Proteomic profiling of intestinal prechylomicron transport vesicle (PCTV)-associated proteins in an animal model of insulin resistance (94 char).
Intestinal overproduction of apolipoprotein B (apoB)-48-containing chylomicrons is increasingly recognized as an underlying factor in metabolic dyslipidemia commonly observed in insulin-resistant states. Enhanced chylomicron assembly and secretion has been documented in animal models of insulin resistance, but the underlying mechanistic factors are unknown. Chylomicron assembly occurs through a series of complex vesicular interactions involving prechylomicron transport vesicles (PCTVs), which transport lipids from the endoplasmic reticulum (ER) to the Golgi. We report proteomic profiles of PCTVs isolated from the enteric ER in the small intestine of the fructose-fed hamster, an established model of diet-induced insulin resistance. Using 2D gel electrophoresis and tandem mass spectrometry, PCTVs were characterized and proteomic profiles of PCTV-associated proteins from insulin-resistant and control enterocytes were developed, with the intention of identifying proteins involved in insulin signaling attenuation and lipoprotein overproduction. A number of PCTV-associated proteins were found to be differentially expressed including microsomal triglyceride transfer protein (MTP), apoB-48, Sar1 and VAMP7. We postulate that altered expression of Sar1 and MTP may contribute to increased chylomicron assembly in the fructose-fed hamster. These findings have increased our understanding of the intracellular assembly and transport of nascent chylomicrons and potential cellular factors responsible for lipoprotein overproduction in insulin-resistant states.
Wong
Diana M
DM
Molecular Structure and Function, Division of Clinical Biochemistry, Department of Pediatric Laboratory Medicine, Research Institute, The Hospital for Sick Children, 555 University Ave, Toronto, ON, Canada.
Webb
Jennifer P
JP
Malinowski
Paul M
PM
Xu
Elaine
E
Macri
Joseph
J
Adeli
Khosrow
K
D000818:Animals; D053298:Chylomicron Remnants / Q000737:chemistry* / Q000378:metabolism*; D006224:Cricetinae; D020869:Gene Expression Profiling / Q000379:methods; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology*; D007413:Intestinal Mucosa / Q000378:metabolism*; D008297:Male; D008647:Mesocricetus; D023421:Models, Animal; D010449:Peptide Mapping; D020543:Proteome / Q000737:chemistry / Q000378:metabolism; D022161:Transport Vesicles / Q000378:metabolism*
D053298:Chylomicron Remnants; D020543:Proteome