Obesity, diabetes, cardiovascular and neurodegenerative diseases (so-called civilization diseases) – are the world’s leading causes of morbidity and mortality and are responsible for60% of all deaths. It appears that obesity, type 2 diabetes (T2DM) and neurodegeneration have a common etiopathogenesis involving subclinical inflammation and insulin resistance. In the proposed project, we will explore the efficacy of new lipidized analogs of anorexigenic prolactinreleasing peptide as a complex therapy that simultaneously affects obesity, T2DM and neurodegeneration in mouse and rat models. In parallel, in these models peripheral biomarkers or panel of biomarkers of neurodegeneration development and long-term monitoring of its progression and treatment will be identified using of a comprehensive methodological portfolio including metabolomics in urine and plasma and advanced mass spectrometry imaging methods. Results of this project could help to find a common denominator of these major civilization diseases and open new possibilities for their comprehensive treatment.