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Diet-induced obesity promotes a myeloma-like condition in vivo

Leukemia volume 29, pages 507–510 (2015)Cite this article

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Multiple myeloma remains a fatal haematological malignancy associated with clonal plasma cell expansion within the bone marrow, osteolytic bone disease, anaemia and renal failure. In almost all cases, myeloma is preceded by the nonmalignant plasma cell disorder monoclonal gammopathy of undetermined significance (MGUS), characterized by an increase in monoclonal immunoglobulin secretion, <10% plasma cells within the bone marrow and a lack of lytic bone lesions. The mechanisms underlying the pathogenesis of MGUS and progression to myeloma are complex with a major role attributed to the host microenvironment. A loss of host-derived adiponectin is known to promote myeloma development in vivo, both in murine models and in patients with MGUS.1 Adiponectin is inversely linked to obesity, with increasing epidemiological evidence supporting an association between obesity and MGUS or myeloma.2, 3, 4, 5, 6, 7 In the present study, we have combined a well-characterized murine model of myeloma with diet-induced obesity and a genetic model of obesity to determine the effect of increased obesity on myeloma development in vivo.

To determine the effect of withdrawal of the high-fat diet, in a separate experiment C57BL6 mice were placed on the high-fat diet or control. Two weeks post-tumour inoculation, following detection of an increase in serum paraprotein, mice were either removed from the high-fat diet and returned to the control diet, or remained on the high-fat diet for the duration of the experiment (Supplementary Figure 2). Five weeks post-inoculation, all mice were sacrificed and tumour burden assessed. As before, C57BL6 mice inoculated with 5TGM1 cells and continuously fed a high-fat diet developed features of myeloma, whereas tumour-inoculated mice that were fed a control diet did not develop significant pathology (Figure 1f). Removal of mice from the high-fat diet resulted in a reduction in tumour burden, but no change in trabecular bone volume, with the myeloma-induced trabecular bone defect suggestive of a delayed response to tumour regression (Figures 1f and g). Combined, these in vivo data show that continuous diet-induced obesity promotes the establishment of an MGUS-like condition with associated bone loss, and that tumour burden is reduced upon removal of the diet, raising the possibility for effective dietary intervention strategies.

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Acknowledgements

This work was supported by the National Cancer Institute through R01-CA137116, an American Society of Bone and Mineral Research Career Establishment Award and a Marie Curie Career Integration Grant within the 7th European Community Framework Programme.

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  1. S T Lwin and S W Z Olechnowicz: These authors contributed equally to this work.

Authors and Affiliations

  1. Nuffield Department of Surgical Sciences, University of Oxford, Oxford, UK

    S T Lwin, S W Z Olechnowicz & C M Edwards

  2. Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, Botnar Research Centre, University of Oxford, Oxford, UK

    S T Lwin & C M Edwards

  3. Vanderbilt Center for Bone Biology, Vanderbilt University, Nashville, TN, USA

    S T Lwin, J A Fowler & C M Edwards

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  1. S T Lwin
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Correspondence to C M Edwards.

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Lwin, S., Olechnowicz, S., Fowler, J. et al. Diet-induced obesity promotes a myeloma-like condition in vivo. Leukemia 29, 507–510 (2015). https://doi.org/10.1038/leu.2014.295

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