Ayako Watanabe

Bio: Ayako Watanabe is an academic researcher from Nagoya University. The author has contributed to research in topics: Type 2 diabetes & Gut flora. The author has an hindex of 3, co-authored 5 publications receiving 14 citations.

Experimental Determination of the Threshold Dose for Bifidogenic Activity of Dietary 1-Kestose in Rats.

Abstract: 1-Kestose is a non-digestible oligosaccharide consisting of glucose linked to two fructose units. While 1-kestose is not digested in the small intestine of mammals, it is fermented in the ceca and colon, where the growth of bifidobacteria is promoted. In the present study, we assessed the threshold dose of dietary 1-kestose that increased cecal bifidobacterial levels in rats. Rats were fed experimental diets containing 0% to 0.3% 1-kestose for four weeks. The levels of the genus Bifidobacterium and total gut bacteria were significantly increased in cecal samples of rats fed the 0.3% 1-kestose diet. Further, a significant correlation between the dose of 1-kestose and the levels of cecal Bifidobacterium and total gut bacteria was observed. The minimum dose of dietary 1-kestose to induce significant bifidogenic activity in rats was 0.3% by weight in the diet.

Supplementation of 1-Kestose Modulates the Gut Microbiota Composition to Ameliorate Glucose Metabolism in Obesity-Prone Hosts.

Abstract: Insulin resistance leads to the onset of medical conditions such as type 2 diabetes, and its development is associated with the alteration in the gut microbiota. Although it has been demonstrated that supplementation with prebiotics modulates the gut microbiota, limited evidence is available for effects of prebiotics on insulin resistance, especially for humans. We investigated the prebiotic effect of 1-kestose supplementation on fasting insulin concentration in obesity-prone humans and rats. In the preliminary study using rats, the hyperinsulinemia induced by high-fat diet was suppressed by intake of water with 2% (w/v) 1-kestose. In the clinical study using obese-prone volunteers, the fasting serum insulin level was significantly reduced from 6.5 µU/mL (95% CI, 5.5-7.6) to 5.3 (4.6-6.0) by the 12-week intervention with supplementation of 10 g 1-kestose/day, whereas it was not changed by the intervention with placebo (6.2 µU/mL (5.4-7.1) and 6.5 (5.5-7.6) before and after intervention, respectively). The relative abundance of fecal Bifidobacterium was significantly increased to 0.3244 (SD, 0.1526) in 1-kestose-supplemented participants compared to that in control participants (0.1971 (0.1158)). These results suggest that prebiotic intervention using 1-kestose may potentially ameliorate insulin resistance in overweight humans via the modulation of the gut microbiota. UMIN 000028824.

1-Kestose supplementation mitigates the progressive deterioration of glucose metabolism in type 2 diabetes OLETF rats

Abstract: The fructooligosaccharide 1-kestose cannot be hydrolyzed by gastrointestinal enzymes, and is instead fermented by the gut microbiota. Previous studies suggest that 1-kestose promotes increases in butyrate concentrations in vitro and in the ceca of rats. Low levels of butyrate-producing microbiota are frequently observed in the gut of patients and experimental animals with type 2 diabetes (T2D). However, little is known about the role of 1-kestose in increasing the butyrate-producing microbiota and improving the metabolic conditions in type 2 diabetic animals. Here, we demonstrate that supplementation with 1-kestose suppressed the development of diabetes in Otsuka Long-Evans Tokushima Fatty (OLETF) rats, possibly through improved glucose tolerance. We showed that the cecal contents of rats fed 1-kestose were high in butyrate and harbored a higher proportion of the butyrate-producing genus Anaerostipes compared to rats fed a control diet. These findings illustrate how 1-kestose modifications to the gut microbiota impact glucose metabolism of T2D, and provide a potential preventative strategy to control glucose metabolism associated with dysregulated insulin secretion.

BDK Deficiency in Cerebral Cortex Neurons Causes Neurological Abnormalities and Affects Endurance Capacity.

