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Background: 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). Results: 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: LXR α and phospholipid transfer protein (PLTP) for adipogenesis, the nuclear receptor COUP-TF1 and one uncharacterized gene, TMEM135 for osteoblastogenesis. PLTP was secreted during both early and late time points of hMADS adipocyte differentiation. LXR α, COUP-TF1, and the transmembrane protein TMEM135 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. Conclusion: 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Fatty acids enter the cultured cardiac cells from chick embryo through two mechanisms, one involving a saturable process, the other resembling passive diffusion. Studies of the saturable component, at fixed concentrations of palmitate or of oleate and at increasing concentrations of albumin, show that this protein increases the rate of palmitate uptake with a maximum at palmitate/albumin molar ratios between 7 and 10 while it decreases the rate of oleate uptake under ali conditions. Albumin cannot be replaced by other serum proteins; its effect is specific to saturated fatty acids, can be mimicked by the detergent Tween 40 and involves the binding of the fatty acid to the protein, prior to its delivery to the cell. Both with labelled saturated and unsaturated fatty acids the presence of albumin lowers the proportion of unesterified fatty acids and enhances the proportion of esterified fatty acids recovered in the cardiac cell after uptake. A similar effect of albumin was also found with hepatocytes and permanent cell lines. A specific role for serum albumin is presented, which assumes a 'dispersing' effect of this protein towards dimers (or higher aggregates) of saturated fatty acids and the entry of fatty acids into the cell as monomers. [ABSTRACT FROM AUTHOR]