Non-communicable metabolic diseases such as diabetes, obesity, and hypertension are associated with a number of serious complications, which have an adverse impact on healthy life expectancy. Since both genetics and lifestyle are involved, evidence-based measures derived from large-scale studies of various racial and regional populations are required. Some large-scale data analyses of Japanese subjects have revealed the complex relationship between obesity and the onset, remission, and prognosis of diabetes. In particular, even mild obesity is known to increase the risk of developing diabetes, thinness increases the rate of mortality in elderly patients, and weight loss contributes to diabetes remission in middle-aged obese diabetic patients. In terms of diet for diabetes, we have demonstrated the relationship between the intake ratio of carbohydrates and protein, salt intake, and the intake of vegetables, fruits, and dietary fiber and the risk of complications, and also revealed the benefits of applying these findings clinically, including supplementary exercise therapy and the use of ICT technology. It is expected that such efforts in nutritional epidemiology based on scientific data will lead to more effective dietary therapy in the future.

It has been reported that peptides, condensed amino acids, may provide health benefits, such as anti-hypertensive, anti-diabetic, and anti-dementia effects. One successful TOKUHO product is a sardine peptide that can modulate high blood pressure. However, the bioavailability of bioactive peptides still remains unclear due to a lack of appropriate analytical assay systems. In order to detect absorbed analytes in a small volume of blood, highly sensitive analytical assays that allow detection at ＞pmol/mL-plasma, such as fluorescence-derivatization column-switching HPLC, amine-derivatization-LC-MS/MS, and MS imaging for visualization of tissue distribution have been developed. In this review, the bioavailability of small peptides as intact forms and their physiological potentials are discussed.

Any decrease in the quantity or quality of skeletal muscle leads to a decrease in physical activity. Physical inactivity not only increases the risk of developing metabolic diseases such as obesity and type 2 diabetes, but also leads to a bedridden state in the elderly. Skeletal muscle health is regulated by food components that are ingested daily. Therefore, we have been conducting research to clarify the molecular mechanisms by which food components exert beneficial effects on skeletal muscle health. Here, we summarize the results obtained for three food components: (1) The isoflavone daidzein increased skeletal muscle mass by suppressing the expression of the deubiquitinase USP19 via estrogen receptor β in female mice, but not male mice; (2) Provitamin A, i.e., β-carotene and β-cryptoxanthin, suppressed soleus muscle atrophy in bedridden and aged model mice, respectively. Furthermore, transglutaminase 2, which was identified as a vitamin A-responsive gene, was involved in the β-carotene-induced increase in soleus muscle mass as a secreted protein; and (3) The fatty acid amide oleamide suppressed atrophy of the tibialis anterior muscle in mice housed in small cages to enforce sedentary behavior.

Senescence marker protein-30 (SMP30), originally discovered in rat liver, is a marker of aging. Importantly, SMP30 expression decreases with age in a sex hormone-independent manner and suppresses oxidative stress. Previously, however, no studies have investigated the regulation of SMP30 expression by nutrients or phytochemicals. In the present study, we demonstrated that epigallocatechin gallate (EGCG) and resveratrol positively regulated SMP30 expression in rat hepatoma-derived Fao cells. Furthermore, treatment with tert-butyl hydroperoxide, an oxidation promoter, decreased the expression of SMP30, whereas EGCG treatment inhibited these effects both in vivo and in vitro. Also, RSV suppressed the substantial downregulation of SMP30 expression caused by oxidative stress and hydrogen peroxide, leading to release of accumulated lactate dehydrogenase. The present findings offer new perspectives on the anti-aging properties of EGCG and RSV. Finally, the effects of ascorbic acid (AsA) deficiency on the relationship between SMP30 and acute liver injury were investigated in osteogenic disorder Shionogi rats, which have a hereditary defect in AsA biosynthesis. Importantly, the level of SMP30 protein in extracellular vesicles (EVs) was significantly increased under conditions of AsA deficiency. These results suggest that the release of SMP30 in EVs under AsA deficiency is involved in acute-phase responses. The findings of this study offer new perspectives on the anti-aging properties of SMP30 as a food factor, and also suggest that SMP30 in EVs could be used as a biomarker.

Chronic obesity is associated with an increased risk of developing type 2 diabetes, cardiovascular disease, and cognitive decline. Obesity can be attributed to hypertrophy and hyperplasia of adipocytes, as a result of a diet that is high in fat and also lack of exercise. Therefore, it can be argued that suppressing these factors would represent an effective preventive measure against obesity. On the other hand, since dysplasia of adipocytes causes modulation of hormone production balance, “qualitative control” as well as “quantitative control” of adipocytes is considered to be important for obesity prevention and health maintenance. In this study, methylxanthines, which are taste components, were examined to determine their effects on adipocytes in vitro and in vivo. This revealed the molecular mechanism by which methylxanthines regulate adipocyte characteristics. Furthermore, using affinity purification methods, we identified target proteins of methylxanthine in adipocytes. These results suggest that taste compounds might be novel food factors with anti-obesity properties.

The degradation of edible oils affects the taste and aroma of foods, but a fully effective control technology has not yet been established. The acid value (AV) is defined by ISO as the amount of potassium hydroxide (in milligrams) required to neutralize free fatty acids in 1 gram of oil, and is widely recognized as an indicator of triglyceride hydrolysis. In Japan, the AV is a key indicator for determining the discard point for frying oils. Through analysis of heated canola oil, we identified oleoyl-linoleoyl-(8-carboxyoctanoyl)-glycerol and dioleoyl-(8-carboxyoctanoyl)-glycerol, which, along with free fatty acids, contribute significantly to increased AV. This review discusses these findings and their application to frying oil management and development.

Tamoxifen (TAM) has been used universally for the treatment of estrogen-sensitive breast cancer, but it is also known to decrease the count of cells such as leukocytes by induction of off-target apoptosis. In this study, we examined the effects of lipids, a biological component related to the cytotoxicity of TAM, by observing apoptosis in monocytic leukemia cells (U937 cells) cultured in the presence of palmitic acid (PA), a saturated fatty acid. PA significantly suppressed TAM-induced apoptosis in U937 cells in terms of DEVDase activity and nuclear aggregation/fragmentation. In contrast, oleic acid (OA) had a weaker inhibitory effect. In addition, 17β-estradiol (E2) had no effect on apoptosis induced by TAM, nor did it induce apoptosis on its own. Mitochondrial analysis revealed that PA suppressed TAM-induced inhibition of respiratory chain complex I and II (CI, II) activity. These results suggest that PA may reduce the estrogen receptor (ER) -independent cytotoxicity of TAM.

Nutrient profile (NP) models, which classify or score foods according to their nutritional composition for healthy food selection and product improvement, are used worldwide. In Japan, a Japanese version of the NP model is being considered. For reference in developing this Japanese version, the present study summarized the various methods for setting threshold criteria. The data for establishing these criteria were based on the NP models used by other countries. This information was collected by an Internet survey of 18 models that set thresholds for each food category, as well as the websites of the respective guidelines and development organizations. Globally, ＞50％ of the countries used a certain percentage of the existing standards, such as the dietary reference intakes for each country as the threshold. Conversely, Asian countries tended to set thresholds for which some foods in specific categories would meet the standards based on nutrient databases. In formulating the Japanese version, it was considered necessary to set standards consistent with the dietary reference intakes in Japan, the nutritional composition of products, and harmony with the NP models used abroad.