PMID- 17405916
OWN - NLM
STAT- MEDLINE
DCOM- 20070419
LR  - 20181201
IS  - 0077-8923 (Print)
IS  - 0077-8923 (Linking)
VI  - 1096
DP  - 2007 Jan
TI  - Upregulation of apolipoprotein B secretion, but not lipid, by tumor necrosis 
      factor-alpha in rat hepatocyte cultures in the absence of extracellular fatty 
      acids.
PG  - 55-69
AB  - Tumor necrosis factor-alpha (TNF-alpha) plays a pivotal role in the host response 
      to infection. Rapidly liberated to the bloodstream, TNF-alpha triggers the 
      production of other cytokines and the acute-phase response. Hypertriglyceridemia 
      is a sepsis hallmark associated with high plasma levels of very low-density 
      lipoprotein (VLDL) particles, partly ascribed to increased hepatic production. 
      The kinetics of the hepatocyte response, the cytokine/s responsible, and the 
      underlying mechanisms are not fully elucidated. VLDL biogenesis is a complex, 
      time-consuming process that depends on lipid availability and microsomal 
      triglyceride transfer protein (MTP) activity for correct apolipoprotein B (apoB) 
      lipidation. Studies were performed to define the direct effect of TNF-alpha on 
      VLDL secretion rate and composition in rat hepatocytes cultured in conditions 
      resembling the fed situation. Increases of 17-24% in the number of VLDL particles 
      secreted and of 44-88% in the cellular levels of apoB mRNA were caused by 5, 20, 
      or 100 ng/mL TNF-alpha in 8 h. Lipoprotein secretion returned to baseline levels 
      in 16 h, whereas TNF-alpha-treated cells continued to exhibit higher apoB 
      transcript levels. The mass of each lipid class in secreted VLDL and of MTP mRNA 
      in cells was not affected by any of the tested TNF-alpha doses or treatment 
      periods. These findings indicate that over a wide range of concentrations, 
      TNF-alpha was capable of inducing sustained upregulation of apoB mRNA expression 
      and transient increase in secretion of its protein, but, apparently, VLDL 
      triglyceride secretion was not a TNF-alpha target under conditions in which fatty 
      acids were not extracellularly provided.
FAU - Bartolome, Nerea
AU  - Bartolome N
AD  - Department of Physiology, Faculty of Medicine and Dentistry, University of the 
      Basque Country, Sarriena s/n, 48940-Leioa, Spain.
FAU - Rodriguez, Lorena
AU  - Rodriguez L
FAU - Martinez, Maria J
AU  - Martinez MJ
FAU - Ochoa, Begona
AU  - Ochoa B
FAU - Chico, Yolanda
AU  - Chico Y
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Ann N Y Acad Sci
JT  - Annals of the New York Academy of Sciences
JID - 7506858
RN  - 0 (Apolipoproteins B)
RN  - 0 (Carrier Proteins)
RN  - 0 (Fatty Acids)
RN  - 0 (Lipids)
RN  - 0 (Lipoproteins)
RN  - 0 (RNA, Messenger)
RN  - 0 (Triglycerides)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 0 (microsomal triglyceride transfer protein)
SB  - IM
MH  - Animals
MH  - Apolipoproteins B/*metabolism
MH  - Carrier Proteins/metabolism
MH  - Fatty Acids/*metabolism
MH  - Female
MH  - Hepatocytes/*cytology
MH  - Kinetics
MH  - Lipids/*chemistry
MH  - Lipoproteins/metabolism
MH  - RNA, Messenger/metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Triglycerides/metabolism
MH  - Tumor Necrosis Factor-alpha/*metabolism
MH  - *Up-Regulation
EDAT- 2007/04/05 09:00
MHDA- 2007/04/20 09:00
CRDT- 2007/04/05 09:00
PHST- 2007/04/05 09:00 [pubmed]
PHST- 2007/04/20 09:00 [medline]
PHST- 2007/04/05 09:00 [entrez]
AID - 1096/1/55 [pii]
AID - 10.1196/annals.1397.070 [doi]
PST - ppublish
SO  - Ann N Y Acad Sci. 2007 Jan;1096:55-69. doi: 10.1196/annals.1397.070.