High Density Lipoprotein Protects against Polymicrobe-induced Sepsis in Mice*

Guo, Ling; Ai, Junting; Zheng, Zhong; Howatt, Deborah A.; Daugherty, Alan; Huang, Bin; Li, Xiang-An

doi:10.1074/jbc.m112.442699

Cited by 117 publications

(96 citation statements)

References 49 publications

(48 reference statements)

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“…After reaching the blood stream, virtually all LPS molecules are rapidly complexed with circulating proteins and lipoproteins. When complexed with HDL [44], LPS is cleared by SR-BI in hepatocytes [45] and in other cell types such as macrophages and monocytes, as recently described [46]. The clearance of LPS through SR-BI efficiently determines the magnitude of the inflammatory response, and it has already been shown that SAA is associated with impairment of SR-BI [20].…”

Section: Discussionmentioning

confidence: 99%

Serum amyloid A links endotoxaemia to weight gain and insulin resistance in mice

et al. 2016

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Aims/hypothesis Pre-adipocytes and adipocytes are responsive to the acute phase protein serum amyloid A (SAA). The combined effects triggered by SAA encompass an increase in preadipocyte proliferation, an induction of TNF-α and IL-6 release and a decrease in glucose uptake in mature adipocytes, strongly supporting a role for SAA in obesity and related comorbidities. This study addressed whether SAA depletion modulates weight gain and insulin resistance induced by a high-fat diet (HFD). Methods Male Swiss Webster mice were fed an HFD for 10 weeks under an SAA-targeted antisense oligonucleotide (ASO SAA ) treatment in order to evaluate the role of SAA in weight gain. Results With ASO SAA treatment, mice receiving an HFD did not differ in energy intake when compared with their controls, but were prevented from gaining weight and developing insulin resistance. The phenotype was characterised by a lack of adipose tissue expansion, with low accumulation of epididymal, retroperitoneal and subcutaneous fat content and decreased inflammatory markers, such as SAA3 and toll-like receptor (TLR)-4 expression, as well as macrophage infiltration into the adipose tissue. Furthermore, a metabolic status similar to chow-fed mice counterparts could be observed, with equivalent levels of leptin, adiponectin, IGF-I, SAA, fasting glucose and insulin, and remarkable improvement in glucose and insulin tolerance test profiles. Surprisingly, the expected HFD-induced metabolic endotoxaemia was also prevented by the ASO SAA treatment. Conclusions/interpretationThis study provides further evidence of the role of SAA in weight gain and insulin resistance. Moreover, we also suggest that beyond its proliferative and inflammatory effects, SAA is part of the lipopolysaccharide signalling pathway that links inflammation to obesity and insulin resistance.

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Section: Discussionmentioning

confidence: 99%

Serum amyloid A links endotoxaemia to weight gain and insulin resistance in mice

et al. 2016

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“…HDL, as well as other plasma lipoproteins (LDL, TG-rich lipoproteins), can bind and neutralize Gram-negative bacterial LPS as well as Gram-positive bacterial lipoteichoic acid (LTA) Murch et al 2007). ApoA-I knockout mice, which lack HDL, exhibit decreased LPS neutralization in the serum compared with serum from control mice (Guo et al 2013); overexpression of apoA-I moderately improves survival compared to controls, suggesting that HDL elevation may protect against septic death. In endotoxemic rats, in which LPS has been infused after HDL administration, HDLs attenuate LPS-induced organ damage accompanied by lower TNF-α and nitric oxide production (Lee et al 2007).…”

Section: Interaction Of Hdl With Lps and Gram-negative Bacteriamentioning

confidence: 99%

HDL in Infectious Diseases and Sepsis

Pirillo

Catapano

Norata

2014

Handbook of Experimental Pharmacology

179

163

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“…We had similar observations (data not shown). HDL regulates the expression of adhesion molecules (69), and a deficiency of HDL has been shown to impair the recruitment of leukocytes to peritoneal cavity following CLP (65). To elucidate if hepatic SR-BI affects leukocyte recruitment in sepsis, we quantified peritoneal neutrophils and inflammatory monocytes with flow cytometry in Scarb1 I179N mice and C57BL/6J mice.…”

Section: /G Tissue In Scarb1mentioning

confidence: 99%

Hepatic Scavenger Receptor BI Protects Against Polymicrobial-induced Sepsis through Promoting LPS Clearance in Mice

Guo

Zheng

Ai³

et al. 2014

Journal of Biological Chemistry

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Background: We utilized Scarb1I179N mice, a model deficient in hepatic SR-BI, to determine the role of hepatic SR-BI in sepsis. Results: Upon cecal ligation and puncture (CLP), Scarb1 I179N mice had a 3.5-fold increase in fatality associated with an impaired LPS clearance. Conclusion: Hepatic SR-BI protects against sepsis through promoting LPS clearance. Significance: Promoting hepatic SR-BI-mediated LPS clearance may provide a therapeutic approach for sepsis.

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High Density Lipoprotein Protects against Polymicrobe-induced Sepsis in Mice*

Cited by 117 publications

References 49 publications

Serum amyloid A links endotoxaemia to weight gain and insulin resistance in mice

Serum amyloid A links endotoxaemia to weight gain and insulin resistance in mice

HDL in Infectious Diseases and Sepsis

Hepatic Scavenger Receptor BI Protects Against Polymicrobial-induced Sepsis through Promoting LPS Clearance in Mice

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