Acute effects of interleukin 1 alpha and 6 on intermediary metabolism in freshly isolated rat hepatocytes.
Using hepatocytes in suspension, freshly isolated from adult male fed rats, we studied the acute influence of recombinant human interleukins 1 alpha, 2 and 6 on glycogen and fatty acid metabolism. By far the largest effects were observed with interleukin-1 alpha: short incubations (up to 60 min) sufficed to depress glycogen synthesis in a dose-dependent manner, while the rates of glycogenolysis and glycolysis were increased as indicated by the release of glucose and lactate. Interleukin-6 acted similarly, though being much less effective on a molar basis, whereas interleukin-2 only caused a small increase in lactate production. In hepatocytes from 24h-starved rats interleukin-1 alpha caused a minor stimulation of gluconeogenesis. Although neither fatty acid synthesis nor oxidation of fatty acids in quiescent hepatocytes from fed rats was significantly affected by interleukins, interleukin-1 alpha was able to cause appreciable inhibition of fatty acid synthesis in hepatocytes from regenerating liver (isolated 22h after partial hepatectomy). It is concluded (i) that interleukins, in particular interleukin-1 alpha, acutely promote hepatic glucose release, and (ii) that transition of adult hepatocytes from a quiescent into a proliferatory state allows the occurrence of rapid effects of interleukin-1 alpha on fatty acid metabolism.
Vaartjes
W J
WJ
Laboratory of Veterinary Biochemistry, Utrecht University, The Netherlands.
de Haas
C G
CG
Houweling
M
M
D000818:Animals; D002478:Cells, Cultured; D005227:Fatty Acids / Q000096:biosynthesis / Q000378:metabolism; D005943:Gluconeogenesis / Q000187:drug effects; D006498:Hepatectomy; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology*; D007376:Interleukin-2 / Q000494:pharmacology; D015850:Interleukin-6 / Q000494:pharmacology*; D007700:Kinetics; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008112:Liver Glycogen / Q000096:biosynthesis / Q000378:metabolism; D008115:Liver Regeneration; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D011994:Recombinant Proteins / Q000494:pharmacology; D012016:Reference Values
D005227:Fatty Acids; D007375:Interleukin-1; D007376:Interleukin-2; D015850:Interleukin-6; D008112:Liver Glycogen; D011994:Recombinant Proteins