This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff.
The aim of the project is to examine the involvement of the melanocortin system in the regulation of lipolysis and blood pressure and to characterise possible alternative signalling pathways of MCRs in adipocytes. In house studies in a mouse 3T3 cell line differentiated to adipocytes indicates that the MC5 receptor and possibly also the MC2 receptor are involved in direct stimulation of lipolysis (manuscript in preparation), and furthermore preliminary data indicates that other signalling pathways than cAMP are involved in the melanocortin mediated lipolysis of mouse adipocytes. Examination of mouse primary adipocytes and fat tissue is the next step in order to obtain a better understanding of the MCR distribution and the biological effects of the melanocortin system in white adipose tissue. As significant species differences with regard to lipolysis have been described for the melanocortin system (Boston &Cone 1996a), it is also important to characterise the expression pattern of the five MCR's in fat tissue from other species (incl. humans) in order to identify the species that is most optimal for studying these effects in the development of MC4R agonists as obesity drugs. A possible side effect described for the MC4R is increased blood pressure, and the effect of the melanocortin system on blood pressure are being investigated in telemeterised in vivo models, especially MC3 and MC4 knockout mice. Furthermore, it should be established whether these potential species differences exist with regard to blood pressure as well as lipolysis.
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