Cellular NAD⁺ is continuously degraded and synthesized under resting conditions. In mammals, NAD⁺ synthesis is primarily initiated from nicotinamide (Nam) by Nam phosphoribosyltransferase, whereas poly(ADP-ribose) polymerase 1 (PARP1) and 2 (PARP2), sirtuin1 (SIRT1), CD38, and sterile alpha and TIR motif containing 1 (SARM1) are involved in NAD⁺ breakdown. Using flux analysis with ²H-labeled Nam, we found that when mammalian cells were cultured in the absence of Nam, cellular NAD⁺ levels were maintained and NAD⁺ breakdown was completely suppressed. In the presence of Nam, the rate of NAD⁺ breakdown (R_B) did not significantly change upon PARP1, PARP2, SIRT1, or SARM1 deletion, whereas stable expression of CD38 did not increase R_B. However, R_B in PARP1-deleted cells was much higher compared with that in wild-type cells, in which PARP1 activity was blocked with a selective inhibitor. In contrast, R_B in CD38-overexpressing cells in the presence of a specific CD38 inhibitor was much lower compared with that in control cells. The results indicate that PARP1 deletion upregulates the activity of other NADases, whereas CD38 expression downregulates the activity of endogenous NADases, including PARP1 and PARP2. The rate of cellular NAD⁺ breakdown and the resulting NAD⁺ concentration may be maintained at a constant level, despite changes in the NAD⁺-degrading enzyme expression, through the compensatory regulation of NADase activity.

The bioavailability of natural folates is 50% lower than that of synthetic folic acid (FA); however, it remains unclear whether this value is universally applicable to all foods. Therefore, the present study investigated the bioavailability of folate from spinach using multiple biomarkers in a folate depletion-repletion mouse model. Mice were fed a folate-deficient diet for 4 wk and subsequently divided into three groups: folate-deficient, FA, and spinach folate. The folate repletion group received either FA or spinach folate at 2 mg/kg diet for 9 d. On the 7th day of repletion, half of each group underwent low-dose total body X-ray irradiation to induce chromosomal damage in bone marrow. Folate bioavailability biomarkers included measurements of folate levels in plasma, liver, and bone marrow along with an analysis of plasma homocysteine levels and chromosome damage, both of which are functional biomarkers of body folate. The consumption of a folate-deficient diet led to decreased tissue folate levels, increased plasma homocysteine levels, and chromosomal damage. Repletion with spinach folate restored folate levels in plasma, liver, and bone marrow to 69, 13, and 68%, respectively, of FA levels. Additionally, spinach folate repletion reduced plasma homocysteine levels and chromosome damage to 83% and 93–117%, respectively, of FA levels. Collectively, the present results demonstrated that the bioavailability of spinach folate exceeded 83% of FA, particularly when assessed using functional biomarkers.

Chronic inflammation in adipose tissue is thought to contribute to insulin resistance, which involves the gut microbiota. Our previous studies have demonstrated that ingestion of 1-kestose can alter the gut microbiota composition, increase cecal butyrate levels, and improve insulin resistance in Otsuka Long-Evans Tokushima Fatty (OLETF) rats. Additionally, we found that 1-kestose supplementation ameliorated insulin resistance in obese rat models fed a high-fat diet (HFD), although the effects of 1-kestose on the abundance of inflammation-related gene in adipose tissue and gut microbiota composition in these rats were not explored. This study aimed to investigate the impact of 1-kestose on these parameters in HFD-fed rats, compared to OLETF rats. Male Sprague-Dawley rats were divided into two dietary groups, control or HFD, for 19 wk. Each group was further subdivided to receive either tap water or tap water supplemented with 2% (w/v) 1-kestose throughout the study. We evaluated gene expression in adipose tissue, as well as short-chain fatty acids (SCFAs) levels and microbial composition in the cecum contents. 1-Kestose intake restored the increased relative abundance of tumor necrosis factor (Tnf) mRNA in adipose tissue and the reduced level of butyrate in the cecum contents of HFD-fed rats to those observed in control diet-fed rats. Additionally, 1-kestose consumption changed the composition of the gut microbiota, increasing Butyricicoccus spp., decreasing UGC-005 and Streptococcus spp., in the cecum contents of HFD-fed rats. Our findings suggest that 1-kestose supplementation reduces adipose tissue inflammation and increases butyrate levels in the gut of HFD-fed rats, associated with changes in the gut microbiota composition, distinct from those seen in OLETF rats.

Recently, we have demonstrated that mice, cultured embryos in α-minimum essential medium (αMEM) and subsequent fed a high-fat, high-sugar diet, developed steatohepatitis. In this study, we investigated using these samples whether the expression of lipid droplet formation genes in the liver is higher in MEM mice, whether these expressions are regulated by histone acetylation, writers/readers of histone acetylation, and the transcriptional factors of endoplasmic reticulum stress. Mice were produced by two-cell embryos in αMEM or standard potassium simplex-optimized medium (control) in vitro for 48 h, and implanted into an oviduct for spontaneous delivery. MEM and control-mice were fed a high-fat, high-sugar diet for 18 wk, and then liver samples were collected and analyzed by histology, qRT-PCR, and chromatin immunoprecipitation assay. Gene expression of Cidea, Cidec, and Plin4 were higher in MEM mice and histone H3K9 acetylation, BRD4, and CBP were higher in MEM mice than in control mice around those genes. However, the binding of endoplasmic reticulum stress-related transcription factors (ATF4, CHOP and C/EBPα) around those genes in the liver, was not clearly differed between MEM mice and control mice. The increased expression of Cidea, Cidec and Plin4 in the liver, accompanied by the development of steatohepatitis in mice induced is positively associated with increased histone H3K9 acetylation and CBP and BRD4 binding around these genes.

Malnutrition in children with cancer is associated with poor prognosis. This study aimed to determine whether nutritional support team (NST) interventions prevent adverse events and improve the nutritional status in pediatric patients admitted for cancer treatment. This was a historical cohort study of pediatric patients with acute lymphocytic leukemia, acute myeloid leukemia, neuroblastoma, or brain tumor who received chemotherapy or underwent hematopoietic stem cell transplantation. Patients admitted between June 2013 and October 2014 were classified into the intervention group. Those admitted between January 2011 and December 2012 were classified into the control group. We created a homogeneous probability model using the inverse probability of treatment weighting method, and compared outcomes. A total of 75 patients were included in the study (38 and 37 in the intervention and control groups, respectively). The intervention group had significantly fewer incidents of nothing by mouth (nil per os [NPO]) (p=0.037) and days of NPO (p=0.046) than the control group. There was no significant difference between the intervention and control groups regarding the change in body mass index z-score between admission and discharge (p=0.376). NST interventions for children with cancer were associated with a reduction in the number of NPO occurrences and NPO days. These findings suggest that NST interventions contribute to continued oral intake.

The composition of gut microbiota is determined not only by genetic factors but also by environmental factors, such as diet, exercise, and disease conditions. Among these factors, diet is crucial in changing the gut microbial composition. Dietary lipids composed of different fatty acids not only alter host metabolism but also have a significant impact on the composition of gut microbiota. However, the molecular mechanisms underlying the relationship between these host effects and their impact on gut microbiota remain unclear. Here, we demonstrated that intake of different dietary lipids improved glucose tolerance by modulating gut microbiota. The results of our analysis show that the taxa of bacteria that increase in number as a result of dietary lipid intake play an important role in glucose metabolism. Thus, we have identified a new mechanism underlying the function of dietary lipids in regulating glucose homeostasis. Our findings contribute to possible new methods to prevent and treat metabolic disorders by modifying the composition of gut microbiota.

Dairy products formulated with bioactives are widely distributed in Japan, but it remains to be clear whether a regular consumption of these products would help reduce the risks of incidental functional disability and dementia in older adults. This study aimed to investigate Japanese subjects aged ≥65 y (n=629) that routinely consumed three functional dairy products, a calcium-enriched milk supplemented with Bifidobacterium longum BB536, a yogurt supplemented with lactoferrin, B. longum BB536 and heat-killed Lacticaseibacillus paracasei MCC1849, and a drinkable yogurt supplemented with lactoferrin, B. longum BB536 and heat-killed L. paracasei MCC1849, through a home delivery service. Intake frequency and intake duration of these functional dairy products were compared with the risk scores of incident functional disability and dementia, developed by the Japan Gerontological Evaluation Study. In the participants aged <75 y, the incident functional disability risk was significantly maintained or decreased in the participants with the long intake duration level compared with the short intake duration level (OR, 95% CI: 0.48, 0.25–0.93). In the participants aged ≥75 y, the dementia risk was significantly maintained or decreased in the participants with the high intake frequency level compared with the low intake frequency level (OR, 95% CI: 0.46, 0.22–0.95). A high intake frequency or long term duration of these functional dairy products may be effective in preventing an aging-related increase in the risks of incident functional disability and dementia in older adults, but this warrants further investigation using different products containing different bioactives.

Dishcook is a new cooking system that allows individual cooking using a dedicated induction heater. This study investigated whether Dishcook use affects the nutritional value of individuals with intellectual disabilities. This study was conducted on users receiving support from a continuous-employment office in Obama City, Fukui Prefecture, in 2022. Of these participants, 18 (seven women and 11 men) who requested the use of the Dishcook were included in the analysis. The study period was from January to August 2023. The mean age was 48.72±16.24 y. A significant increase in the overall phase angles of the limbs was observed. Triglyceride, LDL cholesterol, HbA1c, and serum zinc levels improved in patients who used the Dishcook. The phase angle obtained using Bioelectrical Impedance Analysis also improved, indicating the usefulness of the Dishcook in treating metabolic diseases and the possibility of individualized nutritional management.

Ascorbic acid is essential for human health. As this vitamin is water-soluble, it cannot be stored in the body for a long time and is easily excreted in urine; therefore, it is necessary to ingest it in sufficient amounts every day. The fact that apples retain ascorbic acid in human bodies are known; however, this has not been experimentally demonstrated/documented. In this study, to clarify the effect of apple juice ingestion on the urinary excretion of ascorbic acid, we compared urinary ascorbic acid excretion in healthy women administered ascorbic acid alone or with apple juice. The experimental design was an unblinded randomized crossover study. Subjects ingested ascorbic acid in apple juice or ascorbic acid with water. Urine was collected after ingestion, and urinary ascorbic acid was measured. When ascorbic acid was ingested with apple juice, urinary excretion of ascorbic acid was significantly suppressed compared to when ascorbic acid was ingested alone. This suggests that apple juice intake can help retain ascorbic acid in the body.