High Fat Diet Rapidly Suppresses B Lymphopoiesis by Disrupting the Supportive Capacity of the Bone Marrow Niche

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Abstract

The bone marrow (BM) niche is the primary site of hematopoiesis, and cues from this microenvironment are critical to maintain hematopoiesis. Obesity increases lifetime susceptibility to a host of chronic diseases, and has been linked to defective leukogenesis. The pressures obesity exerts on hematopoietic tissues led us to study the effects of a high fat diet (HFD: 60% Kcal from fat) on B cell development in BM. Seven week old male C57Bl/6J mice were fed either a high fat (HFD) or regular chow (RD) diet for periods of 2 days, 1 week and 6 weeks. B-cell populations (B220+) were reduced following 1W and 6W of HFD as were markers of B-cell development. Importantly, the secreted B-cell differentiation factor IL-7 was reduced after only 2D demonstrating how susceptible the BM niche, and the cells which rely on it, are to diet. Interestingly, the reversal of obesity accomplished through a change in diet is not successful at fully reversing defects in leukocyte populations. As a countermeasure to obesity’s influence on the BM niche, we also investigated the influence of whole body Low Intensity Vibrations (LIV), which are known to interact with several key components of the niche including mesenchymal stem cells and osteoblasts. These signals led to modest improvements in the quality of the BM niche, notably by increasing hematopoietic progenitors and the expression of IL-7. These improvements translated into recovery of circulating B-cell populations in a long term study, in which LIV also benefited bone architecture and fat mass relative to HFD animals. These data demonstrated the acute susceptibility of BM hematopoiesis to obesity and changes in diet. While obesity represents a strong negative influence on the BM niche, subtle mechanical signals in the form of LIV show potential as an adjuvant for BM and systemic health. These signals improved regulatory signaling in the niche and set in motion recovery processes which led, over a long term exposure, to restoration of leukocyte populations. In addition LIV improved parameters of liver and skeletal health demonstrating the systemic influence of mechanical stimulation.

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