The effects of fiber intake from cereals, specifically barley and wholegrain wheat, on obesity parameters were investigated through human intervention studies. A series of experimental animal studies were also performed to investigate the mechanism responsible for the anti-obesity effects of barley. Our human intervention studies have revealed some evidence of effects such as: (1) suppression of the postprandial rise in blood glucose level (rice with barley and wholegrain wheat bread); (2) the maintenance of satiety (foods containing barley); (3) reduction of abdominal fat (rice with barley and wholegrain wheat bread); and (4) modification of gut microbiota (wheat bran and foods containing barley). Animal experiments have shown that both high- and low-molecular-weight barley β-glucans have anti-obesity effects. However, the former is due mainly to inhibition of dietary lipid absorption as a result of viscosity, and the latter to the action of short-chain fatty acids through intestinal fermentation. It was confirmed that the improvement of glucose intolerance resulting from intake of barley flour was attributable to an increase of short-chain fatty acids as a result of intestinal fermentation, thus increasing the secretion of glucagon-like peptide-1 (GLP-1).

Skeletal muscle is the largest organ in the human body, playing important roles in exercise, energy expenditure and glucose/amino acid metabolism. Appropriate exercise coupled with sufficient nutrition increases muscle mass. In contrast, bedrest, aging, cancer, and other diseases lead to muscle atrophy, thus decreasing energy expenditure (leading to obesity) and glucose uptake, increasing the blood glucose level (resulting in diabetes) and reducing the quality of life. We have been investigating the role of a transcription factor, FOXO1, in regulation of skeletal muscle metabolism. In particular, since FOXO1 gene expression is induced by energy deprivation, we have produced transgenic mice overexpressing FOXO1 and found that they exhibit muscle atrophy. In addition to FOXO1, transcriptional coactivators, PGC1s, also play an important role in muscle metabolism. PGC1α expression increases in skeletal muscle upon exercise, leading to an increase of mitochondria in skeletal muscle and formation of red/slow fibers. Thus, we have been investigating in detail the mechanisms of muscle metabolism in vivo and in vitro, focusing on FOXO1 and PGC1α/PGC1β as major regulators. We hope to clarify the mechanisms that operate to prevent atrophy and dysfunction of skeletal muscle, coupled with a better understanding of the utility of functional foods for prevention and/or alleviation of these conditions.

We aimed to reveal why food-derived factors such as plant pigments prevent obesity and diabetes. Anthocyanins are unstable plant pigments that degrade at neutral pH. Accordingly, they have been considered to have no significant bioactivity in vivo. However, we previously reported that anthocyanins are directly absorbed into blood and that metabolites (or degradation products) derived from them are generated in the body. We also reported that dietary anthocyanins significantly suppressed body fat accumulation and improve glucose tolerance. In our studies of curcumin, we found that a highly bioavailable curcumin formulation significantly induced the formation of beige adipocytes. Moreover, we clarified that artepillin C (ArtC, a propolis-derived component) induced beige adipocyte formation and thermogenesis in association with the uncoupling protein 1-independent pathway. We also reported that co-administration of curcumin and ArtC significantly induced beige adipocyte formation. Furthermore, administration of an amino acid mixture combined with exercise synergistically induced beige adipocyte formation, indicating that a combination of food-derived factors and exercise offers a unique biological response for induction of beige adipocyte formation, which may be involved in increasing energy expenditure. These results provide a basis for the promotion and development of new functional research on food-derived factors.

Prevention of frailty is an important issue in Japan. So far, there have been various reports on the factors that can reduce frailty, but only a few have focused on “diet”, and most are from Western countries where food culture and disease structure differ from those in Japan. The author conducted a nutritional epidemiological study to clarify diets that would be effective for preventing frailty. A prospective cohort study of community-dwelling Japanese elderly revealed that a high intake of animal-derived protein was associated with maintenance of higher-level functional decline after seven years. We also focused on anemia, which is a risk factor for frailty, and performed an analysis using data from National Health and Nutrition Surveys in Japan. It was clarified that diet patterns centered on animal products are associated with anemia risk reduction. Furthermore, the author focused on Shiga Prefecture, where life expectancy has rapidly increased in recent years, and clarified that the mortality rate there is lower due to a combination of multiple lifestyle-related factors. Furthermore, it was revealed that the greater the combination of these multiple lifestyle-related factors, there would be a greater number of people with a high subjective sense of health among the citizens of the prefecture. From the above results, the author has clarified that combination of an animal protein-centered diet with multiple lifestyle-related factors at an earlier stage might contribute to prevention of frailty.

