Elevation of tumor necrosis factor-alpha 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)-alpha induces intestinal-derived apolipoprotein B (apoB)48-containing very low-density lipoprotein (VLDL) production in hamsters after fat loading and whether TNF-alpha disturbs the related mRNA expression in inflammatory, insulin and lipoprotein signaling pathways in primary enterocytes. In vivo TNF-alpha 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 VLDL(1) particles by TNF-alpha. TNF-alpha infusion increased intestinal production of chylomicron and VLDL(1)-apoB48 in postprandial (fat load) states. Following TNF-alpha-treatment in enterocytes, there was enhanced gene expression of Il1alpha and beta, 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-alpha also induced Cd36 and peroxisome proliferators-activated receptor (Ppar)gamma 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-alpha stimulates the postprandial overproduction of apoB48-containing chylomicrons and VLDL(1) particles by disturbing intestinal gene expression of the inflammatory, insulin and lipoprotein pathways. These findings provide mechanistic links among the inflammatory factor, TNF-alpha, intestinal inflammatory/insulin insensitivity and the overproduction of intestinal apoB48-containing lipoproteins.
Qin
Bolin
B
Diet, Genomics, and Immunology Laboratory, Beltsville Human Nutrition Research Center, Agricultural Research Service, US Department of Agriculture, Beltsville, Building 307C, 10300 Baltimore Avenue, Beltsville, MD 20705-2350, USA.
Dawson
Harry
H
Anderson
Richard A
RA
D000818:Animals; D053283:Apolipoprotein B-48 / Q000096:biosynthesis*; D001483:Base Sequence; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D002914:Chylomicrons / Q000096:biosynthesis; D006224:Cricetinae; D017931:DNA Primers / Q000235:genetics; D020895:Enterocytes / Q000187:drug effects / Q000378:metabolism*; D015870:Gene Expression / Q000187:drug effects; D066298:In Vitro Techniques; D018836:Inflammation Mediators / Q000378:metabolism; D007328:Insulin / Q000378:metabolism; D055504:Insulin Receptor Substrate Proteins / Q000235:genetics; D008079:Lipoproteins, VLDL / Q000096:biosynthesis*; D008297:Male; D008647:Mesocricetus; D047495:PPAR gamma / Q000235:genetics; D051059:PTEN Phosphohydrolase / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011972:Receptor, Insulin / Q000235:genetics; D051122:Scavenger Receptors, Class B / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects; D051780:Sterol Regulatory Element Binding Protein 1 / Q000235:genetics / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology
D053283:Apolipoprotein B-48; D002352:Carrier Proteins; D002914:Chylomicrons; D017931:DNA Primers; D018836:Inflammation Mediators; D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; D008079:Lipoproteins, VLDL; D047495:PPAR gamma; D012333:RNA, Messenger; C495124:SCARB1 protein, human; D051122:Scavenger Receptors, Class B; D051780:Sterol Regulatory Element Binding Protein 1; D014409:Tumor Necrosis Factor-alpha; C106092:microsomal triglyceride transfer protein; D011972:Receptor, Insulin; D051059:PTEN Phosphohydrolase