No abstract

Cytokines like tumor necrosis factor (TNF), interferon-gamma (IFN-gamma), and interleukin-1 (IL-1) are known to interfere with the differentiation of cultured cell lines of adipocyte precursors. In the present study, the effect of mouse and rat IFN-gamma, as well as human IL-1 beta, was investigated on rodent preadipocytes in primary cultures, either in the presence of fetal bovine serum (FBS, 10%) or in serum-free defined medium. IFN-gamma exerted an antiproliferative action that was more pronounced when cells reached confluency than during the growth phase of the culture. Morphological observation and quantifications of undifferentiated and differentiating cells revealed that IFN-gamma caused a decrease in the proportion of cells devoid of lipid droplets which would correspond to fibroblast-like cells, whereas preadipocytes remained unaffected. IFN-gamma induced a marked retardation of adipoconversion, resulting in a partial inhibition of lipoprotein lipase (LPL) activity and a severe decrease in glycerol-3-phosphate dehydrogenase (GPDH) activity. The antiproliferative and anti-LPL effects of IFN-gamma were neutralized by adding anti-IFN-gamma antibodies, while these antibodies prevented only partially the depressing effect of IFN-gamma on GPDH activity. Contrary to IFN-gamma, IL-1 beta slightly enhanced the proliferation in preadipocyte cultures. IL-1 beta also depressed adipoconversion, inhibited markedly LPL activity, and partially reduced GPDH activity. These results show that the influence of cytokines on adipoconversion observed in preadipocyte cell lines can be found in normal preadipocytes in culture.

Summary ― The development of external, internal, inter-and intramuscular adipose tissues was compared in Pietrain (lean)

We report a multi-objective de novo design study driven by synthetic tractability and aimed at the prioritization of computer-generated 5-HT2B receptor ligands with accurately predicted target-binding affinities. Relying on quantitative bioactivity models we designed and synthesized structurally novel, selective, nanomolar, and ligand-efficient 5-HT2B modulators with sustained cell-based effects. Our results suggest that seamless amalgamation of computational activity prediction and molecular design with microfluidics-assisted synthesis enables the swift generation of small molecules with the desired polypharmacology.

The stroma-vascular fraction (SVF) of inguinal and epididymal fat pads of 4 week-old rats was studied by electron microscopy. Among the various cell types, endothelial cells and preadipocytes were found in both SVF, while mesothelial cells were only detected in the epididymal SVF. The resulting heterogeneity of primary culture and the adipoconversion of the fat cell precursors were studied in a serum-supplemented medium enriched with insulin (14.5 nM) and exogeneous triglycerides. Despite the heterogeneity of the inoculum, the primary cultures were rather homogeneous, fat cell precursors being the main cell type. Distinctive contaminant fibroblast-like cells were observed in both cultures, whereas epithelial-like cells, which correspond most probably to mesothelial cells, were only found in epididymal cultures. Differentiation of fat cell precursors was assessed by the appearance of lipoprotein lipase (LPL) and glycerol-3-phosphate dehydrogenase (GPDH). LPL activity was found in the same level in cells of both deposits while GPDH activity was elevated in inguinal vs epididymal derived stroma-vascular ceils. The different adipose conversion pattern of both cultures was confirmed by morphological quantification : the maturation of epididymal fat cell precursors was faster but less extensive. These differences could be related mainly to regional localization rather than to different maturation of the two fat deposits. preadipocyte / adipose tissue / stroma-vascular fraction / regional differences