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Showing papers by "Arthur H. Moser published in 1998"


Journal ArticleDOI
TL;DR: It is demonstrated that serum PON activity decreases following endotoxin (LPS) administration in Syrian hamsters, suggesting that the decrease in PON could be another factor linking the acute phase response with increased atherogenesis.

241 citations


Journal ArticleDOI
TL;DR: Results indicate that LPS and cytokines stimulate hepatic sphingolipid synthesis, which results in an altered structure of circulating lipoproteins and may promote atherogenesis.
Abstract: Alterations in triglyceride and cholesterol metabolism often accompany inflammatory diseases and infections We studied the effects of endotoxin (lipopolysaccharide [LPS]) and cytokines on hepatic sphingolipid synthesis, activity of serine palmitoyltransferase (SPT), the first and rate-limiting enzyme in sphingolipid synthesis, and lipoprotein sphingolipid content in Syrian hamsters Administration of LPS induced a 2-fold increase in hepatic SPT activity The increase in activity first occurred at 16 hours, peaked at 24 hours, and was sustained for at least 48 hours Low doses of LPS produced maximal increases in SPT activity, with half-maximal effect seen at approximately 03 microg LPS/100 g body weight LPS increased hepatic SPT mRNA levels 2-fold, suggesting that the increase in SPT activity was due to an increase in SPT mRNA LPS treatment also produced 75% and 25-fold increases in hepatic sphingomyelin and ceramide synthesis, respectively Many of the metabolic effects of LPS are mediated by cytokines Interleukin 1 (IL-1), but not tumor necrosis factor, increased both SPT activity and mRNA levels in the liver of intact animals, whereas both IL-1 and tumor necrosis factor increased SPT mRNA levels in HepG2 cells IL- produced a 3-fold increase in SPT mRNA in HepG2 cells, and the half-maximal dose was 2 ng/mL IL-1 also increased the secretion of sphingolipids into the medium Analysis of serum lipoprotein fractions demonstrated that very low density lipoprotein, intermediate density lipoprotein, and low density lipoprotein isolated from animals treated with LPS contained significantly higher amounts of ceramide, glucosylceramide, and sphingomyelin Taken together, these results indicate that LPS and cytokines stimulate hepatic sphingolipid synthesis, which results in an altered structure of circulating lipoproteins and may promote atherogenesis

163 citations


Journal ArticleDOI
TL;DR: The results demonstrate that LPS decreased FATP and FAT mRNA expression in adipose tissue, heart, skeletal muscle, brain, spleen, and kidney, tissues in which FA uptake and/or oxidation is decreased during sepsis.
Abstract: The cloning of two novel fatty acid (FA) transport proteins, FA transport protein (FATP) and FA translocase (FAT), has recently been reported; however, little is known about their in vivo regulatio...

140 citations


Journal ArticleDOI
TL;DR: A role for UCP2 in the heat production and increased energy expenditure that occurs during infection is suggested.

83 citations


Journal ArticleDOI
TL;DR: It is suggested that MTP mRNA down-regulation does not contribute significantly to the cytokine-induced effects on lipid metabolism, and that an intact AP-1 and/or HNF-1 regulatory element are crucial for the IL-1 regulation of MTP gene expression.

65 citations


Journal ArticleDOI
TL;DR: The results indicate that LPS and cytokines decrease ACS1 mRNA expression and ACS activity in tissues where FA uptake and/or oxidation is decreased during sepsis, and this may support the reesterification of peripherally derived FA for triglyceride synthesis.
Abstract: Acyl-CoA synthetase (ACS) catalyzes the activation of fatty acids (FA) to acyl-CoA esters, which are further metabolized in either anabolic or catabolic pathways Endotoxin [lipopolysaccharide (LPS

55 citations