We investigated whether the difference in miso consumption between the Japanese diets of 1975 and 2010 has influenced the observed increase in diet-induced obesity. To recreate the 2010 and 1975 Japanese high-fat diets with the corresponding proportions of miso, freeze-dried miso was added to high-fat mouse feed at 1.6% and 2.6%, respectively. When 5-week-old male Institute of Cancer Research (ICR) mice were provided each of these diets ad libitum for 8 weeks, it was found that the white adipose tissue weight and adipocyte area were lower in mice receiving the 1975 diet than in those receiving the 2010 diet. Therefore, high miso consumption is one reason why the 1975 Japanese diet tended to not lead to obesity. Next, the combined effects of treadmill exercise and miso consumption were investigated. The mice were divided into three groups, which were provided either a high-fat diet (group C), a high-fat diet with exercise (group C + E), or a miso-supplemented high-fat diet with exercise (group M + E) for 8 weeks. In this experiment, the white adipose tissue weight and adipocyte area in group M + E were lower than in group C. When the mRNA expression of lipid metabolism-associated genes in adipose tissue was measured, we found that expression of Hsl (lipase, hormone sensitive), which is involved in lipolysis, and Pparγ (peroxisome proliferator activated receptor gamma), which regulates adipocyte differentiation upstream of Hsl, was increased in group M + E. These results clearly demonstrated that lipid accumulation in the adipose tissues is suppressed by miso consumption in combination with exercise.

We determined whether the benefits provided by the consumption of Euglena gracilis (Euglena), which is a unicellular photosynthesizing green alga and rich in insoluble dietary fiber paramylon, can be enhanced by the co-consumption of vegetables that are rich in soluble dietary fiber. Nine-week-old male C57BL/6J mice were divided into four groups: group 1 received normal diet, whereas groups 2, 3 and 4 received normal diet containing 0.3% paramylon, 1.0% Euglena, or 1.0% Euglena plus 0.3% vegetables (barley leaf, kale and ashitaba), respectively. Mice were fed ad libitum until 18 weeks of age. Euglena intake significantly decreased serum markers of inflammation and co-consumption of vegetables enhanced this reduction. Notably, we observed an increase in the fraction of beneficial bacteria producing short-chain fatty acids, a reduction in harmful bacteria that cause inflammation and an increase in short-chain fatty acid production. Visceral fat accumulation was also reduced. Subsequent analyses showed that co-consumption of Euglena with vegetables reduced adipocyte area, suppressed the expression of genes related to fatty acid synthesis and increased the expression of genes related to adipocyte growth and lipolysis. Therefore, co-consumption of Euglena with vegetables enhanced its anti-inflammatory effect and the inhibitory effect on visceral fat accumulation likely by modulating the composition of gut microbiota.

Low-carbohydrate, high-protein diets, known as carbohydrate-restricted diets, are in contrast to the carbohydrate-centric meals typical of the Japanese diet. Carbohydraterestricted diets were reported to reduce visceral fat, owing to which they have attracted attention and been widely implemented. If, as proposed, carbohydrate-restricted diets are effective in delaying senescence, then Japanese diets have a hidden potential to evolve further. However, long-term carbohydrate restriction in mice was reported to have a negative effect on the cardiovascular system, with shortening of lifespan due to activation of mechanistic target of rapamycin (mTOR). As a result, the safety of long-term adherence to carbohydraterestricted diets remains doubtful. Recently, we conducted a study using senescence-accelerated mouse-prone 8 (SAMP8) mice to examine the effects of a carbohydrate-restricted diet on aging and skin senescence, and to determine the effect of long-term carbohydrate restriction on the aging process in mice. Here, we discuss the safety of long-term carbohydrate restriction based on the findings obtained from animal studies.