Intestinally derived lipids: metabolic regulation and consequences--an overview.
Various dietary factors affect postprandial metabolism yet precise mechanisms have not necessarily been pinpointed. The effects of various meal components on postprandial lipemia lead to the following question: do we need a standardized oral lipid tolerance test? A number of transporters, enzymes, receptors and hormones directly influence and act as "gatekeepers" of these processes. Each protein appears to have specific and individual functional roles in the overall process and selected developments in these areas will be reviewed. Within the intestinal cells, FABP2 (fatty acid-binding protein 2) and MTP (microsomal triglyceride transfer protein) are required for the formation of chylomicrons. Niemann-Pick C1-like 1 (NPC1-L1) plays an important role in cholesterol absorption and provides a pharmacological target. Hormones such as GLP1 and GLP2 influence this absorption process. Within the periphery, lipoprotein lipase (LPL) is a key gatekeeper of clearance. Of the massive amounts of fatty acids released by LPL, 36% escape peripheral adipose and muscle uptake and fatty acid overload can result in LPL product inhibition. Acylation stimulating protein (ASP) and insulin are two key hormones in maintaining efficient tissue uptake and re-esterification of fatty acids while TNFalpha negatively influences this process. In both ASP deficient (C3 KO) and C5L2 KO mice, postprandial lipemia increased with reduced adipose tissue storage. This is compensated by increased energy expenditure and muscle lipid oxidation. Clearance of hepatic remnants is controlled through many factors, including SR-B1 and ABCA1. Intestinal, peripheral and hepatic gatekeepers serve important and individual roles in regulating postprandial lipemia and provide potential targets for regulation.
Cianflone
Katherine
K
Department of Biochemistry, McGill University, Montreal, Canada. katherine.cianflone@crhl.ulaval.ca
Paglialunga
Sabina
S
Roy
Christian
C
D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D050171:Dyslipidemias / Q000378:metabolism*; D050556:Fatty Acid-Binding Proteins / Q000378:metabolism*; D005227:Fatty Acids / Q000378:metabolism; D006801:Humans; D007408:Intestinal Absorption / Q000502:physiology*; D007413:Intestinal Mucosa / Q000378:metabolism*; D008861:Microsomes; D019518:Postprandial Period / Q000502:physiology*
D002352:Carrier Proteins; C493404:FABP2 protein, human; D050556:Fatty Acid-Binding Proteins; D005227:Fatty Acids; C106092:microsomal triglyceride transfer protein