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

Abstract

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 Il1 α 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.