Lipoprotein Lipase Suppression in 3T3-L1 Cells by an Endotoxin-induced Mediator from Exudate Cells
Year: 1984
Type: article
Abstract: A variety of invasive stimuli such as bacterial, parasitic infections, tumor and endotoxemia have been shown to induce a suppression of lipoprotein lipase (LPL) resulting in hypertriglyceridemia. In endotoxin-responsive C3H/HeN mice, the LPL activity in adipose tissue was markedly suppressed 16h after endotoxin administration. In endotoxin-resistant C3H/HeJ mice, the LPL activity was suppressed to a much lesser extent than in C3H/HeN mice. In a remarkable contrast, the blood from C3H/HeN mice obtained 2h after the injection with endotoxin suppressed LPL activity in adipose tissues for both of C3H/HeJ mice and C3H/HeN mice. Accordingly, a transferable factor capable of suppressing LPL would be secreted into the blood of C3H/HeN mice treated with endotoxin. Conditioned medium from peritoneal macrophages of endotoxin-responsive mice cultured in the presence of endotoxin suppressed adipose tissue LPL in C3H/HeJ mice also. The transferable factor which appeared in blood and suppressed LPL activity, therefore, appeared to be secreted by macrophages in response to endotoxin. In addition, the factor did not directly inhibit LPL activity nor accelerate the rate of decay of LPL. These results have indicated that the factor suppresses LPL activity by inhibiting its synthesis or processing in the cells.Employing 3T3-L1 cell culture, the mechanism by which the factor suppresses LPL activity has been studied. The factor suppressed LPL activity in 3T3-L1 adipocyte in culture. In view of the known requierment of insulin and glucose for the maximal experssion of LPL activity, the effect of the factor on insulin insulin receptor interaction, the glucose uptake and protein synthesis were studied. Neither insulin binding to insulin receptor nor glucose transport was affected by the factor. However, the incorporation of 35S-methionine into protein in particulate fraction of 3T3-L1 cells decreased by 50% after the cells were exposed to the factor; little change was observed in the incorporation into the soluble fraction. Comparison of the proteins obtained from cells with or without endotoxin treatment on SDS polyacrylamide gel electrophoresis has demonstrated that the factor modulates the synthesis of proteins in both of soluble and particulate fractions in a selective manner.On the basis of these results, one of the primary effect of the factor seems most likely to be exerted on protein synthesis.
Language: English
Subfield: Cardiology and Cardiovascular Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: diamond
OpenAlex ID: W2605669283