RESUMEN
Supplementation with the NAD+ precursor nicotinamide riboside (NR) ameliorates and prevents a broad array of metabolic and aging disorders in mice. However, little is known about the physiological role of endogenous NR metabolism. We have previously shown that NR kinase 1 (NRK1) is rate-limiting and essential for NR-induced NAD+ synthesis in hepatic cells. To understand the relevance of hepatic NR metabolism, we generated whole body and liver-specific NRK1 knockout mice. Here, we show that NRK1 deficiency leads to decreased gluconeogenic potential and impaired mitochondrial function. Upon high-fat feeding, NRK1 deficient mice develop glucose intolerance, insulin resistance and hepatosteatosis. Furthermore, they are more susceptible to diet-induced liver DNA damage, due to compromised PARP1 activity. Our results demonstrate that endogenous NR metabolism is critical to sustain hepatic NAD+ levels and hinder diet-induced metabolic damage, highlighting the relevance of NRK1 as a therapeutic target for metabolic disorders.
Asunto(s)
Dieta Alta en Grasa/efectos adversos , Hepatopatías/prevención & control , Niacinamida/análogos & derivados , Fosfotransferasas (Aceptor de Grupo Alcohol)/genética , Sustancias Protectoras/metabolismo , Sustancias Protectoras/farmacología , Animales , Glucemia , Daño del ADN , Modelos Animales de Enfermedad , Técnicas de Inactivación de Genes , Predisposición Genética a la Enfermedad/genética , Intolerancia a la Glucosa , Hepatocitos/metabolismo , Resistencia a la Insulina , Metabolismo de los Lípidos , Hígado/metabolismo , Hepatopatías/genética , Hepatopatías/patología , Masculino , Síndrome Metabólico/genética , Síndrome Metabólico/prevención & control , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , NAD/metabolismo , Niacinamida/genética , Niacinamida/metabolismo , Niacinamida/farmacología , Compuestos de PiridinioRESUMEN
The Brazilian Healthy Eating Index-Revised (BHEI-R) can be used to determine overall dietary patterns. We assessed the BHEI-R scores in children and adolescents, aged from 9 to 13 years old, and associated its component scores with biomarkers of health and dietary exposure. Three 24-h recalls were used to generate BHEI-R. Biomarkers were analyzed in plasma and red blood cells. Correlation tests, agreement, and covariance analyses were used to associate BHEI-R components with biomarkers. Data from 167 subjects were used. The strongest correlations were between fruits, vegetables and legumes with omega-6 and omega-3 fatty acids, and ß-carotene intakes. Milk and dairy correlated with plasma retinol and pyridoxine. All components rich in vegetable and animal protein sources correlated with plasma creatine. Total BHEI-R scores were positively associated with intakes of omega-6, omega-3, fiber and vitamin C, and inversely associated with energy and saturated fat intakes of individuals. Plasma ß-carotene and riboflavin biomarkers were positively associated with total BHEI-R. An inadequate food consumption pattern was captured by both biomarkers of health and dietary exposure. BHEI-R was validated for the above dietary components and can be associated with metabolomics and nutritional epidemiological data in future pediatric studies.