Adipocita e Flogosi: Ruolo di Adipochine e Vitamina D

Obesity is bound to a cronic, low-grade inflamed status of adipose tissue (AT), associated not only with a metabolic risk, but also neoplastic, leading to worse prognosis about a broad spectrum of pathologies. It was supposed a leading role for AT as regard crosstalk with immune cells and AT inflamed status. The aim of this study was to investigate the relationship between adipocytes and inflammation. From an experimental model based on 3T3-L1 cells, stimulated with lipopolysaccharide (LPS) in various times and doses, expressions of adipokines was examined, as regards both mRNA from cellular lysate, and secreted proteins in cellular medium (with ELISA). Modulations were observed with general augmented expressions of inflammatory citokines (IL-6, TNF-α, CCL3, CCL4, CXCL12), while there was a reduction in anti-inflammatory response (IL-10). The role of calcitriol (1,25[OH]2D3) was investigated in adipocyte’s physiology and pathophysiology, in relation to adipogenic and inflammatory functions. For this reasons, transcriptional and morphological effects were investigated, both of 1,25[OH]2D3 and of its parent compound colecalciferol (D3) on adipocytes differentiated from 3T3-L1, SGBS, primary cultures preadipocytes and fresh-isolated adipocytes. Also in conjunction with [Ca2+]e and LPS stimulations. Adipocytes showed enzymes for D3, such as CYP27A1 and CYP27B1. D3 treatment showed a similar antiinflammatory trend compared to 1,25[OH]2D3 one, with a reduction in IL-6, TNF-α and an increase in IL-10. As regards morphology, some changes were observed, about lipid droplets’ optical density (OD), area and diameter of adipocytes. D3 and 1,25[OH]2D3, indeed, increased adipocytes area and diameter, reducing OD. LPS showed opposite effects, while pretreatment with D3 and 1,25[OH]2D3 spared variations induced by LPS stimulation. These effects seem to be highlighted by the increase of [Ca2+]e, also in relation with LPS treatment. Using AT bioptic material, the differences in adipocytes’ morphology were studied, inflammatory status and macrophages’ infiltration among peritumoral AT (PAT), visceral AT distant from the tumor (VAT) and subcutaneous AT (SAT). Histopathological analyses revealed that PAT adipocytes were smaller then VAT and SAT adipocytes. Furthermore, the PAT was mainly infiltrated by M2-subtype macrophages, while the macrophages identified in other AT depots presented mainly M1-features. PAT also presented a higher expression of adiponectin, compared to SAT and VAT. In conclusion, these data showed the AT response capabilities to inflammation are strictly regulated. AT seems to be able to react both to inflammatory and anti-inflammatory stimulations. Therefore, AT alterations could involve pathological effects, alike cancer or metabolic syndrome. So, any possibility to interfere with these processes could be pivotal, reducing AT inflammation. Future studies may identify potential targets useful to modulate inflammation in AT.