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Articles by Toshiro Arai
Total Records ( 11 ) for Toshiro Arai
  Nobuko Mori , Peter Lee , Ichiro Yamamoto , Satoshi Nozawa and Toshiro Arai
  The aim of this study was to determine what insulin-induced daily changes occur with adiponectin, Tumor Necrosis Factor-alpha (TNF-α) and other relevant lipid metabolic parameters such as Free Fatty Acid (FFA), Total Cholesterol (T-Cho) and Triglyceride (TG) levels in dogs suffering from type 1 Diabetes Mellitus (T1DM). Six dogs were treated with insulin injections at the Nippon Veterinary and Life Science University Animal Clinical Center for T1DM. They were clinically diagnosed as T1DM by signs of polydipsia, polyuria, glycosuria and high fasting plasma glucose (over 250 mg dL-1). Blood samples of dogs were collected twice a day, before breakfast and after 6 hours of insulin injection. As results, post-insulin treatment value of TG, BUN, creatinin and chyromicron significantly increased, whereas ALT, ALP, protein and FFA significantly decreased post treatment. Significant reductions in total cholesterol, Very Low- Density Lipoprotein-cholesterol (VLDL) and Low-Density Lipoprotein-cholesterol (LDL) concentrations were also observed. Phospholipid Transfer Protein (PLTP) activity increased post-insulin treatment. The increase in Cholesteryl Ester Transfer Protein (CETP) activity was significant. Remarkably, insulin treatment reduced plasma adiponectin levels in T1DM dogs. Insulin resistance results in an increased risk of atherosclerosis on a long term basis as evidenced by atherogenicity markers of the plasma lipoprotein profile such as increased CETP and PLTP activities. Under obese condition adiponectin has been shown to negatively correlate with several inflammatory mediators (IL-1β, IL-6, IL-8, TNF-α). Low-grade chronic systemic inflammation has been associated with obesity potentially leading to insulin resistance.
  Megumi Fujiwara , Toko Sato , Hiroyuki Tazaki , Ichiro Yamamoto , Koh Kawasumi and Toshiro Arai
  Hyperlipidemia refers to increase of triglyceride (TG) and/or total cholesterol (T-cho) in blood. Fatty Acids (FAs) have important roles in the lipid metabolism. The aim of this study was to determine the FA composition of plasma lipid fractions in dogs with hyperlipidemia and to evaluate the FA composition as a new diagnostic marker for obesity at early stage. Thirty-nine dogs were classified into healthy or hyperlipidemia based on the criteria to diagnose hyperlipidemia. The blood biochemical values, such as TG, T-cho, glucose, insulin, adiponectin and Non-Esterified Fatty Acid (NEFA) were measured. FA composition profile was performed on GC/MS system. The values of plasma TG, insulin and NEFA of the hyperlipidemia group were significantly higher than that of control group. Hyperlipidemia group tended to show lower concentration of adiponectin. It was found that only the levels of TG and NEFA, but not T-cho increased significantly in early stage of hyperlipidemia. In hyperlipidemia group, percentages of myristic acid (C14:0), parmitoleic acid (C16:1) and oleic acid (C18:1) increased in total FAs. And the percentage of C18:1 increased in NEFA. Indeed, the higher level of insulin and lower adiponectin concentration were seen in hyperlipidemia group. These results suggest that appearance of insulin resistance may be the result of increases of certain FAs in early stage of insulin resistance.
  Nobuko Mori , Hiroshi Takemitsu , Yuki Okada , Ichiro Yamamoto and Toshiro Arai
  Many veterinarians feel that obese dogs are increasing in prevalence worldwide. However, no data are available; thus, it is difficult to distinguish overweight from obesity as a sign of metabolic syndrome. The objectives are (1) To reveal the ratio of overweight and obese house dogs in Japan; and (2) To investigate differences in breed, gender, body condition and age of various purebreds on healthy dogs. Twelve metabolic parameters were assayed in 888 healthy dogs. The data were analyzed from various viewpoints of age, gender, Body Condition Score (BCS), castration and spay and breeds. The ratio of obese dogs was approximately 27% of all dogs examined. When the effects of aging were assessed, older females were found to be more affected by aging than males. In particular, lipid metabolism parameters, such as triglycerides (TG), Total Cholesterol (T-cho) and Free Fatty Acids (FFA) as well as insulin concentrations in female dogs >11 years old were the highest of all age groups. Because T-cho and insulin concentrations in BCS4 dogs were significantly high, these parameters could be useful as obesity markers in healthy dogs. Creatinine concentrations in small breed dogs, such as Beagles, Cavaliers, Chihuahuas, Miniature dachshunds, Pomeranians, Shih tzus and Yorkshire terriers, were lower than those in middle-sized and large-sized dogs. TG and FFA levels in neutered dogs were significantly higher than those in unaltered dogs. In future, it will be important to measure and assess metabolic parameters in healthy dogs to identify differences among different regions.
