ORCID Profile
0000-0003-4680-9422
Current Organisation
Geneva University
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Publisher: eLife Sciences Publications, Ltd
Date: 16-04-2018
DOI: 10.7554/ELIFE.34114
Abstract: Circadian regulation of transcriptional processes has a broad impact on cell metabolism. Here, we compared the diurnal transcriptome of human skeletal muscle conducted on serial muscle biopsies in vivo with profiles of human skeletal myotubes synchronized in vitro. More extensive rhythmic transcription was observed in human skeletal muscle compared to in vitro cell culture as a large part of the in vivo mRNA rhythmicity was lost in vitro. siRNA-mediated clock disruption in primary myotubes significantly affected the expression of ~8% of all genes, with impact on glucose homeostasis and lipid metabolism. Genes involved in GLUT4 expression, translocation and recycling were negatively affected, whereas lipid metabolic genes were altered to promote activation of lipid utilization. Moreover, basal and insulin-stimulated glucose uptake were significantly reduced upon CLOCK depletion. Our findings suggest an essential role for the circadian coordination of skeletal muscle glucose homeostasis and lipid metabolism in humans.
Publisher: Proceedings of the National Academy of Sciences
Date: 20-08-2018
Abstract: Earlier studies suggested that particles are released from the macrophage plasma membrane, but the mechanism has been unclear. We found that filopodia of macrophages release large numbers of vesicular particles. Nanoscale secondary ion mass spectrometry revealed that these particles are enriched in cholesterol, including the “accessible” pool of cholesterol detectable by the cholesterol-binding protein. The cholesterol content of macrophage particles increased when the cells were loaded with cholesterol and could be depleted by incubating the cells with high-density lipoproteins. Our studies suggest that the release of particles by macrophages could be one mechanism for cholesterol efflux and that particles could be an intermediate in the movement of cholesterol to high-density lipoproteins.
Publisher: Proceedings of the National Academy of Sciences
Date: 25-09-2017
Abstract: Our experiments provide the analysis of lipid metabolite circadian oscillations in a cellular system synchronized in vitro, suggesting cell-autonomous diurnal changes in lipid profiles independent of feeding. Moreover, our work represents a comprehensive comparison between the lipid composition of human skeletal muscle derived from sedentary healthy adults, receiving hourly isocaloric solutions, and human primary skeletal myotubes cultured in vitro. A substantial number of lipid metabolites, in particular membrane lipids, exhibited oscillatory patterns in muscle tissue and in myotube cells, where they were blunted upon cell-autonomous clock disruption. As lipid oscillations in skeletal muscle membrane lipids may impact on insulin signaling and on the development of insulin resistance, studying the temporal lipid composition of human muscle is therefore of utmost importance.
Publisher: eLife Sciences Publications, Ltd
Date: 09-03-2018
Publisher: Elsevier BV
Date: 07-2008
Location: Switzerland
Location: Switzerland
Location: Switzerland
No related grants have been discovered for Howard Riezman.