The metabolic effects of interleukin 1 beta on human bone marrow adipocytes.
We have recently shown that interleukin 1 beta (IL-1 beta) directly reduces the number of adipocytes in cultures of human bone marrow (BM) stromal cells. The aim of the present study was to establish the mechanisms involved in the IL-1 effect and thereby assess its importance in BM pathophysiology. Direct morphological observation showed that individual adipocytes lost their fat in the presence of IL-1 beta and regained it when the cytokine was withdrawn. These morphological observations were supported by metabolic studies using [14]acetate as a precursor of storage fat. These metabolic studies showed that IL-1 beta inhibited the incorporation of label into triglycerides. In addition, the cytokine enhanced the release of radioactivity from prelabelled adipocytes and reduced their triglyceride stores. It was therefore concluded that IL-1 beta can both inhibit lipogenesis and stimulate lipolysis in BM adipocytes. Forskolin (an adenylate cyclase activator) produced lipolytic effect similar to those of IL-1 beta, while indomethacin (an inhibitor of prostaglandin [PG] production) fully blocked the release of radioactivity induced by IL-1 beta and greatly increased triglyceride synthesis. However, IL-1 beta was still able to decrease triglyceride synthesis in the presence of indomethacin. These results indicate that a prostaglandin-dependent increase in cAMP is important to in the lipolytic effects of IL-1 beta but that the anti-lipogenic effects of the cytokine are, at least in part, independent of PG synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)
Delikat
S E
SE
Department of Haemotology, Royal Liverpool University Hospital, UK.
Galvani
D W
DW
Zuzel
M
M
D000085:Acetates / Q000378:metabolism; D000262:Adenylyl Cyclases / Q000378:metabolism; D000273:Adipose Tissue / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D001854:Bone Marrow Cells; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology; D015232:Dinoprostone / Q000378:metabolism; D006410:Hematopoiesis / Q000502:physiology; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D007375:Interleukin-1 / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D050356:Lipid Metabolism; D008066:Lipolysis / Q000187:drug effects; D014280:Triglycerides / Q000378:metabolism
D000085:Acetates; D007375:Interleukin-1; D014280:Triglycerides; D005576:Colforsin; D000262:Adenylyl Cyclases; D015232:Dinoprostone; D007213:Indomethacin