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Leptin, the 16-kDa peptide hormone product of the ob gene, is produced primarily by adipocytes and was initially thought to exert its effects exclusively through actions on the hypothalamus via distinct leptin receptors termed OB-R. However, recent data show that leptin is produced elsewhere and that receptors are present in many other tissues. Using real-time PCR, we determined whether leptin and its receptors are present in the rat heart and demonstrated regional distribution patterns and gender differences as well as the effect of ischemia and reperfusion. Gene expression of leptin and its receptors (OB-Ra, OB-Rb, and OB-Re) was identified in myocytes and whole heart homogenates from all regions of the heart of male and female rats, with the highest abundance in left and right atria of male and female rats, respectively. No differences in regional distribution of OB-R were evident in male rat hearts. In female rats, expression was highest in right atria for all three isoforms and was significantly greater than in male rats. Ischemia and reperfusion significantly downregulated leptin and OB-R expression, although this was more pronounced in male rat hearts. Leptin release in the coronary effluent was also detected using ELISA, although this was generally unaffected by global ischemia and reperfusion. Our results demonstrate for the first time the presence of the leptin system, including the peptide and its receptors, in all regions of the rat heart. In view of emerging evidence for cardiac effects of leptin, it is proposed that the heart is a target for leptin action and that the peptide modulates function through a paracrine- or autocrine-dependent manner.

Regulation of skeletal remodeling appears to influence the differentiation of multipotent mesenchymal stem cells (MSC) resident in the bone marrow. As murine marrow cultures are contaminated with hematopoietic cells, they are problematic for studying direct effects of mechanical input. Here we use a modified technique to isolate marrow-derived MSC (mdMSC) from adult mice, yielding a population able to differentiate into adipogenic and osteogenic phenotypes that is devoid of hematopoietic cells. In pure mdMSC populations, a daily strain regimen inhibited adipogenic differentiation, suppressing expression of PPAR␥ and adiponectin. Strain increased ␤-catenin and inhibition of adipogenesis required this effect. Under osteogenic conditions, strain activated ␤-catenin signaling and increased expression of WISP1 and COX2. mdMSC were also generated from mice lacking caveolin-1, a protein known to sequester ␤-catenin: caveolin-1 (−/−) mdMSC exhibited retarded differentiation along both adipogenic and osteogenic lineages but retained mechanical responses that involved ␤-catenin activation. Interestingly, caveolin-1 (−/−) mdMSC failed to express bone sialoprotein and did not form mineralized nodules. In summary, mdMSC from adult mice respond to both soluble factors and mechanical input, with mechanical activation of ␤-catenin influencing phenotype. As such, these cells offer a useful model for studies of direct mechanical regulation of MSC differentiation and function. © 2010 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J. Orthop. Res. 28: 1531Res. 28: -1538Res. 28: , 2010 Keywords: stem cell; osteoblast; adipocyte; mechanical loading; caveolin-1Maintenance of the skeleton is a process which must balance diverse inputs that importantly include mechanical information. This information not only influences differentiated cells resident within the bone tissue but may also have critical effects on the fate of multipotent mesenchymal stem cells (MSC) located in the bone marrow. For example, Wnt/␤-catenin signaling, associated with promoting bone formation, 1 appears to primarily impact early events during MSC lineage determination.2 Similarly, mechanical input activates ␤-catenin and promotes expression of Wnt/␤-catenin target genes in bone cells, 3−6 suggesting that loading effects may be most relevant during MSC differentiation. Indeed, recent studies support a mechanical influence on MSC fate in animals: daily exposure to extremely low magnitude mechanical stimulation increases MSC proliferation, with a biasing of the MSC population toward osteogenesis, 7 and mice subjected to a climbing regimen have more osteoblasts and fewer adipocytes in the marrow cavity.8 Conversely, hindlimb unloading increases the potential for adipogenesis in ex vivo marrow cultures. In vitro experimentation has shown that mechanical information promotes the osteogenic potential of precursor cells. 10 In contrast, daily loading of murine embryonic MSC inhibits adipocyte differentiation. 11Loading of primary marrow ce...

The orphan G protein-coupled receptor APJ has been shown to be a coreceptor for human and simian immunodeficiency virus (HIV and SIV) strains. We have determined that some HIV and SIV strains use APJ as a coreceptor to infect the brain-derived NP-2/CD4 cells. Because apelin is an endogenous ligand for the APJ receptor, we examined the inhibitory effects of apelin peptides on HIV infection, and found that the apelin peptides inhibit the entry of some HIV-1 and HIV-2 into the NP-2/CD4 cells expressing APJ. The inhibitory efficiency has been found to be in the order of apelin-36 s apelin-17 s apelin-13 s apelin-12.z 2000 Federation of European Biochemical Societies.