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Int J Toxicol, 29(5), 551561

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INTRODUCTION Obesity is a major public health problem around the world that is linked to severe comorbid disease conditions, physical impairment, high mortality rates, and compromised quality of life.[14] Obesity is characterized by the buildup of excessive body fat and extreme dysregulation in whole-body energy expenditure, glucose, hormone, and lipid homeostasis that typically present as adverse metabolic disorders.[4, 5] Additionally, the physiological, metabolic, and psychological changes that accompany obesity are major factors in the development of type 2 diabetes (T2D), cardiovascular disease (CVD) (e.g., coronary heart disease, dyslipidemia, hypertension),[6, 7] stroke, inflammation, non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), osteoarthritis, sleep apnea, and several obesity-linked cancers (e.g., colorectal, breast, kidney, prostate).[6, 8] Lifestyle modifications including diet and exercise may help reverse obesity and improve chronic disease biomarkers (e.g., T2D),[9] but are largely ineffective in achieving sustained weight loss and glycemic control.[10] Pharmacological treatments for obesity exist, but unfortunately most approved anti-obesity drugs have only modest efficacy and/or produce severe adverse effects (e.g., cardiovascular risks, central nervous system effects)