Endotoxin suppresses rat hepatic: Low density lipoprotein receptor expression

Liao, Wei; Rudling, Mats; Angelin, Bo

doi:10.1016/0021-9150(95)96688-o

Cited by 6 publications

(13 citation statements)

References 33 publications

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“…As reported by other investigators, LPS treatment resulted in a marked decrease in LDL receptor protein levels in the liver (~60% decrease) (Figure 1A) [2, 3]. Figure 1B shows the effect of LPS on hepatic LDL receptor mRNA levels.…”

Section: Resultssupporting

confidence: 76%

“…In rodents, LPS administration, a frequently used model for gram negative bacterial infection, increases VLDL and LDL levels while decreasing HDL levels [1]. Studies have shown that LPS administration decreases LDL receptor protein levels in the liver, which could lead to the decreased clearance of circulating LDL and account for the increase in serum LDL levels [2, 3]. However, the effects of LPS administration on LDL receptor mRNA expression in the liver have been variable with decreases in LDL receptor mRNA levels observed soon after LPS administration followed by increases in LDL receptor mRNA levels at later time points [2–4].…”

Section: Introductionmentioning

confidence: 99%

“…However, the effects of LPS administration on LDL receptor mRNA expression in the liver have been variable with decreases in LDL receptor mRNA levels observed soon after LPS administration followed by increases in LDL receptor mRNA levels at later time points [2–4]. In contrast, the decrease in LDL receptor protein levels occurs rapidly after LPS administration and persists for an extended period of time [2, 3]. These results suggest that while the initial decrease in hepatic LDL receptors could be due to a decrease in LDL receptor mRNA levels the decrease observed at later time points must be due to other regulatory pathways.…”

Section: Introductionmentioning

confidence: 99%

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Inflammation stimulates the expression of PCSK9

Feingold

Moser

Shigenaga

et al. 2008

Biochemical and Biophysical Research Communications

192

137

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Inflammation induces marked changes in lipid and lipoprotein metabolism. Proprotein convertase subtilisin kexin 9 (PCSK9) plays an important role in regulating LDL receptor degradation. Here we demonstrate that LPS decreases hepatic LDL receptor protein but at the same time hepatic LDL receptor mRNA levels are not decreased. We therefore explored the effect of LPS on PCSK9 expression. LPS results in a marked increase in hepatic PCSK9 mRNA levels (4 hours-2.5 fold increase; 38 hours-12.5 fold increase). The increase in PCSK9 is a sensitive response with 1 ug LPS inducing a ½ maximal response. LPS also increased PCSK9 expression in the kidney. Finally, zymosan and turpentine, other treatments that induce inflammation, also stimulated hepatic expression of PCSK9. Thus, inflammation stimulates PCSK9 expression leading to increased LDL receptor degradation and decreasing LDL receptors thereby increasing serum LDL, which could have beneficial effects on host defense.

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Section: Resultssupporting

confidence: 76%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Inflammation stimulates the expression of PCSK9

Feingold

Moser

Shigenaga

et al. 2008

Biochemical and Biophysical Research Communications

192

137

View full text Add to dashboard Cite

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“…14 The protein concentration in the membrane preparation was assayed, 15 using reagents from Bio-Rad Laboratories (Richmond, CA). The membrane preparation was mixed with nonreducing loading buffer, separated on 6% sodium dodecyl sulfate (SDS)-polyacrylamide gels, and electrotransferred onto 0.45-µm nitrocellulose filters (Schleicher and Schuell, Keene, NH) 8,14,16,17 as described. The filters were incubated for 1 hour with 125 I-labeled rabbit ␤-migrating VLDL (5 µg/mL) and extensively washed.…”

mentioning

confidence: 99%

Endotoxin suppresses mouse hepatic low-density lipoprotein-receptor expression via a pathway independent of the toll-like receptor 4

