Chronic Endurance Exercise Impairs Niacin Nutritional Status in Mice.

Niacin is a cofactor in many biological reactions related to energy metabolism, redox reactions, DNA repair and longevity. Although it has been considered that increasing energy expenditure increases NAD consumption, little study has directly demonstrated the effect of exercise on niacin nutritional status. We have recently established the niacin insufficient model mice using kynurenine 3-monooxygenase knock out (KMO-/-) mice with niacin-limited diet, which lack the de novo NAD synthesis pathway from tryptophan. To evaluate the effects of chronic endurance exercise on niacin nutritional status, 4 wk old KMO-/- mice were fed 4 or 30 mg/kg nicotinic acid containing diets, and forced to swim in a running water pool every other day for 35 d. The swim-exercised mice fed 4 mg/kg nicotinic acid diet showed lower body weight gain and niacin nutritional markers such as liver and blood NAD, and urine nicotinamide metabolites than the sedentary mice. These animals did not show any difference in the NAD synthesis, NAD salvage and nicotinamide catabolic pathways. Chronic endurance exercise failed to affect any indices in the mice fed the 30 mg/kg nicotinic acid diet. When the diet was exchanged the 4 mg/kg for 30 mg/kg nicotinic acid diet to the mice showed chronic endurance exercise-induced growth retardation, their body weight rapidly increased. These results show that chronic endurance exercise impairs niacin nutritional status in the niacin insufficient mice, and enough niacin intake can prevent this impairment. Our findings also suggest that chronic endurance exercise increases niacin requirement by increase of NAD consumption.

Chronic Ethanol Intake Impairs Niacin Nutritional Status in Mice.

Niacin is involved in many biological reactions relating energy metabolism, redox reactions, DNA repair and longevity. Since niacin deficiency has been reported in alcoholic patients, and niacin coenzyme NAD is used as substrate to dehydrogenate ethanol in the liver, ethanol consumption can be a factor to impair niacin nutritional status. We have recently established the niacin insufficient model mice using kynurenine 3-monooxygenase knock out (KMO-/-) mice with niacin-limited diet, which lack the de novo NAD synthesis pathway from tryptophan. To evaluate the effects of chronic ethanol intake on niacin nutritional status, 4 wk old KMO-/- mice were fed 4 or 30 mg/kg nicotinic acid containing diets with or without 15% ethanol for 35 d. The mice fed 4 mg/kg nicotinic acid diet with ethanol showed lower body weight gain and niacin nutritional markers such as liver and blood NAD, and urine nicotinamide metabolites than the mice without ethanol. These animals did not show any difference in the NAD synthesis, NAD salvage and nicotinamide catabolic pathways. Chronic ethanol intake failed to affect any indices in the mice fed the 30 mg/kg nicotinic acid diet. When the diet was exchanged the 4 mg/kg for 30 mg/kg nicotinic acid diet to the mice showed chronic ethanol-induced growth retardation, their body weight rapidly increased. These results show that chronic ethanol intake impairs niacin nutritional status in the niacin insufficient mice, and enough niacin intake can prevent this impairment. Our findings also suggest that chronic ethanol intake increases niacin requirement by increase of NAD consumption.

Establishment of Model Mice to Evaluate Low Niacin Nutritional Status.

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.