3M-Brazzein, a Natural Sugar Substitute, can Suppress Metabolic Disorders, NAFLD, and Depression-like Behaviors in Diabetic Mice

The increasing consumption of sugar-sweetened beverages (SSBs) in modern society has enhanced the epidemic of obesity, metabolic disorders, and mental illnesses. Therefore, the current study investigated the potential of 3M-Brazzein as a promising natural sugar substitute. 4-weeks-old leptin receptor knockout mice (db/db) were supplied with water, 10% sucrose solution, or a 3M-Brazzein solution respectively for 16 weeks. Chronic consumption of 3M-Brazzein did not cause any degeneration of adipogenesis, insulin resistance, hepatic lipogenesis, and depression-like behaviors. However, 10% sucrose consumed mice exhibited completely different outcomes. Furthermore, the mRNA expression levels of GLUT2, SREBF-1, and PPARγ in liver were significantly increased in knockout mice supplied with the 10% sucrose solution, thereby the excessive sucrose consumption induced severe obesity, impairment of glucose homeostasis, non-alcoholic fatty liver disease (NAFLD), and major depressive disorder in them. Consequently, the present study demonstrated the positive effects of 3M-Brazzein on various health problems prevalent in the modern world, and suggests some genetic clues related to the pathogenesis of NAFLD and major depressive disorder.