20 research outputs found

    The Adipose Renin-Angiotensin System Modulates Systemic Markers of Insulin Sensitivity and Activates the Intrarenal Renin-Angiotensin System

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    Background. The adipose tissue renin-angiotensin system (RAS) contributes to regulation of fat mass and may also impact systemic functions such as blood pressure and metabolism. Methods and results. A panel of mouse models including mice lacking angiotensinogen, Agt (Agt-KO), mice expressing Agt solely in adipose tissue (aP2-Agt/Agt-KO), and mice overexpressing Agt in adipose tissue (aP2-Agt) was studied. Total body weight, epididymal fat pad weight, and circulating levels of leptin, insulin, and resistin were significantly decreased in Agt-KO mice, while plasma adiponectin levels were increased. aP2-Agt mice exhibited increased adiposity and plasma leptin and insulin levels compared to wild type (WT) controls. Angiotensinogen and type I Ang II receptor protein levels were also elevated in kidney of aP2-Agt mice. Conclusion. These findings demonstrate that alterations in adipose RAS activity significantly impact both local and systemic physiology in a way that may contribute to the detrimental health effects of obesity

    Comparative transcriptomics of human multipotent stem cells during adipogenesis and osteoblastogenesis

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    <p>Abstract</p> <p>Background</p> <p>A reciprocal relationship between bone and fat development in osteoporosis is clinically well established. Some of the key molecular regulators involved in this tissue replacement process have been identified. The detailed mechanisms governing the differentiation of mesenchymal stem cells (MSC) – the key cells involved – are however only now beginning to emerge. In an attempt to address the regulation of the adipocyte/osteoblast balance at the level of gene transcription in a comprehensive and unbiased manner, we performed a large-scale gene expression profiling study using a unique cellular model, human multipotent adipose tissue-derived stem cells (hMADS).</p> <p>Results</p> <p>The analysis of 1606 genes that were found to be differentially expressed between adipogenesis and osteoblastogenesis revealed gene repression to be most prevalent prior to commitment in both lineages. Computational analyses suggested that this gene repression is mediated by miRNAs. The transcriptional activation of lineage-specific molecular processes in both cases occurred predominantly after commitment. Analyses of the gene expression data and promoter sequences produced a set of 65 genes that are candidates for genes involved in the process of adipocyte/osteoblast commitment. Four of these genes were studied in more detail: <it>LXRα </it>and phospholipid transfer protein (<it>PLTP</it>) for adipogenesis, the nuclear receptor <it>COUP-TF1 </it>and one uncharacterized gene, <it>TMEM135 </it>for osteoblastogenesis. <it>PLTP </it>was secreted during both early and late time points of hMADS adipocyte differentiation. <it>LXRα</it>, <it>COUP-TF1</it>, and the transmembrane protein <it>TMEM135 </it>were studied in primary cultures of differentiating bone marrow stromal cells from healthy donors and were found to be transcriptionally activated in the corresponding lineages.</p> <p>Conclusion</p> <p>Our results reveal gene repression as a predominant early mechanism before final cell commitment. We were moreover able to identify 65 genes as candidates for genes controlling the adipocyte/osteoblast balance and to further evaluate four of these. Additional studies will explore the precise role of these candidate genes in regulating the adipogenesis/osteoblastogenesis switch.</p

    Current agri-environmental policies dismiss varied perceptions and discourses on management of traditional rural biotopes

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    Traditional rural biotopes (TRBs) are threatened habitats that host significant biodiversity and several ecosystem services, and depend on active management such as low-intensity grazing. The current study explores private landowners’ decision-making on TRB management and abandonment within a social-ecological system framework. We provide insight into supporting resilience of TRB systems in the face of agricultural modernization. Using a mixed methods approach with content analysis and Q analysis, we demonstrate that TRB management fosters cultural, biological, aesthetic, and utilitarian values. These are reflected in different ways through conservationist’s, profit-oriented farmer’s, landscape manager’s, and landscape admirer’s discourses on TRB management. Overall, management reinforces landowners’ place attachment, and reflects an approach to landscapes as spatial representations of cultural heritage and identity over multiple generations. Landowners consider TRB pasturage and its social-ecological outcomes motivating and rewarding. Giving up grazing cattle and perceived bureaucracy of national agri-environment scheme contribute to TRB abandonment. Landowners point out that current policies detach TRB management from what is seen as “regular agriculture”, and the focus on monetary compensation bypasses the multiple values tied to TRB management. Based on our results, we suggest that promoting TRBs requires reconfiguring the current arrangement of remedial management payments and adopting a more participatory governance approach. Locally, resilience of TRB systems relies on the connections between landowners and landscapes that foster sense of place and landscape identity, which can be supported by knowledge sharing and collaborative grazing efforts among landowners.peerReviewe
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