P592The effect of a high fat diet on cardiac and adipose mesenchymal cells.:

Abstract

Mesenchymal cells have been shown to improve contractile function in rodents following myocardial infarction. Here we determined the effect of simply a high fat diet on mesenchymal cells from cardiac and adipose tissues. Mice were fed a high-fat diet (55% fat; HFD,) for 4 months, after which cardiac explant-derived and cardiosphere-derived cells (EDCs, CDCs) were cultured from atrial tissue and the stromal vascular fraction (SVF) was isolated from epididymal fat depots and cultured to give adipose stromal cells (ASCs). Plasma metabolites were measured using an ABX Pentra. Cardiac protein expression was analysed by Western blotting and cells were characterised using qPCR, flow cytometry and immunocytochemistry. High fat-feeding raised fed plasma glucose, cholesterol and insulin levels and decreased plasma lactate, consistent with a type 2 diabetic phenotype. Significantly more ASCs were obtained from HFD animals and ASC numbers correlated with plasma glucose, lactate and cholesterol levels. There was an inverse correlation between the numbers of EDCs and the SVF but no significant differences between total numbers of EDCs or CDCs from chow-fed or HFD mice were found. The SVF and p2 ASCs from HFD mice contained significantly more CD45+ haematopoetic cells, than those from chow-fed mice, whilst p2 ASCs from HFD mice also contained more cells expressing the mesenchymal marker CD105 or the fibroblast marker DDR2. No differences in surface marker expression were observed between CDCs from HFD and chow-fed mice. Thus, whilst a high fat diet does not affect cardiac progenitor cells, it increases the number of fibroblasts and haematopoietic cells within the ASC population. | Surface marker (%) | c-kit | CD105 | CD90 | DDR2 | CD45 | |:------------------ | ---------- | ----------- | ----------- | ---------- | ----------- | | SVF chow | 4.5 ± 0.8 | 4.6 ± 1.4 | 51.0 ± 0.8 | 28.0 ± 1.2 | 58.7 ± 1.6 | | SVF HFD | 4.5 ± 0.8 | 7.4 ± 1.8 | 51.9 ± 1.4 | 26.8 ± 1.7 | 66.6 ± 1.1* | | ASC chow | 1.2 ± 0.2 | 6.9 ± 2.8 | 59.9 ± 2.3 | 3.0 ± 0.7 | 24.0 ± 4.5 | | ASC HFD | 2.0 ± 0.4 | 20.3 ± 4.8* | 49.2 ± 5.1 | 7.0 ± 1.6* | 56.7 ± 4.4* | | CDC chow | 6.7 ± 2.0 | 31.5 ± 4.3 | 54.8 ± 10.6 | 18.4 ± 7.1 | 7.5 ± 0.9 | | CDC HFD | 10.3 ± 4.1 | 31.0 ± 4.0 | 60.0 ± 12.3 | 25.7 ± 7.3 | 8.9 ± 0.7 | * Surface marker expression in SVF, ASCs and CDCs from chow-fed and HFD mice, assessed using flow cytometry. * p < 0.05 vs cells from chow-fed mice. Cell characterisation