Refeeding syndrome (RFS) refers to the metabolic and clinical changes that occur with rapid or excessive administration of feeding, whether orally, enterally or parenterally, following a period of relative or absolute starvation (1). RFS is characterized by fatal complications such as heart failure, arrhythmia, respiratory failure and cardiac arrest (2) ; thus, the prevention of RFS is vital. In general, individuals with marasmus or kwashiorkor are at risk for RFS, particularly in cases of greater than 10% weight loss over a couple of months. Furthermore, patients are at risk after prolonged fasting, massive weight loss in chronic alcoholism, prolonged intravenous fluid repletion and anorexia nervosa (3, 4). Currently, this syndrome is common among elderly people with poor nutritional intake due to alcoholism or dementia in the clinical practice.Hypophosphatemia is the hallmark of RFS and is key to its prevention and treatment (5). Further, it is reported to be associated with increased mortality in critically ill patients (6, 7). The mechanism of refeeding hypophosphatemia can be described by the following hypothesis. With the reintroduction of carbohydrates to malnutrition patients, anabolism begins immediately and the body shifts to carbohydrate metabolism from fat catabolism. The increased glucose load, with a corresponding increase in the release of insulin, leads to cellular uptake of glucose, potassium (K), magnesium (Mg), and phosphate (Pi). This shift of electrolytes into the cell causes hypokalemia, hypomagnesemia, and hypophosphatemia (8,9). Patients consistently present with hypophosphatemia, although the other symptoms are not always detected. However, the molecular mechanisms of hypophosphatemia and RFS require elucidation.RFS is more likely to occur after parenteral or enteral feeding (10). In a study of patients that received total parenteral nutrition (TPN), the incidence of hypophosphatemia ranged from 30 -38% when Pi was provided in the solution, to 100% when TPN without Pi was administered (11). The RFS guideline of the National Institute for Health and Clinical Excellence (NICE) in England and Wales recommends that nutritional repletion of energy should be started slowly, and Pi supplementation should be given unlessblood levels are high before refeeding (12). Pi supplementation was reported to reduce the incidence of hypophosphatemia in hospitalized patients receiving TPN (13). Thus, Pi has an important role in RFS.Guidelines on the prevention and treatment of this syndrome are available ; however, cases continue to be seen clinically. One reason why the mechanism of RFS is unknown is the lack of an appropriate animal model. To our knowledge, there are no reports of animal models with hypophosphatemia, making investigation of RFS challenging. Thus, the development of an animal model is vital for the detailed evaluation of RFS as well as clarification of its molecular mechanism. In this study, as a first step toward revealing the mechanism of RFS, we attempted to develop an RFS animal model ...