IL-1β in health and diseases: bridging adipogenesis to systemic inflammation

Extensive research has investigated the role of IL-1β as a pivotal cytokine mediating immune-related host-defence mechanisms. It has been described that chronic exposure IL-1β, as observed in obesity, inhibits adipogenesis and contributes to systemic inflammation. In the first manuscript, our work introduces the notion that IL-1β acutely plays a physiological role in promoting adipogenesis. Through in vitro and in vivo experiments, we demonstrate that acute exposure to IL-1β, such as observed postprandially, promotes adipogenesis, particularly in early-differentiation-stage adipocyte progenitor cells. Further, we demonstrate that obesity and chronic inflammation, resulting from overnutrition, shift the physiological role of IL-1b to an inflammatory pathological process. In the second manuscript of this thesis, we conduct a comparative analysis of clinical parameters, fatty acid profiles, immune cell subsets, and inflammatory responses of peripheral blood mononuclear cells (PBMCs) obtained from both healthy individuals and those diagnosed with type-2 diabetes (T2D). We show that patients with T2D exhibit mild systemic inflammation. Surprisingly, we did not detect significant alterations in pro-inflammatory profile of PBMCs nor shifts in the immune cell population of our study participants. However, the total number of immune cells was increased in the circulation of individuals with T2D. Thus, we conclude that the observed systemic inflammation is likely due to the elevated number of circulating leukocytes rather than an elevated proinflammatory profile of these circulating cells. Furthermore, we show that pharmacological inhibition of caspase-1 and NLRP3 blunted IL-1b secretion by PBMCs. Thus, our findings suggest that inhibition of NLRP3 inflammasome components are promising therapeutic approaches for managing diabetes and its associated comorbidities.