Metabolism disrupting effects in human pre-adipocytes: Influence of donor sex and body composition

Abstract

There is growing attention on the global, worsening rates of metabolic disorders, including obesity. Numerous attempted interventions have provided only modest effects, with current rates of obesity in the United States remaining high (e.g., 42.4 % of adults and 8.9 % of infants and toddlers). Metabolism-disrupting chemicals (MDCs) are one proposed causal factor and are chemicals that can disrupt adipocyte development and differentiation in vitro and/or metabolism in vivo (e.g., increased weight, adipose). High costs prohibit comprehensive rodent screening for MDCs, necessitating the use of in vitro models to better screen and prioritize chemicals for higher-order testing. This study aimed to evaluate human adipose-derived pre-adipocytes as a potential model for determining MDCs, focusing on donor sex and body composition impacts on adipogenesis. Adipogenesis assays were performed on male and female human subcutaneous pre-adipocytes isolated from lean and obese donors. The response of each donor cell line to hormones and chemicals known to promote adipogenesis was examined, evaluating both sex and body composition impacts on triglyceride accumulation and pre-adipocyte proliferation. Results showed considerable variability between and within donor groups, complicating the findings of MDCs' consistent effects. While human pre-adipocyte models appear to offer a closer mimic of real-life responses, a careful assessment of variability is needed. Despite challenges, this model provides valuable insights into how MDCs impact individuals variably based on sex, body composition, and genetic makeup.