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Thiamine (vitamin B1), which plays an important role in glucose metabolism, can prevent diabetic complications, including those in obesity. We previously found that thiamine intervention can impact metabolic abnormalities, such as progressive obesity and metabolic disorders similar to human metabolic syndrome, in polyphagia-induced Otsuka Long-Evans Tokushima Fatty (OLETF) rats. Thiamine intervention averted obesity, mainly resulting from reduction in visceral adiposity, and prevented metabolic disorders in OLETF rats. Seventy-six genes showed at least a two-fold difference in hepatic expression with thiamine treatment. Several of these genes participated in carbohydrate metabolism, lipid metabolism, vascular physiology and carcinogenesis. Thiamine has a potential to prevent obesity and metabolic disorders in OLETF rats. Although corroboration is necessary, the present findings indicate that thiamine may be beneficial in targeting composite physiological abnormalities, rather than individual component criteria, and can be used for preventive intervention. Given the detrimental effects of obesity and the safety and cost-effectiveness of thiamine, we believe that its use offers considerably more benefits than disadvantages.