Semaphorin 3C-a novel adipokine modulating human adipose tissue plasticity in weight change
N. Mejhert1, F. Wilfling2, J. Galitsky3, C. Kolditz3, N. Viguerie3, E. Näslund4, P. Trayhurn5, I. Dahlman1, D. Langin3, A. Bouloumié3 & M. Rydén1
Context: Alterations in white adipose tissue (WAT) function, including changes in extracellular matrix (ECM) composition, play an important role in conditions of both weight gain and loss.
Objective: We set out to identify novel genes regulated by obesity and cancer cachexia in human scWAT with potential roles for adipocyte function and/or tissue remodelling.
Design Candidate genes were selected by overlapping previously published global gene expression profiles in human WAT (n=X) with functional RNAi screens assessing lipid droplet morphology in Drosophila S2-cells. In vitro experiments were performed in primary cultures of human preadipocytes/adipocytes.
Results: 33 genes regulated by obesity/cachexia had orthologues in Drosophila and of these two affected lipid droplet morphology in the RNAi screen. One of the two, semaphorin 3C (SEMA3C), encodes a secreted factor not previously studied in human adipocytes. SEMA3C mRNA expression was increased in obesity and decreased in cancer cachexia. In addition, SEMA3C was predominantly expressed/secreted by mature adipocytes. Incubating human adipocytes with recombinant SEMA3C had no effect on differentiation, lipolysis, glucose transport or the expression of lipid oxidation genes which could be explained by the significant down-regulation of the SEMA3C receptors/co-receptors during adipocyte differentiation. In contrast, incubation of human pre-adipocytes with SEMA3C increased the production of the ECM-related factors fibronectin 1 and connective tissue growth factor in a concentration-dependent manner without any effects on differentiation.
Conclusions: SEMA3C is a novel adipokine altered by weight changes that regulates the expression of ECM genes in preadipocytes. SEMA3C may therefore play a role in tissue plasticity and remodelling.
Declaration of interest: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.
Funding: This work was supported, however funding details are unavailable.