scholarly journals Aortic cholesterol accumulation correlates with systemic inflammation but not hepatic and gonadal adipose tissue inflammation in low-density lipoprotein receptor null mice

2013 ◽  
Vol 33 (12) ◽  
pp. 1072-1082 ◽  
Author(s):  
Shu Wang ◽  
Bradley Miller ◽  
Nirupa R. Matthan ◽  
Zeynep Goktas ◽  
Dayong Wu ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Systemic Inflammation ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Low Density ◽  
Lipoprotein Receptor ◽  
Adipose Tissue Inflammation ◽  
Cholesterol Accumulation ◽  
Density Lipoprotein Receptor ◽  
Aortic Cholesterol

scholarly journals Peroxisome proliferator-activated receptor-γ regulates the expression and function of very-low-density lipoprotein receptor

2010 ◽  
Vol 298 (1) ◽  
pp. E68-E79 ◽  
Author(s):  
Huan Tao ◽  
Srikanth Aakula ◽  
Naji N. Abumrad ◽  
Tahar Hajri
Keyword(s):  
Adipose Tissue ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Very Low Density Lipoprotein ◽  
Low Density ◽  
Lipoprotein Receptor ◽  
Low Density Lipoprotein Receptor ◽  
Density Lipoprotein Receptor ◽  
And Function

Very-low-density lipoprotein receptor (VLDLR) is a member of the low-density receptor family, highly expressed in adipose tissue, heart, and skeletal muscle. It binds apolipoprotein E-triglyceride-rich lipoproteins and plays a significant role in triglyceride metabolism. PPARγ is a primary regulator of lipid metabolism in adipocytes and controls the expression of an array of genes involved in lipid trafficking in adipocytes. However, it is not known whether VLDLR is also under the control of PPARγ. In this study, we investigated the role of PPARγ in the regulation of VLDLR expression and function in vivo and in vitro. During the differentiation of 3T3-L1 preadipocytes, the levels of VLDLR protein and mRNA increased in parallel with the induction of PPARγ expression and reached maximum in mature adipocytes. Treatment of differentiated adipocytes with PPARγ agonist pioglitazone upregulated VLDLR expression in dose- and time-dependent manners. In contrast, specific inhibition of PPARγ significantly downregulated the protein level of VLDLR. Induction of VLDLR is also demonstrated in vivo in adipose tissue of wild-type (WT) mice treated with pioglitazone. In addition, pioglitazone increased plasma triglyceride-rich lipoprotein clearance and increased epididymal fat mass in WT mice but failed to induce similar effects in vldlr−/−mice. These results were further corroborated by the finding that pioglitazone treatment enhanced adipogenesis and lipid deposition in preadipocytes of WT mice, while its effect in VLDLR-null preadipocytes was significantly blunted. These findings provide direct evidence that VLDLR expression is regulated by PPARγ and contributes in lipid uptake and adipogenesis.

Abstract 386: Thrombin Inhibition by Dabigatran Reduces the Amount of Pro-Inflammatory CD11c-Positive Macrophages in Visceral Adipose Tissue of Low-Density Lipoprotein Receptor-Deficient Mice

2015 ◽  
Vol 35 (suppl_1) ◽  
Author(s):  
Kathrin Feldmann ◽  
Maria Grandoch ◽  
Stefan Lehr ◽  
Jens W Fischer
Keyword(s):  
Adipose Tissue ◽  
Visceral Adipose Tissue ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Low Density ◽  
Lipoprotein Receptor ◽  
Thrombin Inhibition ◽  
Diet Induced Obesity ◽  
Density Lipoprotein Receptor ◽  
Visceral Adipose

Thrombin is involved in inflammatory processes. In obesity, chronic low-grade inflammation promotes the development of insulin resistance and diabetes mellitus type 2 (T2DM) which strongly drive atherosclerosis. Patients with T2DM exhibit increased circulating levels of tissue factor as well as thrombin-antithrombin complexes. Aim of the present study was to analyse potential effects of thrombin inhibition by dabigatran on adipose tissue inflammation in a mouse-model of diet-induced obesity and atherosclerosis. Female, 10 weeks old low-density lipoprotein receptor-deficient (LDLR-/-) mice received a Western-type diet containing 5 mg/g dabigatran or matching placebo for 20 weeks. Flow cytometric analysis of the stromal vascular fraction revealed a reduction in pro-inflammatory macrophages (CD11b+F4/80+CD11c+) in visceral adipose tissue of dabigatran-treated animals (control 8.490 ± 1.996, dabigatran 3.606 ± 0.8884 CD11c+ macrophages/mg adipose tissue, n = 21), while the number of anti-inflammatory CD11c- macrophages was not changed. mRNA expression in the visceral adipose tissue as well as plasma concentrations of the pro-inflammatory cytokines interleukin (IL) 1 beta and IL 6 (quantitative real-time PCR (qPCR), multiplex immunoassay) were reduced in dabigatran-treated animals. No differences in body-weight gain and the amount of body fat (NMR measurement) were observed. Glucose tolerance and insulin resistance did not differ between groups, either. In vitro no direct influence of thrombin on macrophage polarization was detectable in bone marrow-derived macrophages (flow cytometry, qPCR). However, first results indicate that stimulation of the cells with conditioned medium from thrombin-treated, differentiated preadipocytes (3T3L1 cells) enhances M1 polarization of macrophages (flow cytometry). In conclusion, thrombin inhibition by dabigatran promotes an anti-inflammatory phenotype in adipose tissue macrophages in a mouse model of diet-induced obesity and atherosclerosis, probably resulting from a changed expression profile of adipocyte cytokines. These effects might contribute to the known anti-atherosclerotic effects of thrombin inhibition in this model.

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