Intervention with citrus flavonoids reverses obesity and improves metabolic syndrome and atherosclerosis in obese Ldlr−/− mice

Abstract

diabetes, cardiovascular disease, and hepatic steatosis, which collectively represent one of the leading causes of adult morbidity and mortality worldwide (1-3). This suggests that restoration of functional energy homeostasis is critical for therapeutic intervention. Despite efforts to develop anti-obesity medications that curtail symptoms of metabolic dysfunction, drugs that have reached the market have limited efficacy for obesity (5-8%) and many have been withdrawn for negative side effects (3-6). Currently available therapeutics predominantly work by either reducing caloric intake or blocking food absorption (3). Additionally, patients often regain lost weight. The treatment strategy with the most robust and lasting improvements is gastric bypass surgery, which has shown up to 25% weight loss at 12 years together with a 51% remission rate for type 2 diabetes (7). Presently, gastric bypass surgery as an intervention for obesity and metabolic syndrome is limited to patients with a BMI 35 kg/m 2 (8), excluding patients with moderate obesity, although these patients often present with increased metabolic dysfunction and cardiovascular risk (9, 10). Therefore, there is urgent need for safe and effective medical therapies for obesity and its associated complications, including the metabolic syndrome and cardiovascular disease.