Regulation of Adipogenesis by Lymphatic Fluid Stasis Part I

Regulation of Adipogenesis by Lymphatic Fluid Stasis Part I: Adipogenesis, Fibrosis, and Inflammation

Zampell JC, Aschen S, Weitman ES, Yan A, Elhadad S, De Brot Andrade M, Mehrara BJ; 2012

Synopsis: This study tested the effect of slowing or stopping the flow of lymph fluid on fatty tissue formation and inflammation, and how these changes regulate the expression of fat differentiation genes.

Abstract: BACKGROUND: Although fat deposition is a defining clinical characteristic of lymphedema, the cellular mechanisms that regulate this response remain unknown. The goals of this two-part study were to determine the effect of lymphatic fluid stasis on adipogenesis and inflammation (part 1) and how these changes regulate the temporal and spatial expression of fat differentiation genes (part 2).

METHODS: Adult female mice underwent tail lymphatic ablation and were sacrificed 6 weeks after surgery (n=20). Fat deposition, fibrosis, and inflammation were then analyzed in the regions of the tail exposed to lymphatic fluid stasis as compared with normal lymphatic flow.

RESULTS: Lymphatic fluid stasis in the tail resulted in significant subcutaneous fat deposition with a 2-fold increase in fat thickness (p<0.01). In addition, lymphatic stasis was associated with subcutaneous fat fibrosis and collagen deposition. Adipogenesis in response to lymphatic fluid stasis was associated with a marked mononuclear cell inflammatory response (5-fold increase in CD45+ cells; p<0.001). In addition, we noted a significant increase in the number of monocytes/ macrophages as identified by F4/80 immunohistochemistry (p<0.001).

CONCLUSIONS: The mouse-tail model has pathological findings that are similar to clinical lymphedema including fat deposition, fibrosis, and inflammation. Adipogenesis in response to lymphatic fluid stasis closely resembles this process in obesity. This model therefore provides an excellent means to study the molecular mechanisms that regulate the pathophysiology of lymphedema.

APA Citation: Zampell, J., Aschen, S., Weitman, E., Yan, A., Elhadad, S., De Brot, M., & Mehrara, B. (2012). Regulation of Adipogenesis by Lymphatic Fluid Stasis. Plastic And Reconstructive Surgery, 129(4), 825-834. http://dx.doi.org/10.1097/prs.0b013e3182450b2d

AMA Citation: Zampell J, Aschen S, Weitman E et al. Regulation of Adipogenesis by Lymphatic Fluid Stasis. Plastic and Reconstructive Surgery. 2012;129(4):825-834. doi:10.1097/prs.0b013e3182450b2d.