Restricted accessResearch articleFirst published online 2010-2
Elevation of tumor necrosis factor- α induces the overproduction of postprandial intestinal apolipoprotein B48-containing very low-density lipoprotein particles: evidence for related gene expression of inflammatory,insulin and lipoprotein signaling in enterocytes
The aim of this study was to determine whether systemic elevation of tumor necrosis factor (TNF)-α induces intestinal-derived apolipoprotein B (apoB)48-containing very low-density lipoprotein (VLDL) production in hamsters after fat loading and whether TNF-α disturbs the related mRNA expression in inflammatory, insulin and lipoprotein signaling pathways in primary enterocytes. In vivo TNF-α and Triton-WR1339 infusion, Western blotting and reverse transcriptase-polymerase chain reaction were combined to explore the mechanisms underlying intestinal overproduction of apoB48-containing chylomicrons and VLDL1 particles by TNF-α. TNF-α infusion increased intestinal production of chylomicron and VLDL1-apoB48 in postprandial (fat load) states. Following TNF-α-treatment in enterocytes, there was enhanced gene expression of Il1α and β, Il6 and Tnf and decreased mRNA levels of components of the insulin signaling pathway including the insulin receptor (Ir), Ir substrate-1 and 2, PI3 k, and Akt, but increased phosphatase and tensin homolog deleted on chromosome ten (Pten) protein and mRNA expression. TNF-α also induced Cd36 and peroxisome proliferators-activated receptor (Ppar)γ expression, as well as microsomal triglyceride transfer protein (Mtp) protein and mRNA, but suppressed the sterol regulatory element binding protein (Srebp)1c protein and mRNA level. Systemic elevation of TNF-α stimulates the postprandial overproduction of apoB48-containing chylomicrons and VLDL1 particles by disturbing intestinal gene expression of the inflammatory, insulin and lipoprotein pathways. These findings provide mechanistic links among the inflammatory factor, TNF-α, intestinal inflammatory/insulin insensitivity and the overproduction of intestinal apoB48-containing lipoproteins.
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