Using multi-omics to investigate the impact of fine particulate matter on diet-induced liver disorders

For years, metabolic diseases such as obesity, chronic liver disorders, and diabetes have been progressively growing in prevalence. The rapid increase in fat and sugar consumption per capita has been linked to a significant rise in the prevalence of these disorders. Non-alcoholic fatty liver disease, or NAFLD, is the most frequent form of chronic liver disease, it can cause a number of other problems. Fine particulate matter (also known as PM2.5) is the most significant environmental risk factor for disease and fatality worldwide. PM2.5 levels have been associated with the incidence and prevalence of a range of non-communicable disorders, such as NAFLD, in epidemiological and experimental studies. The molecular mechanisms underlying PM2.5-induced toxicity in the development of NAFLD, however, remain unknown. The proposed study will apply a mouse model and a multi-omics analysis using mass spectrometry (MS) to investigate the essential molecular components involved in the aggravation of diet-induced NAFLD caused by PM2.5. Normal mice will be separated into four groups at random. Half of the mice (two groups) will be fed standard chow and the other half will be fed a diet higher in fat, sugar, and cholesterol. Meanwhile, in a real-world exposure system, one group from each diet plan will be exposed to ambient PM2.5. Mice from each group will be sacrificed every four weeks to track the development and progression of NAFLD. The molecular changes in the blood, liver and other tissues caused by the energy- dense diet and/or PM2.5 exposure will then be investigated using proteomics, phosphoproteomics, metabolomics, and lipidomics. The machine learning approach will be modified to detect organ covariation. A comparison of the different groups will highlight the potential pathways and key proteins involved in the development of NAFLD. Using molecular genetics, we will then validate the roles and activities of their corresponding proteins in human cells. This study is expected to show that PM2.5 has an inverse effect on the development of NAFLD. The findings are expected to provide information on the relationship between high sugar and fat consumption and the development of NAFLD, as well as evaluate the toxicological effects of PM2.5, providing a mechanistic understanding of the role of PM2.5 in diet-induced liver disorders.