Key words: inflammation, non-alcoholic fatty liver disease, lysosomes, small-molecule inhibitors

"Small molecules, big consequences: Novel therapeutic approaches for treating chronic inflammatory diseases"

Obesity has become a global epidemic due to increase in sedentary lifestyle and calorie intake. In addition to increased BMI, obese patients display a persistent, low-grade inflammatory response known as "metabolic inflammation." This metabolic inflammation is linked to several diseases, including heart diseases, non-alcoholic fatty liver disease (NAFLD), type 2 diabetes as well as inflammatory bowel disease (IBD). The focus of this thesis is to understand the mechanism underlying these metabolic inflammatory processes with a goal to identify novel and safe therapeutic approaches. One of the main mechanisms responsible for this metabolic inflammatory response is the disturbed cholesterol metabolism in macrophages, which are immune cells that kill and clear pathogens. This thesis tested small-molecule compounds that help improve cholesterol metabolism in macrophages and thereby reduce inflammation using several mice models. In addition, this thesis also discussed the importance of non-pharmacological stress-reduction strategies in reducing inflammation and improving quality of life in these patients.

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