rate apolipoprotein (apo) B-48-containing particles is also increased in insulin resistance and Type 2 diabetes. Recent data also nindicate that the enterocyte, similar to the hepatocyte, overproduces lipoprotein particles in response to an elevation of plasma free fatty acids,. It is not yet clear precisely how much this overproduction of intestinal lipoprotein particles contricutes to the hypertriglyceridemia of insulin resistant states. We speculate that chronic intestinal overproduction of apoB-48 primes the intestine to rapidly and efficiently facilitate the absorption of ingested fat enhancing the assembly and secretion of (C) 2008 Elsevier Ireland Ltd. All rights reserved.