Abstract: Branched-chain amino acid (BCAA) catabolism is regulated by its rate-limiting enzyme, branched-chain α-keto acid dehydrogenase (BCKDH), which is negatively regulated by BCKDH kinase (BDK). Loss of BDK function in mice and humans leads to dysregulated BCAA catabolism accompanied by neurological symptoms such as autism; however, which tissues or cell types are responsible for the phenotype has not been determined. Since BDK is highly expressed in neurons compared to astrocytes, we hypothesized that neurons are the cell type responsible for determining the neurological features of BDK deficiency. To test this hypothesis, we generated mice in which BDK deletion is restricted to neurons of the cerebral cortex (BDKEmx1-KO mice). Although BDKEmx1-KO mice were born and grew up normally, they showed clasped hind limbs when held by the tail and lower brain BCAA concentrations compared to control mice. Furthermore, these mice showed a marked increase in endurance capacity after training compared to control mice. We conclude that BDK in neurons of the cerebral cortex is essential for maintaining normal neurological functions in mice, and that accelerated BCAA catabolism in that region may enhance performance in running endurance following training.

Reply to Comment on Watanabe, A.; Kadota, Y.; Yokoyama, H.; Tsuruda, S.; Kamio, R.; Tochio, T.; Shimomura, Y.; Kitaura, Y. Experimental Determination of the Threshold Dose for Bifidogenic Activity of Dietary 1-Kestose in Rats. Foods 2020, 9, 4

Abstract: The manuscript entitled "Comment on Experimental Determination of the Threshold Dose for Bifidogenic Activity of Dietary 1-Kestose in Rats" by Shen et al [...].

Gut Microbiota: An Important Player in Type 2 Diabetes Mellitus

Abstract: Type 2 diabetes mellitus (T2DM) is one of the common metabolic diseases in the world. Due to the rise in morbidity and mortality, it has become a global health problem. To date, T2DM still cannot be cured, and its intervention measures mainly focus on glucose control as well as the prevention and treatment of related complications. Interestingly, the gut microbiota plays an important role in the development of metabolic diseases, especially T2DM. In this review, we introduce the characteristics of the gut microbiota in T2DM population, T2DM animal models, and diabetic complications. In addition, we describe the molecular mechanisms linking host and the gut microbiota in T2DM, including the host molecules that induce gut microbiota dysbiosis, immune and inflammatory responses, and gut microbial metabolites involved in pathogenesis. These findings suggest that we can treat T2DM and its complications by remodeling the gut microbiota through interventions such as drugs, probiotics, prebiotics, fecal microbiota transplantation (FMT) and diets.

Phenolic-rich apple extracts have photoprotective and anti-cancer effect in dermal cells

Abstract: Background Skin cancer is the most common type of malignancy in light-skinned populations and phenolics are promising anticarcinogenic agents. Purpose To characterise and evaluate the protective potential of apple extracts against the DNA damage caused by UV-radiation in culture of human fibroblasts as well as to verify the anticarcinogenic effect of these extracts in murine and human melanoma cells. Methods Acetone-ethanol extracts of apple were purified and fractionated by solid phase extraction. Four phenolic fractions (PF-I, PF-II, PF-III, PF-IV) and one Unfractionated Phenolics (UFP) were obtained. The presence of amygdalin, hydroxycinnamic acid, flavonols, flavanols and dihydrochalcones was confirmed by High-Performance Liquid Chromatography–Mass Spectrometry. Results Following 48 h exposure to UV-radiation, UFP, PF-III and PF-IV protected (14–34 %) fibroblast DNA against UV-radiation; the UFP and PF-IV, both at 31.25 μg.mL−1, showed high antiproliferative effect in murine melanoma cells (B16F10); UFP and PF-IV, both at 125 μg.mL−1, and PF-II, at 250 μg.mL−1, were effective against human melanoma cells (SK-Mel-103). Conclusions The results indicate that phenolic extracts from apple (Malus domestica Borkh cv. Gala) have potential for use in the formulation of cosmetic products and/or medicines for the protection of cellular DNA against UV radiation and for the treatment of melanoma.

