Interleukin-6, but not tumour necrosis factor-alpha, increases lipogenesis in rat hepatocyte primary cultures.
The Kupffer-cell products interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-alpha) have been shown to stimulate hepatic lipogenesis in vivo. Studies were performed to define the direct effects of these cytokines on lipogenesis in primary-culture rat hepatocytes. Hepatocytes were cultured in the presence of IL-6 or TNF-alpha for periods of 24-72 h. IL-6 increased hepatocyte protein content per microgram of DNA. IL-6 also caused a dose- and time-dependent induction of hepatocyte capacity for incorporation of [2-14C]pyruvate into fatty acids (56% increase by 12.5 ng/ml IL-6 after 72 h of cytokine exposure). This increase in cellular lipogenic capacity was confirmed by using 3H2O incorporation into fatty acids as tracer. TNF-alpha did not increase hepatocyte lipogenesis. In contrast with studies in vivo, neither IL-6 nor TNF-alpha had any acute (2 h of exposure) effects on rates of lipogenesis. Both IL-6 and TNF-alpha are known to increase macrophage prostaglandin synthesis acutely. The prostaglandin E agonist misoprostol free acid (0.1 microM) acutely increased hepatocyte lipogenic rates by 14%. Thus, IL-6 can directly induce hepatocyte lipogenic capacity, and E-series prostaglandins can antagonize the acute inhibition of lipogenesis by glucagon. The observations provide further evidence for the role of Kupffer-cell products in the regulation of hepatocyte metabolism.
Brass
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Department of Medicine, Case Western Reserve University, Cleveland, OH 44106-4981.
Vetter
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D000818:Animals; D002478:Cells, Cultured; D015850:Interleukin-6 / Q000494:pharmacology*; D007700:Kinetics; D007728:Kupffer Cells / Q000187:drug effects / Q000378:metabolism; D008055:Lipids / Q000096:biosynthesis*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism*; D051381:Rats; D011994:Recombinant Proteins / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D015850:Interleukin-6; D008055:Lipids; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha