RESUMEN
Tissue-specific deficiency of nicotinamide phosphoribosyl transferase (NAMPT), the rate-limiting enzyme of the nicotinamide adenine dinucleotide (NAD+)-salvage pathway, causes a decrease of NAD+ in the tissue, resulting in functional abnormalities. The NAD+-salvage pathway is drastically activated in the mammary gland during lactation, but the significance of this has not been established. To investigate the impact of NAD+ perturbation in the mammary gland, we generated two new lines of mammary gland epithelial-cell-specific Nampt-knockout mice (MGKO). LC-MS/MS analyses confirmed that the levels of NAD+ and its precursor nicotinamide mononucleotide (NMN) were significantly increased in lactating mammary glands. We found that murine milk contained a remarkably high level of NMN. MGKO exhibited a significant decrease in tissue NAD+ and milk NMN levels in the mammary gland during lactation periods. Despite the decline in NAD+ levels, the mammary glands of MGKO appeared to develop normally. Transcriptome analysis revealed that the gene profiles of MGKO were indistinguishable from those of their wild-type counterparts, except for Nampt. Although the NMN levels in milk from MGKO were decreased, the metabolomic profile of milk was otherwise unaltered. The mammary gland also contains adipocytes, but adipocyte-specific deficiency of Nampt did not affect mammary gland NAD+ metabolism or mammary gland development. These results demonstrate that the NAD+ -salvage pathway is activated in mammary epithelial cells during lactation and suggest that this activation is required for production of milk NMN rather than mammary gland development. Our MGKO mice could be a suitable model for exploring the potential roles of NMN in milk.
Asunto(s)
Células Epiteliales , Lactancia , Glándulas Mamarias Animales , Ratones Noqueados , Leche , Mononucleótido de Nicotinamida , Nicotinamida Fosforribosiltransferasa , Animales , Nicotinamida Fosforribosiltransferasa/metabolismo , Nicotinamida Fosforribosiltransferasa/genética , Mononucleótido de Nicotinamida/metabolismo , Glándulas Mamarias Animales/metabolismo , Femenino , Células Epiteliales/metabolismo , Leche/metabolismo , Ratones , Lactancia/metabolismo , Citocinas/metabolismo , NAD/metabolismo , Ratones Endogámicos C57BLRESUMEN
This study introduces the Meiji Nutritional Profiling System (Meiji NPS), which was specifically designed to respond to age-related shifts in nutrient requirements among Japanese adults (<65 years old) and older adults (≥65 years old). Japan has one of the most aged societies in the world. The health issues of interest are malnutrition and lifestyle-related diseases among adults and frailty among older adults. Two versions of the NPS were developed based on nutrients to encourage (protein, dietary fibers, calcium, iron, and vitamin D), food groups to encourage (fruits, vegetables, nuts, legumes, and dairy), and nutrients to limit (energy, saturated fatty acids, sugars, and salt equivalents). The Meiji NPS for older adults did not include iron or saturated fatty acids. The algorithms were based on the Nutrient-Rich Foods Index (NRF). The convergent validity between the Meiji NPS and the existing NPSs for the same foods was confirmed using Spearman's correlation coefficients (NRF: r = 0.67 for adults and r = 0.60 for older adults; Health Star Rating: r = 0.64 for adults and r = 0.61 for older adults). The Meiji NPS may be useful for nutritional evaluation and reformulation of food products, tailored to adults and older adults to ameliorate health issues in Japan.
Asunto(s)
Dieta , Verduras , Japón , Hierro , Ácidos GrasosRESUMEN
BACKGROUND: Humans vary in their sensitivity to stressful and supportive environments and experiences. Such individual differences in environmental sensitivity are associated with mechanisms of stress-related psychiatric symptoms. In recent years, researchers have focused on bidirectional interactions in the brain-gut-microbiota axis as a neurophysiological pathway contributing to the mechanisms of stress-related psychiatric symptoms, and evidence is rapidly accumulating. METHODS: Data on environmental sensitivity, gut microbiota, gut permeability (lipopolysaccharide-binding protein; LBP) and inflammation (C-reactive protein; CRP) were collected from 90 adults (50 % female; Mage = 42.1; SDage = 10.0). Environmental sensitivity was measured using a self-report questionnaire. Study participants' feces were analyzed, and observed operational taxonomic units for richness, Shannon's index for evenness, and phylogenetic diversity for biodiversity were evaluated as indicators of gut microbiota. In addition, participants' serum was analyzed for CRP and LBP. We investigated whether the interaction between environmental sensitivity and gut microbiota is associated with biomarkers of inflammation and gut permeability. RESULTS: The interaction between environmental sensitivity and gut microbiota (excluding the Shannon's index) explained the levels of these biomarkers. Individuals with high environmental sensitivity displayed higher levels of CRP and LBP, when the richness and diversity of the gut microbiota was low. However, even highly susceptible individuals had lower levels of CRP and LBP, when the richness and diversity of the gut microbiota was high. CONCLUSIONS: Our study indicates that high environmental sensitivity can be a risk factor for inflammation and gut permeability, when the gut microbiota diversity is low, suggesting a brain-gut-microbiota axis interaction.
