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 of apolipoprotein (apo) B-48-containing particles is also increased in insulin resistance and Type 2 diabetes. Recent data also indicate 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 contributes 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 intestinal TRL, and hence contributing to post-prandial lipemia.
Duez
Hélène
H
Department of Medicine, Division of Endocrinology, University of Toronto, Toronto, Canada.
Pavlic
Mirjana
M
Lewis
Gary F
GF
D002914:Chylomicrons / Q000378:metabolism; D050171:Dyslipidemias / Q000378:metabolism*; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology*; D007413:Intestinal Mucosa / Q000378:metabolism*; D008074:Lipoproteins / Q000096:biosynthesis*; D019518:Postprandial Period / Q000502:physiology
D002914:Chylomicrons; D008074:Lipoproteins