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Fat-rich diets not only induce obesity in humans but also make animals obese. Therefore, animals that accumulate body fat in response to a high-fat diet (especially rodents) are commonly used in obesity research. The effect of dietary fat on body fat accumulation is not fully understood in zebrafish, an excellent model of vertebrate lipid metabolism. Here, we explored the effects of dietary fat and green tea extract, which has anti-obesity properties, on body fat accumulation in zebrafish. Adult zebrafish were allocated to four diet groups and over 6 weeks were fed a high-fat diet containing basal diet plus two types of fat or a low-fat diet containing basal diet plus carbohydrate or protein. Another group of adult zebrafish was fed a high-fat diet with or without 5% green tea extract supplementation. Zebrafish fed the high-fat diets had nearly twice the body fat (visceral, subcutaneous, and total fat) volume and body fat volume ratio (body fat volume/body weight) of those fed low-fat diets. There were no differences in body fat accumulation between the two high-fat groups, nor were there any differences between the two low-fat groups. Adding green tea extract to the high-fat diet significantly suppressed body weight, body fat volume, and body fat volume ratio compared with the same diet lacking green tea extract. 3-Hydroxyacyl-coenzyme A dehydrogenase and citrate synthase activity in the liver and skeletal muscle were significantly higher in fish fed the diet supplemented with green tea extract than in those fed the unsupplemented diet. Our results suggest that a diet rich in fat, instead of protein or carbohydrate, induced body fat accumulation in zebrafish with mechanisms that might be similar to those in mammals. Consequently, zebrafish might serve as a good animal model for research into obesity induced by high-fat diets.

To investigate the combined and separate effects of exercise and milk fat globule membrane (MFGM) supplementation on frailty, physical function, physical activity level, and hematological parameters in community-dwelling elderly Japanese women. A total of 131 frail, elderly women over 75 years were randomly assigned to one of four groups: exercise and MFGM supplementation (Ex+MFGM), exercise and placebo (Ex+Plac), MFGM supplementation, or the placebo group. The exercise group attended a 60-minute training program twice a week for three months, and the MFGM group ingested 1g of the MFGM supplement in pill form, daily for 3 months. The primary outcome measure was change in frailty status based on Fried's frailty phenotype. Secondary outcome measures included body composition, physical function and hematological parameters, and interview survey components assessing lifestyle factors. Participants were followed for 4 months post-intervention. Significant group × time interactions were observed for usual walking speed (P = 0.005), timed up & go (P<0.001), and insulin-like growth factor-binding protein 3/insulin-like growth factor 1 ratio (P = 0.013). The frailty components revealed that weight loss, exhaustion, low physical activity, and slow walking speed were reversed, but low muscle strength did not significantly changed. Frailty reversal rate was significantly higher in the Ex+MFGM (57.6%) than in the MFGM (28.1%) or placebo (30.3%) groups at post-intervention (χ2 = 8.827, P = 0.032), and at the follow-up was also significantly greater in the Ex+MFGM (45.5%) and Ex+Plac (39.4%) groups compared with the placebo (15.2%) group (χ2 = 8.607, P = 0.035). The exercise+MFGM group had the highest odds ratio (OR) for frailty reversal at post-intervention and follow-up (OR = 3.12, 95% confidence interval (CI) = 1.13-8.60; and OR = 4.67, 95% CI = 1.45-15.08, respectively). This study suggests that interventions including exercise and nutrition can improve frailty status. Statistically significant additive effects of MFGM with exercise could not be confirmed in this population, and further investigation in larger samples is necessary. The Japan Medical Association Clinical Trial Registry (JMACCT)JMA-IIA00069.

