158 Appendix ENGLISH SUMMARY Chronic obstructive pulmonary disease (COPD) and diabetes are widespread chronic diseases worldwide. COPD, characterized by persistent airflow limitation, significantly impacts lung function, causing respiratory symptoms and contributing to comorbidities like cardiovascular disease, affecting patients’ quality of life. Diabetes, encompassing type 1 and type 2 variations, results in high blood sugar levels due to insulin imbalance, leading to various complications such as retinopathy and nephropathy. Both COPD and diabetes are characterized by chronic inflammation, marked, among many features, by the presence of pro-inflammatory cytokines affecting all tissues. Macrophages, cells of the immune system, play a pivotal role in chronic inflammation and in the intricate relationship between immune and metabolic processes in tissue. Chronic inflammation influences changes in energy metabolism also through lysine acetylation in proteins, altering gene expression and impacting cellular energy processes like glycolysis and fatty acid oxidation. This connection highlights the interplay between immune responses and metabolic pathways in these chronic conditions, emphasizing the significance of understanding their complex interactions for developing targeted therapies. This thesis aimed to deepen our understanding of macrophages within chronic inflammation, focusing on their diverse phenotypes and metabolic nuances across various tissue niches. In Chapter 2 the focus is on the involvement of macrophages in obesity and type 2 diabetes mellitus. It describes distinct phenotypes associated with these conditions and sheds light on variations in cellular metabolite levels, revealing how microenvironments influence macrophage behavior. This chapter also illustrated the most common ways to characterize macrophages, with particular attention paid to their metabolism. Subsequently, the investigation delved into the effects of KDAC inhibitors (KDACis) on primary murine alveolar-like macrophages activated by lipopolysaccharide (LPS), described in Chapter 3. While minimal metabolic changes were observed between conditions, the study revealed that when macrophages were treated with KDACis, a reduction in inflammatory mediators and an enhancement in proteins related to ubiquitination was observed, potentially offering new therapeutic avenues for COPD. In Chapter 4 we explored how collagen morphology influences macrophage behavior and metabolism. We uncovered changes in glycolysis-related protein
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