The worldwide increase in degenerative diseases is in part due to modifications in the lifestyle including the diet. Epidemiological, clinical, and experimental evidence shows that soy protein may prevent lipotoxicity in non-adipose tissues during obesity. The molecular mechanism by which soy protein prevents lipotoxicity involves a reduction in the insulin/glucagon ratio, resulting in a down-regulation of lipogenic genes mediated by the transcription factor sterol regulatory element-binding protein (SREBP)-1, and up-regulation of SREBP-2 to reduce serum cholesterol. In addition, soy protein maintains the functionality of adipose tissue-liver axis to prevent hepatic steatosis during the development of obesity.