Melanin in the epidermis determines the wide variation in skin color associated with ethnic skin diversity. Ethnic differences exist regarding melanosome loss in keratinocytes, but the mechanisms underlying these differences, and their contribution to the regulation of skin color, remain unclear. Here, we explored the involvement of autophagy in determining skin color by regulating melanosome degradation in keratinocytes. Keratinocytes derived from Caucasian skin exhibit higher autophagic activity than those derived from African American (AA) skin. Furthermore, along with the higher autophagy activity in Caucasian skin–derived keratinocytes compared with AA skin–derived keratinocytes, Caucasian skin–derived keratinocytes were more sensitive to melanosome treatment as shown by their enhanced autophagic activity, which may reflect the substantial mechanisms in the human epidermis owing to the limitations of the models. Melanosome accumulation in keratinocytes was accelerated by treatment with lysosomal inhibitors or with small interfering RNAs specific for autophagy-related proteins, which are essential for autophagy. Furthermore, consistent with the alterations in skin appearance, the melanin levels in human skin cultured ex vivo and in human skin substitutes in vitro were substantially diminished by activators of autophagy and enhanced by the inhibitors. Taken together, our data reveal that autophagy has a pivotal role in skin color determination by regulating melanosome degradation in keratinocytes, and thereby contributes to the ethnic diversity of skin color.

Mice feed with coffee polyphenols (CPP, chlorogenic acid) and milk fat globule membrane (MFGM) has increased survival rates and helps retain long-term memory. In the cerebral cortex of aged mice, CPP intake decreased the expression of the proinflammatory cytokine TNF-α, and lysosomal enzyme cathepsin B. The suppression of inflammation in the brain during aging was thought to result in the suppression of the repressor element 1-silencing transcription factor (REST) and prevention of brain aging. In contrast, CPP increased the expression of REST, cAMP-responsive element binding (CREB) and transforming growth factor β1 (TGF-β1) in the young hippocampus. The increased expression of these factors may contribute to the induction of neuronal differentiation and the suppression of memory decline with aging. Taken together, these results suggest that CPP increases CREB in the young hippocampus and suppresses inflammation in the old brain, resulting in a preventive effect on brain aging. The endotoxin levels were not elevated in the serum of aged mice. Although the mechanism of action of MFGM has not yet been elucidated, the increase in survival rate with both CPP and MFGM intake suggests that adding milk to coffee may improve not only the taste, but also the function.

Hydroxyhydroquinone (HHQ) is an oxidative component produced by roasting coffee beans and has been reported to generate relatively large amounts of reactive oxygen species (ROS). In this study, we used senescence-accelerated mouse prone 8 (SAMP8) mice to determine whether HHQ consumption increases oxidative-stress-induced injury, because in SAMP8 mice, the activity of 8-oxoguanine DNA glycosylase 1, which repairs oxidative modifications in DNA, is decreased. The results showed that two out of twelve (16.7%) HHQ-treated mice presented polyuria and glucosuria around 2 months after the start of treatment, indicating that HHQ may act as a mutagen against SAMP8 mice, which is sensitive to oxidative damage. No abnormalities were observed in the chlorogenic acid (coffee polyphenol, CPP)-treated group. The concentration of hydrogen peroxide in the serum of SAMP8 mice was significantly higher than that in SAMR1 (senescence-resistant) control mice, and the concentration was further increased in the HHQ-treated group. CPP, when coexisting with HHQ at the rate contained in roasted coffee, decreased the amount of hydrogen peroxide in the serum of SAMP8 mice. Although CPP can act both oxidatively and antioxidatively as a polyphenol, CPP acts more antioxidatively when coexisting with HHQ. Thus, the oxidative effect of HHQ was shown to be counteracted by CPP.

Epidemiological and laboratory studies have shown that green tea and green tea catechins exert beneficial effects on a variety of diseases, including cancer, metabolic syndrome, infectious diseases, and neurodegenerative diseases. In most cases, (−)-epigallocatechin gallate (EGCG) has been shown to play a central role in these effects by green tea. Catechins from other plant sources have also shown health benefits. Many studies have revealed that the binding of EGCG and other catechins to proteins is involved in its action mechanism. Computational docking analysis (CMDA) and X-ray crystallographic analysis (XCA) have provided detailed information on catechin-protein interactions. Several of these studies have revealed that the galloyl moiety anchors it to the cleft of proteins through interactions with its hydroxyl groups, explaining the higher activity of galloylated catechins such as EGCG and epicatechin gallate than non-galloylated catechins. In this paper, we review the results of CMDA and XCA of EGCG and other plant catechins to understand catechin-protein interactions with the expectation of developing new drugs with health-promoting properties.

