Establishment of Model Mice to Evaluate Low Niacin Nutritional Status.

Abstract

Niacin is involved in many biological reactions relating energy metabolism, redox reactions, DNA repair and longevity, and low NAD levels with aging and feeding high fat diets develop and progress age-related diseases. Although recent findings suggest the requirement of niacin insufficient animal model to further study, appropriate animal models have not been established yet because niacin is biosynthesized from tryptophan via tryptophan-nicotinamide pathway. To establish model mice to evaluate niacin nutritional status, we used kynurenine 3-monooxygenase knock out (KMO^-/-) mice which lack NAD biosynthesis pathway from tryptophan. To determine the niacin requirement and assess niacin nutritional markers, 4 wk old KMO^-/- mice were fed 2-30 mg/kg nicotinic acid containing diets for 28 d. More than 4 mg/kg but not less than 3 mg/kg nicotinic acid containing diets induced maximum growth, and niacin nutritional markers in the blood, liver and urine increased with increase of dietary nicotinic acid. These results showed that several niacin nutritional markers reflect niacin nutritional status, niacin nutritional status can be controlled by dietary nicotinic acid, and niacin requirement for maximum growth is 4 mg/kg nicotinic acid diets in the KMO^-/- mice. This animal model useful to investigate pathophysiology and mechanism of niacin deficiency, clarify the relationships between niacin nutritional status and age-related and lifestyle diseases, and evaluate factors affecting niacin nutritional status.