The Effect of Weight Cycling on Myelopoiesis

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Abstract Inflammation is a hallmark of obesity and is associated with many complications, with myeloid cells being major culprits. Weight loss improves obesity-related comorbidities, however, subsequent weight regain, known as weight cycling (WC), has been linked to worsening of obesity-related diseases. Therefore, it is critical to understand how WC impacts inflammation. We hypothesize that mice undergoing WC will have greater myeloid cell production with heightened inflammatory capacity. To test this hypothesis, we characterized immune cell populations in bone marrow (BM) and blood using multi-parametric flow cytometry in mice undergoing acute and long-term WC compared to non-WC mice. Our results indicate WC increases the frequency of inflammatory Ly6Chi monocytes and lowers pro-resolving Ly6Clo monocytes in the BM. Additionally, WC increases circulating monocytes. The increase in monocytes are coupled with expansion of their bone marrow progenitors, suggesting that WC heightens myelopoiesis. We will further examine inflammatory capacity by stimulating bone marrow derived macrophages with lipopolysaccharide and measuring cytokine secretion. Furthermore, hematopoietic progenitor differentiation will be tested through colony forming assays. Combined RNA/ATAC-seq will be used to understand the transcriptomic and epigenetic changes occurring in progenitors with WC. This study will provide novel insight into how WC worsens disease, and the basic mechanisms regulating myelopoiesis.

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