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Multicellular clustering of adipocytes is associated with increased leptin expression and secretion



Multicellular clustering of adipocytes is associated with increased leptin expression and secretion



FASEB Journal 15(4): A77, March 7



Leptin is a hormone expressed in adipose tissue that acts as a sensor for adiposity. The amount of leptin secreted is a function of the size and number of adipocytes, however, it is unclear how adipocytes "know" how big they are. The size of the cytoskeleton increases in proportion to adipocyte volume. It is posited that cell signaling elements associated with the cytoskeleton and engaged by cell-cell or cell-matrix interactions may provide the signal for determining the size of the adipocyte and, thereby regulate leptin expression and secretion. In support of this idea, leptin changes during tissue morphogenesis in vivo and with dissociation of tissue into isolated cells in vitro. To further evaluate this idea we measured leptin secretion from Matrigel-cultured adipocytes as they organized into multicellular clusters over several days. It is thought that multicellular clustering reflects events associated with adipose tissue morphogenesis in vivo. Cell cultures were maintained in DMEM with 10% adult calf serum that was changed daily. Leptin in the adipocyte-conditioned media was measured by RIA. The amount of leptin increased several fold between the first and fourth day in culture, as cells formed extensive plexuses and clusters, and leveled off thereafter. The rise in leptin secretion was delayed and greatly blunted in adipocyte cultures from older rats (> 15 weeks old) which exhibit far less multicellular clustering. Leptin secretion was also attenuated in the presence of rapamycin, which inhibits multicellular clustering. Time-dependent increases in leptin secretion were associated with both an increase in leptin mRNA concentrations and a rapamycin-sensitive increase in global protein synthesis. These findings are consistent with the hypothesis that adipose tissue structure plays an important role in leptin expression and secretion.

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