The Effect of Carbohydrate-Restricted Diets on the Skin Aging of Mice.

Low-carbohydrate, high-protein diets, known as carbohydrate-restricted diets, are in contrast to the carbohydrate-centric meals typical of the Japanese diet. Carbohydrate-restricted 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 carbohydrate-restricted 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.

Miso (Fermented Soybean Paste) Suppresses Visceral Fat Accumulation in Mice, Especially in Combination with Exercise.

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.

Simultaneous Intake of Euglena gracilis and Vegetables Exerts Synergistic Anti-Obesity and Anti-Inflammatory Effects by Modulating the Gut Microbiota in Diet-Induced Obese Mice.

We determined whether the anti-obesity effect provided by the consumption of Euglena gracilis (Euglena), which is rich in insoluble dietary fiber, could be enhanced by the co-consumption of vegetables with an abundance of soluble dietary fiber. Nine-week-old male C57BL/6J mice were divided into five groups as follows: group 1 received a normal diet, group 2 received a high-fat diet, and groups 3, 4, and 5 received high fat diets 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 reduced visceral fat accumulation in obese mice, and co-consumption of vegetables enhanced this effect. Consumption of Euglena with vegetables reduced adipocyte area, suppressed the expression of genes related to fatty acid synthesis, upregulated genes related to adipocyte lipolysis, and suppressed serum markers of inflammation. Notably, we also observed an increase in the fraction of short-chain fatty acid-producing beneficial bacteria, a reduction in harmful bacteria that cause inflammation, and an increase in short-chain fatty acid production. Therefore, the co-consumption of vegetables enhanced the anti-obesity and anti-inflammatory effects of Euglena, likely by modulating the gut microbiota composition.

Effects of Japanese diet in combination with exercise on visceral fat accumulation.

OBJECTIVES: In our previous study, we showed that among Japanese diets from different time periods, the 1975 Japanese diet has the greatest health benefits and is the most effective to prevent obesity. In addition, exercise is also effective to reduce obesity. Therefore, we conducted a human clinical trial combining the 1975 Japanese diet and exercise and, as a result, found a reduction in body weight, visceral fat, and serum lipids. However, the mechanism of this phenomenon was not determined. Therefore, in this study, we examined this mechanism in mice using a diet that was similar to that used in the human trial. METHODS: The modern and 1975 Japanese diets were cooked, lyophilized, powdered, and fed freely to 5 wk old male C57 BL/6 J mice for 8 wk. In addition, the mice exercised on a treadmill. RESULTS: Total white adipose tissue weight decreased significantly due to the interaction between the 1975 Japanese diet and exercise. A histologic examination revealed that the hypertrophy of adipocytes was suppressed. To clarify this mechanism, the mRNA levels for lipid metabolism-related genes in epididymal adipose tissue were measured, and the mRNA level of hormone sensitive lipase (Hsl), which is related to lipolysis, was found to be significantly increased after intake of the 1975 Japanese diet combined with exercise. In the gut microbiota analysis, the Bacteroidetes to Firmicutes ratio, which is decreased in obese people, was increased by the 1975 Japanese diet and exercise. At the genus level, there was an increase in butyrate-producing bacteria as a result of the 1975 Japanese diet intake and exercise. CONCLUSIONS: A combination of the 1975 Japanese diet and exercise increased lipolysis in white adipose tissue and increased butyrate-producing bacteria in gut microbiota, and thereby suppressed fat accumulation.

Fermented Soybean Suppresses Visceral Fat Accumulation in Mice.

SCOPE: Mice are fed a soybean diet before or after fermentation in the present work to allow direct comparison of the antiobesity effect of fermentation. METHODS: C57BL6J mice were fed high-fat diets containing boiled soybeans (prefermentation) or Natto (postfermentation) for 4 weeks. Prefermented cooked soybeans or Natto was added at levels of 2.5 and 5%, which are the amounts that can be ingested in a normal diet once and twice a day. In addition, mice gut microbiota from fecal samples were analyzed to explore the mechanisms of effects caused by fermentation. RESULTS: Natto intake significantly reduced visceral fat in a dose-dependent manner, inhibited hypertrophy of adipocytes, improved carbohydrate metabolism, and reduced oxidative stress. These effects were seen in mice fed soybeans before fermentation, but were stronger in mice fed Natto. Therefore, soybean intake has beneficial effects and fermentation of soybeans enhances these effects. Natto was found to suppress fatty acid synthesis and promote fatty acid catabolism in the liver. These effects were also stronger with Natto compared with soybeans before fermentation. In addition, Natto had more potent beneficial effects on gut microbiota compared to soybeans. CONCLUSIONS: These results suggest that Natto intake supports maintenance of health.