Glucagon-like peptide-2 increases intestinal lipid absorption and chylomicron production via CD36.
OBJECTIVE
Excessive postprandial lipemia is a prevalent condition that results from intestinal oversecretion of apolipoprotein B48 (apoB48)-containing lipoproteins. Glucagon-like peptide-2 (GLP-2) is a gastrointestinal-derived intestinotropic hormone that links nutrient absorption to intestinal structure and function. We investigated the effects of GLP-2 on intestinal lipid absorption and lipoprotein production.


METHODS
Intestinal lipid absorption and chylomicron production were quantified in hamsters, wild-type mice, and Cd36(-/-) mice infused with exogenous GLP-2. Newly synthesized apoB48 was metabolically labelled in primary hamster jejunal fragments. Fatty acid absorption was measured, and putative fatty acid transporters were assessed by immunoblotting.


RESULTS
Human GLP-2 increased secretion of the triglyceride (TG)-rich lipoprotein (TRL)-apoB48 following oral administration of olive oil to hamsters; TRL and cholesterol mass each increased 3-fold. Fast protein liquid chromatography profiling indicated that GLP-2 stimulated secretion of chylomicron/very low-density lipoprotein-sized particles. Moreover, GLP-2 directly stimulated apoB48 secretion in jejunal fragments cultured ex vivo, increased expression of fully glycosylated cluster of differentiation 36/fatty acid translocase (CD36), and induced intestinal absorption of [(3)H]triolein. The ability of GLP-2 to increase intestinal lipoprotein production was lost in Cd36(-/-) mice.


CONCLUSIONS
GLP-2 stimulates intestinal apoB48-containing lipoprotein secretion, possibly through increased lipid uptake, via a pathway that requires CD36. These findings suggest that GLP-2 represents a nutrient-dependent signal that regulates intestinal lipid absorption and the assembly and secretion of TRLs from intestinal enterocytes.
Hsieh
Joanne
J
Molecular Structure and Function, Hospital for Sick Children, Toronto, Ontario, Canada.
Longuet
Christine
C
Maida
Adriano
A
Bahrami
Jasmine
J
Xu
Elaine
E
Baker
Christopher L
CL
Brubaker
Patricia L
PL
Drucker
Daniel J
DJ
Adeli
Khosrow
K
D000818:Animals; D053283:Apolipoprotein B-48 / Q000097:blood / Q000378:metabolism; D018955:CD36 Antigens / Q000378:metabolism; D002914:Chylomicrons / Q000378:metabolism*; D006224:Cricetinae; D004042:Dietary Fats, Unsaturated / Q000008:administration & dosage; D050612:Fatty Acid Transport Proteins / Q000378:metabolism; D005227:Fatty Acids / Q000378:metabolism; D053767:Glucagon-Like Peptide 2 / Q000494:pharmacology / Q000502:physiology*; D007408:Intestinal Absorption / Q000187:drug effects / Q000502:physiology*; D007583:Jejunum / Q000378:metabolism*; D050356:Lipid Metabolism; D008074:Lipoproteins / Q000737:chemistry / Q000378:metabolism*; D008297:Male; D008647:Mesocricetus; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D014280:Triglycerides / Q000737:chemistry / Q000378:metabolism*; D014304:Triolein / Q000378:metabolism
D053283:Apolipoprotein B-48; D018955:CD36 Antigens; D002914:Chylomicrons; D004042:Dietary Fats, Unsaturated; D050612:Fatty Acid Transport Proteins; D005227:Fatty Acids; D053767:Glucagon-Like Peptide 2; D008074:Lipoproteins; D014280:Triglycerides; C030087:lipoprotein triglyceride; D014304:Triolein