Impaired response of VLDL lipid and apoB secretion to endotoxin in the fasted rat liver.
Bacterial infection elicits hypertriglyceridemia attributed to increased hepatic production of very low-density lipoprotein (VLDL) particles and decreased peripheral metabolism. The mechanisms underlying VLDL overproduction in sepsis are as yet unclear, but seem to be fed/fasted state-dependent. To learn more about this, we investigated hepatocytes isolated from fasted rats, made endotoxic by 1 mg/kg lipopolysaccharide (LPS) injection, for their ability to secrete the VLDL protein and lipid components. The results were then related to lipogenesis markers and expression of genes critical to VLDL biogenesis. Endotoxic rats showed increased levels of serum VLDL-apoB (10-fold), -triglyceride (2-fold), and -cholesterol (2-fold), whereby circulating VLDL were lipid-poor particles. Similarly, VLDL-apoB secretion by isolated endotoxic hepatocytes was approximately 85% above control, whereas marginal changes in the output of VLDL-lipid classes occurred. This was accompanied by a substantial rise in apoB and a moderate rise in MTP mRNA levels, but with basal de novo formation and efficiency of secretion of triglycerides, cholesterol and cholesteryl esters. These results indicate that during periods of food restriction, endotoxin does not enhance lipid provision to accomplish normal lipidation of overproduced apoB molecules, though this does occur to a sufficient extent to pass the proteasome checkpoint and secretion of lipid-poor, type 2 VLDL takes place.
Aspichueta
Patricia
P
Department of Physiology, University of the Basque Country Medical School, Bilbao, Spain.
Pérez-Agote
Begoña
B
Pérez
Silvia
S
Ochoa
Begoña
B
Fresnedo
Olatz
O
D000818:Animals; D001055:Apolipoproteins B / Q000378:metabolism*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D002784:Cholesterol / Q000378:metabolism; D005260:Female; D005508:Food Deprivation; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism; D008070:Lipopolysaccharides / Q000633:toxicity*; D008079:Lipoproteins, VLDL / Q000378:metabolism*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018805:Sepsis / Q000378:metabolism; D014280:Triglycerides / Q000378:metabolism
D001055:Apolipoproteins B; D002352:Carrier Proteins; D008070:Lipopolysaccharides; D008079:Lipoproteins, VLDL; D012333:RNA, Messenger; D014280:Triglycerides; C106092:microsomal triglyceride transfer protein; D002784:Cholesterol