Toxicological effects of polycyclic aromatic hydrocarbons (PAHs) are mediated mainly by the aryl hydrocarbon receptor (AhR). Therefore, reduction of AhR activity is a promising strategy for prevention of xenobiotic-induced toxicity. Activation of nuclear factor-erythroid 2-related factor 2 (Nrf2) results in enhanced antioxidant capacity and protection against environmental stressors by inducing phase II drug-metabolizing enzymes. The author revealed that luteolin and kaempferol coordinately prevent AhR-induced phase I drug-metabolizing enzyme, and a physiological concentration of luteolin, achievable from dietary consumption, activated Nrf2. Moreover, B[a]P-induced AhR activation caused lipid accumulation in the liver through circadian disruption; however, luteolin and kaempferol inhibited the circadian disruption caused by AhR activation. These results indicate that luteolin and kaempferol enhance biological defense function against xenobiotic-induced toxicity through the regulation of the drug metabolism system.

Brown adipose tissue (BAT) is a site responsible for non-shivering thermogenesis during cold exposure, contributing to the control of body temperature and adiposity. In humans, although a decrease of BAT activity with aging is associated with the development of obesity, chronic activation of BAT through repeated cold exposure can re-activate BAT, thereby decreasing body fat mass. To explore practical anti-obesity strategies that could be an alternative to cold exposure, we focused on food ingredients exerting agonistic activity against temperature-sensitive TRP channels. We then investigated the thermogenic effects of non-pungent capsaicin analogs (capsinoids) and green tea catechins, both of which can stimulate temperature-responsive TRP channels, and their relationship to BAT activity in healthy volunteers. We found that single ingestion of capsinoids or catechins significantly increased energy expenditure in subjects with active BAT, but not in those without. Moreover, repeated ingestion of these substances increased BAT-dependent thermogenic capacity even in individuals who had lost their BAT activity, suggesting successful recruitment of BAT. Additionally, through comprehensive analysis of circulating metabolites in mice and humans, we searched for new nutritional factors for control of BAT function and identified branched-chain amino acids as a key energy substrate for BAT thermogenesis. These our findings support the development of practical, efficient dietary regimens capable of boosting BAT thermogenesis and preventing lifestyle-related diseases.

With the global increase in the aged population, the development of cognition-enhancing foods that can be taken safely and reliably is attracting interest. Fermented milk is considered to have beneficial effects on health, and studies of its physiological functions have been conducted. Initial studies showed that sour milk made by fermenting skimmed milk with Lactobacillus helveticus was effective in improving cognitive function. The major effective component was the 19-residue peptide NIPPLTQTPVVVPPFLQPE (lactononadecapeptide, LNDP), derived from milk beta-casein. To further evaluate the benefits of LNDP, several clinical trials have now been conducted on the effects of LNDP-containing food on cognitive function in healthy subjects, using a range of subjects, intake periods, and neuropsychological evaluations. Consumption of food containing LNDP (2.1-4.2 mg/day for 8-24 weeks) has been demonstrated to maintain cognitive functions such as attention, information processing ability, and memory. Based on these results, LNDP has been put to practical use in foods with functional claims and will contribute to the maintenance and promotion of health in an aging society.

With the clarification of the entire human genome, research utilizing genomic information has become possible, and many studies have been reported. In addition, the development of genome analysis technology has led to the emergence of services that provide genome analysis for individuals, thus allowing them to have information on their own genome. Here, we provide an overview of the genome database for a personal genome service we have developed, which has potential for research utilization, and describe results of research in the field of food and nutrition for studies that have actually utilized the database. In addition, we describe the advantages of an internet cohort developed using this personal genome service as well as future possibilities beyond the use of big data in the life sciences. Issues that have emerged in the course of providing such a personal genome service are also addressed.