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195320 https://hdl.handle.net/2286/R.2.N.195320 http://rightsstatements.org/vocab/InC/1.0/ All Rights Reserved 2024 64 pages Masters Thesis Academic theses Text eng Dahal, Merina Wang, Shu Kim, Min-Hyun Gu, Haiwei Roberts, Joseph Arizona State University Partial requirement for: M.S., Arizona State University, 2024 Field of study: Nutrition Obesity has become a significant health problem due to its association with various chronic diseases and metabolic disorders. Browning of white adipose tissues (WAT) has emerged as a potential therapeutic approach for the treatment of obesity. The purpose of this study was to study and compare the browning WAT and anti-obesity effects of forskolin, rosiglitazone, mirabegron, and CL316,243 in high-fat diet (HFD)-induced obese mice. Seven-week-old C57BL/6J mice were fed a HFD (45% kcal from fat) to induce obesity. After 4 weeks, 25 mice were randomly assigned to one of the five following groups: control (tween 80), forskolin, rosiglitazone, mirabegron and CL316,243. All the treatments were locally injected into the inguinal WAT (IWAT) of mice twice a week for 5 weeks at the dose of 15 mg/kg body weight. At the end of 5 weeks, mice were euthanized, and the blood and tissues were collected for analysis. No significant difference was observed between the body weight, fat mass, body fat percentage, lean mass, and body lean percentage of the mice between the groups after 5 weeks of treatment. In terms of glucose metabolism, fasting serum glucose levels were found to be significantly lower (p<0.0001) in forskolin-treated mice at the end of treatment, but the CL316,243-treated mice had the lowest area-under the curve during the glucose tolerance test (p=0.0075). The CL316,243 group showed significantly higher gene expression of browning marker uncoupling protein-1 (UCP1) (p<0.0001) in the IWAT along with a higher expression of lipid metabolism regulating genes like acetyl Co-A carboxylase 1 (ACC1), adipose triglyceride lipase (ATGL) and hormone sensitive lipase (HSL) in the IWAT. CL316,243 treatment also increased the serum levels of adiponectin compared to the control (p<0.0001) and other treatments. The expression of F4/80 gene was significantly higher in mirabegron-treated mice. The forskolin group showed some signs of renal toxicity indicated by their high blood urea nitrogen (p=0.0008) and phosphorus levels (p<0.0001) in the serum. Similarly, rosiglitazone group had high liver weight (p=0.0022) and serum alkaline phosphatase levels (p=0.0014), suggesting its potential hepatotoxic effects. These findings suggest that CL316,243 might have a higher browning and anti-obesity effects compared to other treatments whereas forskolin and rosiglitazone treatments might have renal and hepatotoxic effects respectively. Nutrition Nutrition Comparison of Browning and Anti-Obesity Effects of Local Administration of Forskolin, Rosiglitazone, Mirabegron and CL316,243 in Obese Mice