1999

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Endotoxin provokes an inflammatory state in the infected host. C3H/HeJ mice are tolerant to endotoxin because of an Lps gene mutation. Recent studies have identified that this gene encodes the Toll-like receptor 4. Endotoxin also induces hyperlipidemia and suppresses hepatic low-density lipoprotein (LDL)-receptor expression. In the current study, we investigated whether a defective Lps gene would impair the hepatic LDL-receptor response to endotoxin in C3H/HeJ mice. Eighteen hours after an intraperitoneal injection of endotoxin, the hepatic LDL-receptor expression and the plasma lipoprotein pattern were analyzed. Endotoxin increased plasma triglyceride and apoE in very low-density lipoproteins (VLDL) and intermediate-density lipoproteins, and decreased apoAI in high-density lipoproteins (HDL) in the endotoxin-sensitive mice (C3H/HeN), but not in the endotoxin-resistant mice (C3H/HeJ). These data indicate that a defective Lps gene impairs the endotoxin signaling to alter these lipoproteins. However, the hepatic LDL-receptor response to endotoxin in the endotoxin-resistant mice was similar to that in the endotoxin-sensitive mice. Thus, at a dose of 5 g/mouse, endotoxin reduced hepatic LDL-receptor expression by 35% in C3H/HeN mice and by 52% in C3H/HeJ mice. At a dose of 50 g/mouse, endotoxin reduced hepatic LDL-receptor expression by 61% in C3H/ HeN mice and by 63% in C3H/HeJ mice. It is concluded that endotoxin suppresses hepatic LDL-receptor expression in vivo via a pathway independent of the Toll-like receptor 4. (HEPATOLOGY 1999;30:1252-1256.) Endotoxin is one of the most active bacterial products that mediate gram-negative bacterial septic shock. Endotoxin also profoundly alters the metabolism of plasma lipids and lipoproteins, leading to a hyperlipidemic state. 1,2 In endotoxin-treated animals, plasma triglycerides, and to a lesser extent plasma cholesterol levels, are increased. The endotoxin-induced hyperlipidemia is characterized by accumulation of lipids within very low-density lipoproteins (VLDL) and low-density lipoproteins (LDL), whereas high-density lipopro-teins (HDL) are decreased or unchanged. Both a reduced clearance of VLDL, caused by inhibition of lipoprotein lipase, and a stimulation of hepatic VLDL production contribute to the endotoxin-induced hypertriglyceridemia. This hyperlipid-emic response of the infected host to endotoxin is generally regarded as a part of the host-defense mechanism. 3,4 Other mechanisms may also operate in the development of endo-toxin-induced hyperlipidemia. Thus, in HepG2 cells endo-toxin interferes with cellular LDL uptake by forming complexes with LDL. 5,6 Injection of endotoxin together with 125 I-LDL inhibits 125 I-LDL clearance in rats. 7 Recently, we have shown that endotoxin reduces rat hepatic LDL-receptor expression and increases circulating apoB-containing lipopro-teins in vivo. 8 Endotoxin-induced inhibition of LDL-receptor expression is thus probably also involved in the pathogenesis of endotoxin-induced hyperlipidemia. C3H/HeJ mice are resistant to end...

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“…However, fat mobilization greatly exceeds oxidation under these conditions, resulting in considerable cycling (5,6). This could be due to inhibition of lipoprotein lipase (7)(8)(9), an increase in very low density lipoprotein production (10), decreased low-density lipoprotein clearance (11), or decreased oxidation of fatty acids (12). Proinflammatory cytokines increase adipose tissue lipolysis (13) and hepatic triglyceride (TG) release (14) but can impair lipoprotein lipase activity (15) and fatty acid oxidation (16,17).…”

mentioning

confidence: 99%

Oxidation of Intravenous Lipid in Infants and Children With Systemic Inflammatory Response Syndrome and Sepsis

et al. 2007

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During sepsis in adults, fat becomes a preferred fuel; however, oxidation may be impaired relative to the circulating fatty acid levels. Little is known about the ability of infants and children to oxidize lipids during systemic inflammation (SIRS) and sepsis. The aim of this study was to examine the oxidation of exogenous lipid in these patients. Sixteen patients with SIRS/sepsis and eight controls with no evidence of sepsis were studied by indirect calorimetry during an i.v. lipid utilization test (1 h of 0.3 g/kg/h glucose followed by 3 h of 0.1 g/kg/h glucose plus 0.15 g/kg/h lipid). The respiratory quotient (RQ) (1.0 for carbohydrate utilization and 0.7 for fat utilization) was measured. Results were compared by repeatedmeasures analysis of variance (ANOVA), paired or unpaired t tests.

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Endotoxin suppresses rat hepatic: Low density lipoprotein receptor expression

Cited by 6 publications

References 33 publications

Inflammation stimulates the expression of PCSK9

Inflammation stimulates the expression of PCSK9

Endotoxin suppresses mouse hepatic low-density lipoprotein-receptor expression via a pathway independent of the toll-like receptor 4

Oxidation of Intravenous Lipid in Infants and Children With Systemic Inflammatory Response Syndrome and Sepsis

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