The Anti-obese Effect And Action Mode Of N-stearoyltryosine Dipotassium

As a common chronic endocrine metabolic disease, the incidence of obesity showed a rising trend these years and has become a global health problem. Obesity could not only increase the incidence and death rate of hypertension, coronary heart disease and type 2diebetes, but also induce respiratory complications, arthritis and psychiatric disorders.Thus, the study on the pathogenesis of obesity and the development of the anti-obese drugs which possess both safety and effectiveness have become a topical issue of the world.As an analogue of endocannabinoids, N-stearoyltyrosine(NST) inhibits the activity of fatty acid amide hydrolase(FAAH) and prolongs the action of endocannabinoids, which finally protects the neurons from the insults induced by oxygen glucose deprivation(OGD). During the preclinical study, we found that NST reduced the body weight of KM mice. To increase the solubility of NST, we converted it into its dipotassium and carried out the research of the anti-obese effect of NST-2K.In this study, we first optimized the preparation method and obtained N-stearoyltyrosine dipotassium(NST-2K) with high yield and purity for animal experiment. Then, diet-induced obese(DIO) mice model was applied for the research of the anti-obese effect of NST-2K. The DIO mice were induced from male C57BL/6 mice by feeding high-fat diet for 11-weeks and treated orally with NST-2K for other 4 weeks.The treatments of DIO mice with 60 mg/kg/day or 100 mg/kg/day NST-2K suppressed the body weight gain, decreased both visceral fat weight and adipocyte size without influence on food intake. To evaluate the effect of NST-2K on lipid and carbohydrate metabolism,several key molecules in the plasma, liver, duodenum mucosa and adipose tissue were analyzed. NST-2K ameliorated the low-grade inflammation in liver, inhibited pancreatic lipase activity in duodenum mucosa, activated β-oxidation system and reduced lipogenesis,thus suppressed lipid accumulation in the liver, reduced adipocyte size and improved lipid and carbohydrate metabolism.Overall, without influence on food intake, NST-2K ameliorated high-fat diet-induced obesity via(1) suppressing liver inflammation,(2) inhibiting dietary fat absorption, and(3)promoting lipolysis and reducing lipogenesis.