Postprandial energy metabolism, including postprandial hyperglycaemia, hyperinsulinaemia and hyperlipidaemia, is related to the risk for developing obesity and CVD. In the present study, we examined the effects of polyphenols purified from coffee (coffee polyphenols (CPP)) on postprandial carbohydrate and lipid metabolism, and whole-body substrate oxidation in C57BL/6J mice. In mice that co-ingested CPP with a lipid–carbohydrate (sucrose or starch)-mixed emulsion, the respiratory quotient determined by indirect calorimetry was significantly lower than that in control mice, whereas there was no difference in VO2 (energy expenditure), indicating that CPP modulates postprandial energy partitioning. CPP also suppressed postprandial increases in plasma glucose, insulin, glucose-dependent insulinotropic polypeptide and TAG levels. Inhibition experiments on digestive enzymes revealed that CPP inhibits maltase and sucrase, and, to a lesser extent, pancreatic lipase in a concentration-dependent manner. Among the nine kinds of polyphenols (caffeoyl quinic acids (CQA), di-CQA, feruloyl quinic acids (FQA)) contained in CPP, di-CQA showed more potent inhibitory activity than CQA or FQA on these digestive enzymes, suggesting a predominant role of di-CQA in the regulation of postprandial energy metabolism. These results suggest that CPP modulates whole-body substrate oxidation by suppressing postprandial hyperglycaemia and hyperinsulinaemia, and these effects are mediated by inhibiting digestive enzymes.

The decline in physical performance with increasing age is a crucial problem in our aging society. We examined the effects of resveratrol, a natural polyphenolic compound present in grapes, in combination with habitual exercise on the aging-associated decline in physical performance in senescence-accelerated prone mice (SAMP1). The endurance capacity of SAMP1 mice undergoing an exercise regimen (SAMP1-Ex) decreased over 12 weeks whereas that of SAMP1 mice fed 0.2% (w/w) resveratrol along with exercise (SAMP1-ExRes) remained significantly higher. In the SAMP1-ExRes group, there was a significant increase in oxygen consumption and skeletal muscle mRNA levels of mitochondrial function-related enzymes. These results suggest that the intake of resveratrol, together with habitual exercise, is beneficial for suppressing the aging-related decline in physical performance and that these effects are attributable, at least in part, to improved mitochondrial function in skeletal muscle.

The objective of this study was to clarify variations of the ceramide (CER) profile in human stratum corneum (SC) in different seasons and in different regions of the body and to estimate the contributions of CERs to the SC barrier and water-holding functions. Based on the information that there are great variations of SC functions among body sites, we compared the CER profiles obtained from ten different anatomical sites in healthy Japanese males in four seasons. Not only the physiological parameters of skin but also the CER profile showed body region and seasonal variations. The total CER level, the CER composition and the C34-CER[NS] species displayed strong correlations with the values of transepidermal water loss and capacitance throughout the body. Especially in the cheek, a strong correlation between the capacitance and the CER profile was observed. There were seasonal variations of the CER profile in the lip, upper arm and palm. Our results indicate that regional and seasonal variations of the CER profile may contribute to SC functions.

Senescence-accelerated mouse prone 10 (SAMP10) exhibits cerebral atrophy and depression-like behavior. A line of SAMP10 with spontaneous mutation in the Slc5a2 gene encoding the sodium-glucose cotransporter (SGLT) 2 was named SAMP10/TaSlc-Slc5a2slc (SAMP10-ΔSglt2) and was identified as a renal diabetes model. In contrast, a line of SAMP10 with no mutation in SGLT2 (SAMP10/TaIdrSlc, SAMP10(+)) was recently established under a specific pathogen-free condition. Here, we examined the mutation effect in SGLT2 on brain function and longevity. No differences were found in the survival curve, depression-like behavior, and age-related brain atrophy between SAMP10-ΔSglt2 and SAMP10(+). However, memory retention was lower in SAMP10-ΔSglt2 mice than SAMP10(+). Amyloid beta (A4) precursor-like protein 1 (Aplp1) expression was significantly lower in the hippocampus of SAMP10-ΔSGLT2 than in SAMP10(+) at 2 months of age, but was similar at 12 months of age. CaM kinase-like vesicle association (Camkv) expression was remarkably lower in SAMP10(+). These genes have been reported to be involved in dendrite function. Amyloid precursor proteins have been reported to involve in maintaining homeostasis of glucose and insulin. These results suggest that mutation in SGLT2 results in down-regulation of Aplp1 in young age, which can lead to poor memory retention in old age.