Abstract: Adipose tissue plays a critical role in regulating metabolism and inflammation. In obesity, adipose tissue adopts a pro-inflammatory profile that contributes to metabolic diseases. Obese adipose tissue derived mesenchymal stromal cells (MSCs) significantly contribute to inflammation. Notably, adipose tissue retains an “obesogenic memory” even after weight loss, predisposing to an accelerated response to future obesogenic stimuli. MSCs are known as modulators of the immune response and secrete a range of cytokines and chemokines, influencing both local and systemic inflammation. Umbilical cord (UC) MSCs are of fetal origin but highly influenced by the intrauterine environment. These unique MSCs retain inflammatory signatures and can inform on the transgenerational impact on the differentiation and function of offspring adipocytes. These investigations are crucial to understand the intergenerational transfer of metabolic risk from the inflammatory state of the mother resulting from obesity. We have developed methods to extract UC MSCs from Wharton Jelly mechanically as described previously. We aim to extract and investigate MSCs from 10 mothers with pre pregnancy obesity compared to 10 with normal BMI ( < 25 kg/m2). This study suggests that MSCs from obese donors will exhibit an inflammatory signature resembling the donor's adipose tissue, supporting the concept of "obesogenic memory." We hypothesize that RNA, protein, and DNA analyses (RNA-seq, Western blot, ATAC-seq, single cell RNA-seq) will reveal donor-dependent differences in inflammatory (IL-6, IL-10, TNF-α) and adipogenic markers (PPARγ, Pref-1). Furthermore, multiplex cytokine assays (ELISA) are expected to demonstrate distinct cytokine secretion profiles in media collected at Days 0 and 21 of differentiation. By exploring these results, this study aims to provide novel insights into obesity-associated inflammation, the intergenerational impact of maternal obesity, and the development of therapeutic strategies to treat metabolic disorders.
