Priming of Polymorphonuclear Granulocytes by Lipopolysaccharides and Its Complexes With Lipopolysaccharide Binding Protein and High Density Lipoprotein

1990 ◽  
Vol 47 (2) ◽  
pp. 97-104 ◽  
Author(s):  
Klaus Vosbeck ◽  
Peter Tobias ◽  
Heinz Mueller ◽  
Rodger A. Allen ◽  
Karl-E. Arfors ◽  
...  
Author(s):  
Safa’a Ali Al-Qudah ◽  
Violet Kasabri ◽  
Mohammad Issa Saleh ◽  
Maysa Suyagh ◽  
Sundos AlAlawi ◽  
...  

Abstract Background Metabolic syndrome (MetS) and prediabetes (preDM) have crosslinked pathophysiologies with central obesity and insulin resistance (IR). This study aimed to compare and correlate nesfatin and lipopolysaccharide binding protein (LBP) plasma levels, adiposity, atherogenicity and hematological indices between non-diabetic MetS, newly diagnosed drug naive pre-diabetic MetS patients vs. normoglycemic lean controls. Materials and methods In a cross-sectional study, 29 apparently healthy controls, 29 non-diabetic MetS subjects and 30 preDM-MetS patients were recruited. Results The LBP level (ng/mL) was substantially higher in both MetS (non- and pre-diabetic) groups compared to healthy controls. In contrast, circulating level of nesfatin (pg/mL) was lower, though not significantly; in both pre-diabetic and non-diabetic MetS patients compared to lean normoglycemic controls. No correlation was found between nesfatin and LBP in MetS pool (n = 59). Remarkably unlike blood indices; adiposity indices [body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR), waist-to-height (WHtR) ratio, hip circumference (HC), body adiposity index (BAI), visceral adiposity index (VAI), lipid accumulation product (LAP) but not conicity index (CI)], atherogenicity indices [(atherogenicity index of plasma (AIP = Log10(TG/HDL-C ratio)), low density lipoprotein cholesterol to high density lipoprotein cholesterol ratio (LDL-C/HDL-C) and non-high density lipoprotein cholesterol (non-HDL-C)] were substantially higher in both MetS (non- and pre-diabetic) groups vs. those of controls. Exceptionally pronounced and proportional nesfatin-DBP and LBP-BAI correlations were identified in total MetS pool (both non-diabetic and pre-diabetic). Conclusions Nesfatin and LBP can be potential targets and surrogate biomarkers to use as putative prognostic/predictive tools for the prevention and treatment for MetS and related disorders.


2019 ◽  
Vol 295 (10) ◽  
pp. 2900-2912 ◽  
Author(s):  
Amitabh V. Nimonkar ◽  
Stephen Weldon ◽  
Kevin Godbout ◽  
Darrell Panza ◽  
Susan Hanrahan ◽  
...  

Lipoprotein lipase (LPL) is central to triglyceride metabolism. Severely compromised LPL activity causes familial chylomicronemia syndrome (FCS), which is associated with very high plasma triglyceride levels and increased risk of life-threatening pancreatitis. Currently, no approved pharmacological intervention can acutely lower plasma triglycerides in FCS. Low yield, high aggregation, and poor stability of recombinant LPL have thus far prevented development of enzyme replacement therapy. Recently, we showed that LPL monomers form 1:1 complexes with the LPL transporter glycosylphosphatidylinositol-anchored high-density lipoprotein–binding protein 1 (GPIHBP1) and solved the structure of the complex. In the present work, we further characterized the monomeric LPL/GPIHBP1 complex and its derivative, the LPL–GPIHBP1 fusion protein, with the goal of contributing to the development of an LPL enzyme replacement therapy. Fusion of LPL to GPIHBP1 increased yields of recombinant LPL, prevented LPL aggregation, stabilized LPL against spontaneous inactivation, and made it resistant to inactivation by the LPL antagonists angiopoietin-like protein 3 (ANGPTL3) or ANGPTL4. The high stability of the fusion protein enabled us to identify LPL amino acids that interact with ANGPTL4. Additionally, the LPL–GPIHBP1 fusion protein exhibited high enzyme activity in in vitro assays. Importantly, both intravenous and subcutaneous administrations of the fusion protein lowered triglycerides in several mouse strains without causing adverse effects. These results indicate that the LPL–GPIHBP1 fusion protein has potential for use as a therapeutic for managing FCS.


2007 ◽  
Vol 5 (4) ◽  
pp. 279-291 ◽  
Author(s):  
Anne P. Beigneux ◽  
Brandon S.J. Davies ◽  
Peter Gin ◽  
Michael M. Weinstein ◽  
Emily Farber ◽  
...  

Sign in / Sign up

Export Citation Format

Share Document