Branched chain amino acids—friend or foe in the control of energy substrate turnover and insulin sensitivity?

Abstract: Branched chain amino acids (BCAA) and their derivatives are bioactive molecules with pleiotropic functions in the human body. Elevated fasting blood BCAA concentrations are considered as a metabolic hallmark of obesity, insulin resistance, dyslipidaemia, nonalcoholic fatty liver disease, type 2 diabetes and cardiovascular disease. However, since increased BCAA amount is observed both in metabolically healthy and obese subjects, a question whether BCAA are mechanistic drivers of insulin resistance and its morbidities or only markers of metabolic dysregulation, still remains open. The beneficial effects of BCAA on body weight and composition, aerobic capacity, insulin secretion and sensitivity demand high catabolic potential toward amino acids and/or adequate BCAA intake. On the opposite, BCAA-related inhibition of lipogenesis and lipolysis enhancement may preclude impairment in insulin sensitivity. Thereby, the following review addresses various strategies pertaining to the modulation of BCAA catabolism and the possible roles of BCAA in energy homeostasis. We also aim to elucidate mechanisms behind the heterogeneity of ramifications associated with BCAA modulation.

Supplementation of 1-Kestose Modulates the Gut Microbiota Composition to Ameliorate Glucose Metabolism in Obesity-Prone Hosts.

Abstract: Insulin resistance leads to the onset of medical conditions such as type 2 diabetes, and its development is associated with the alteration in the gut microbiota. Although it has been demonstrated that supplementation with prebiotics modulates the gut microbiota, limited evidence is available for effects of prebiotics on insulin resistance, especially for humans. We investigated the prebiotic effect of 1-kestose supplementation on fasting insulin concentration in obesity-prone humans and rats. In the preliminary study using rats, the hyperinsulinemia induced by high-fat diet was suppressed by intake of water with 2% (w/v) 1-kestose. In the clinical study using obese-prone volunteers, the fasting serum insulin level was significantly reduced from 6.5 µU/mL (95% CI, 5.5-7.6) to 5.3 (4.6-6.0) by the 12-week intervention with supplementation of 10 g 1-kestose/day, whereas it was not changed by the intervention with placebo (6.2 µU/mL (5.4-7.1) and 6.5 (5.5-7.6) before and after intervention, respectively). The relative abundance of fecal Bifidobacterium was significantly increased to 0.3244 (SD, 0.1526) in 1-kestose-supplemented participants compared to that in control participants (0.1971 (0.1158)). These results suggest that prebiotic intervention using 1-kestose may potentially ameliorate insulin resistance in overweight humans via the modulation of the gut microbiota. UMIN 000028824.

Macrophages rely on extracellular serine to suppress aberrant cytokine production

Abstract: A growing body of evidence indicates that cellular metabolism is involved in immune cell functions, including cytokine production Serine is a nutritionally non-essential amino acid that can be generated by de novo synthesis and conversion from glycine Serine contributes to various cellular responses, but the role in inflammatory responses remains poorly understood Here, we show that macrophages rely on extracellular serine to suppress aberrant cytokine production Depleting serine from the culture media reduced the cellular serine content in macrophages markedly, suggesting that macrophages depend largely on extracellular serine rather than cellular synthesis Under serine deprivation, macrophages stimulated with lipopolysaccharide showed aberrant cytokine expression patterns, including a marked reduction of anti-inflammatory interleukin-10 expression and sustained expression of interleukine-6 Transcriptomic and metabolomics analyses revealed that serine deprivation causes mitochondrial dysfunction: reduction in the pyruvate content, the NADH/NAD+ ratio, the oxygen consumption rate, and the mitochondrial production of reactive oxygen species (ROS) We also found the role of mitochondrial ROS in appropriate cytokine production Thus, our results indicate that cytokine production in macrophages is tightly regulated by the nutritional microenvironment