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The ability of mammals to resist body fat accumulation is linked to their ability to expand the number and activity of 'brown adipocytes' within white fat depots. Activation of β-adrenergic receptors (β-ARs) can induce a functional 'brown-like' adipocyte phenotype. As cardiac natriuretic peptides (NPs) and β-AR agonists are similarly potent at stimulating lipolysis in human adipocytes, we investigated whether NPs could induce human and mouse adipocytes to acquire brown adipocyte features, including a capacity for thermogenic energy expenditure mediated by uncoupling protein 1 (UCP1). In human adipocytes, atrial NP (ANP) and ventricular NP (BNP) activated PPARγ coactivator-1α (PGC-1α) and UCP1 expression, induced mitochondriogenesis, and increased uncoupled and total respiration. At low concentrations, ANP and β-AR agonists additively enhanced expression of brown fat and mitochondrial markers in a p38 MAPK-dependent manner. Mice exposed to cold temperatures had increased levels of circulating NPs as well as higher expression of NP signaling receptor and lower expression of the NP clearance receptor (Nprc) in brown adipose tissue (BAT) and white adipose tissue (WAT). NPR-C-/-mice had markedly smaller WAT and BAT depots but higher expression of thermogenic genes such as Ucp1. Infusion of BNP into mice robustly increased Ucp1 and Pgc-1α expression in WAT and BAT, with corresponding elevation of respiration and energy expenditure. These results suggest that NPs promote 'browning' of white adipocytes to increase energy expenditure, defining the heart as a central regulator of adipose tissue biology., Introduction The cardiac natriuretic peptides (NPs), atrial NP (ANP) and its ventricular companion (BNP), are key hormones in fluid and hemodynamic homeostasis. Their actions are mediated by binding to NP [...]

Abstract 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: LXRα 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. LXRα, 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.

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 [...]

Here, we report the isolation of a human multipotent adipose-derived stem (hMADS) cell population from adipose tissue of young donors. hMADS cells display normal karyotype; have active telomerase; proliferate >200 population doublings; and differentiate into adipocytes, osteoblasts, and myoblasts. Flow cytometry analysis indicates that hMADS cells are CD44+, CD49b+, CD105+, CD90+, CD13+, Stro-1-, CD34-, CD15-, CD117-, Flk-1-, gly-A-, CD133-, HLA-DR-, and HLA-Ilow. Transplantation of hMADS cells into the mdx mouse, an animal model of Duchenne muscular dystrophy, results in substantial expression of human dystrophin in the injected tibialis anterior and the adjacent gastrocnemius muscle. Long-term engraftment of hMADS cells takes place in nonimmunocompromised animals. Based on the small amounts of an easily available tissue source, their strong capacity for expansion ex vivo, their multipotent differentiation, and their immune-privileged behavior, our results suggest that hMADS cells will be an important tool for muscle cell-mediated therapy. [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]