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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
1990-8-8
pubmed:abstractText
Tumor necrosis factor (TNF) increases serum triglycerides in rats by increasing de novo hepatic fatty acid synthesis and very low density lipoprotein production. We have recently shown that several other cytokines increase hepatic fatty acid synthesis in the mouse. We now explore the mechanism by which these cytokines increase de novo lipogenesis and the interactions between cytokines in fed mice. TNF administration results in increased hepatic levels of citrate, the primary allosteric activator of acetyl-CoA carboxylase, which is the major rate-limiting enzyme for fatty acid synthesis. The TNF-induced increase in citrate occurs within 15 min of administration, early enough to account for the acute rise in hepatic fatty acid synthesis seen by 30 min after TNF administration. IL-1, which also increases hepatic fatty acid synthesis, produces similar increases in hepatic citrate levels. In contrast, another potent stimulator of hepatic fatty acid synthesis, interferon-alpha (IFN alpha), has no effect on hepatic citrate levels. There were no acute effects of TNF or IL-1 on the activation state of acetyl-CoA carboxylase. A trend toward an increase in the activation state of acetyl-CoA carboxylase was seen after IFN alpha administration. Low doses of TNF and IL-1 given in combination show no synergy while maximal doses are not additive. In contrast, when a low dose of either TNF or IL-1 is combined with a low dose of IFN alpha, there is synergy in stimulating hepatic fatty acid synthesis. A maximal dose of TNF or IL-1 and a high dose of IFN alpha produce a further increase in hepatic fatty acid synthesis. These data support the concept that there are two classes of cytokines that stimulate hepatic fatty acid synthesis, those that can increase hepatic citrate levels and those that cannot.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0013-7227
pubmed:author
pubmed:issnType
Print
pubmed:volume
127
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
46-54
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1990
pubmed:articleTitle
Evidence for two classes of cytokines that stimulate hepatic lipogenesis: relationships among tumor necrosis factor, interleukin-1 and interferon-alpha.
pubmed:affiliation
Department of Medicine, University of California, San Francisco.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, U.S. Gov't, P.H.S., Research Support, U.S. Gov't, Non-P.H.S., Research Support, Non-U.S. Gov't