Asunto(s)
Microbioma Gastrointestinal , Adulto , Humanos , Femenino , Niño , Masculino , Filogenia , Biomarcadores , Proteína C-Reactiva/metabolismo , InflamaciónRESUMEN
(1) Background: Breast milk is the only source of nutrition for breastfed infants, but few studies have examined the relationship between breast milk micronutrients and infant neurodevelopmental outcome in exclusively breastfed infants. The aim of this study was to characterize the association between nicotinamide adenine dinucleotide (NAD)-related compounds in the breast milk of Japanese subjects and infant neurodevelopmental outcome. (2) Methods: A total of 150 mother-child pairs were randomly selected from the three-generation cohort of the Tohoku Medical Megabank in Japan. Infants were exclusively breastfed for up to 6 months. Breast milk was collected at 1 month postpartum, and the quantity of NAD-related substances in the breast milk was quantified. The mothers also completed developmental questionnaires at 6, 12, and 24 months. The relationship between the concentration of NAD-related substances in breast milk and developmental indicators was evaluated via ordinal logistic regression analysis. (3) Results: Nicotinamide mononucleotide (NMN) was quantified as the major NAD precursor in breast milk. The median amount of NMN in the breast milk was 9.2 µM. The NMN concentration in breast milk was the only NAD-related substance in breast milk that showed a significant positive correlation with neurodevelopmental outcome in infants at 24 months. (4) Conclusions: The results suggest that NMN in human milk may be an important nutrient for early childhood development.
Asunto(s)
Leche Humana , Mononucleótido de Nicotinamida , Preescolar , Femenino , Lactante , Humanos , NAD , Estudios de Cohortes , NucleótidosRESUMEN
A previous in vivo study with rats suggested that a special milk protein drink manufactured using an acidification procedure to suppress the aggregation of milk proteins was absorbed quickly after feeding. We performed a randomized, double-blind, placebo-controlled, repeated-measure crossover study to investigate the short-term effects on cognitive performance in 29 healthy young adult men after they consumed this drink in the morning. After an overnight fast, subjects were tested for performance in the Uchidaâ»Kraepelin serial arithmetic test and the Stroop test as well as for subjective feeling, body temperature, and heart rate variability before and after consumption of either the acidified milk protein drink or an isoenergetic placebo drink. Subjects showed a significant improvement in performance in the Uchidaâ»Kraepelin test, the primary outcome measured, when they consumed the acidified milk protein drink compared with the placebo control condition. In addition, consumption of the acidified milk protein drink, compared with the placebo control, was associated with increases in vagally-mediated heart rate variability indices which, from recent theoretical perspectives, may reflect a higher ability to modulate cognitive and behavioral processes. There was no significant difference in subjective feelings and body temperature between the test drink conditions. These data suggest that consumption of the acidified milk protein drink may improve cognitive performance, with possible involvement of physiological systems that regulate cognition and behavior.
Asunto(s)
Cognición/efectos de los fármacos , Proteínas de la Leche/administración & dosificación , Adolescente , Adulto , Bebidas/análisis , Temperatura Corporal , Citratos/administración & dosificación , Ácido Cítrico/administración & dosificación , Estudios Cruzados , Método Doble Ciego , Electrocardiografía , Frecuencia Cardíaca/efectos de los fármacos , Humanos , Malatos/administración & dosificación , Masculino , Cooperación del Paciente , Citrato de Sodio , Test de Stroop , Encuestas y Cuestionarios , Resultado del Tratamiento , Vitamina B 6/administración & dosificación , Adulto JovenRESUMEN
Synapse formation requires the precise coordination of axon elongation, cytoskeletal stability, and diverse modes of cell signaling. The underlying mechanisms of this interplay, however, remain unclear. Here, we demonstrate that Strip, a component of the striatin-interacting phosphatase and kinase (STRIPAK) complex that regulates these processes, is required to ensure the proper development of synaptic boutons at the Drosophila neuromuscular junction. In doing so, Strip negatively regulates the activity of the Hippo (Hpo) pathway, an evolutionarily conserved regulator of organ size whose role in synapse formation is currently unappreciated. Strip functions genetically with Enabled, an actin assembly/elongation factor and the presumptive downstream target of Hpo signaling, to modulate local actin organization at synaptic termini. This regulation occurs independently of the transcriptional co-activator Yorkie, the canonical downstream target of the Hpo pathway. Our study identifies a previously unanticipated role of the Strip-Hippo pathway in synaptic development, linking cell signaling to actin organization.