  Gebin Li , Peter Lee , Yuki Okada , Ichiro Yamamoto , Toshiro Arai and Nobuko Mori
  The objective of this study was to determine whether Peripheral Blood Leukocytes (PBL) are sensitive enough to detect early signs of diet induced obesity related changes occurring in insulin sensitive tissues, such as abdominal omental and subcutaneous adipose, liver and skeletal muscle, by comparing transcriptome profiles of insulin signaling (IRS-1, IRS-2 and PI3-K p85 α), adiponectin signaling (AdipoR1 and AdipoR2), energy homoeostasis (G6PDH and MDH) and sterol metabolism (FASN) genes as determined by RT-PCR in cats fed on High Fat (HF) diet. Regarding PBL concordance, using a HF diet induced obesity cat model, out of seven genes examined, concordance was observed with ~60% (5 out of 8) of them (IRS-1, IRS-2, Adipo-R1, Adipo-R2 and MDH) between PBL and tissue transcriptomes. HF diet cat PBL IRS-1 and IRS-2 mRNA expression were both reduced, when compared to control diet which was in concordance with reduced IRS-1 and IRS-2 mRNA expression in both abdominal and subcutaneous adipose of HF diet cats. Similar to IRS-1 and IRS-2, AdipoR1 and AdipoR2 mRNA expression in HF diet cats was also reduced, when compared to control diet which was in concordance with reduced AdipoR1 and AdipoR2 in liver and skeletal muscle, respectively of HF diet cats. Lastly, PBL MDH mRNA expression was reduced and was concordant with reduced mRNA expression in liver and skeletal muscle. Overall, our results demonstrate that PBL are sufficiently sensitive to high fat diet induced alterations to transcriptomes of insulin sensitive tissues and can serve as surrogate tissue for various insulin sensitive tissues.
  Nobuko Mori , Gebin Li , Megumi Fujiwara , Shingo Ishikawa , Koh Kawasumi , Ichiro Yamamoto and Toshiro Arai
  The prevalence of obese cats has increased because of over calorie diet and physical inactivity. Obesity has been found to be associated with oxidative stress and Reactive Oxygen Species (ROS). Unfortunately oxidative stress status at the early phase of obesity in high fat fed cats is not well understood. The objectives of this study were (1) To evaluate lipid and glucose metabolism using enzymatic, hormonal and oxidative stress biomarkers at the early obese phase of cats fed on a high-fat diet and (2) To identify rapidly changing variables to use as a diagnostic marker for lipid metabolic disorders in cats. Total 13 domestic female cats were divided into two groups which were fed on control and high-fat diet for eight weeks, respectively. After the feeding period, they were compared in metabolic variables and oxidative stress markers in plasma and tissues. As results, High-fat diet including much long chain fatty acids promoted rapid changes in lipid metabolism, particularly accelerated β-oxidation of fatty acids and oxidative stress in the liver of the cats. G6PD, GPx and SOD were increased in the liver. Insulin resistance was not apparent at the early phase of obesity in cats. Plasma activities of SOD also increased at the early phase of obesity in cats. Remarkable alternation for oxidative stress in liver was observed at the early phase of obesity in cats fed on high fat diet and SOD may be a potential marker of the early phase of obesity in cats.
  Koh Kawasumi , Yuki Okada , Nanae Kashiwado , Eiji Iwazaki , Nobuko Mori , Ichiro Yamamoto and Toshiro Arai
  The efficiency of licorice flavonoid supplement as anti-obesity substance was investigated in 14 client-owned dogs. This flavonoid supplement reduced whole and visceral fat in overweight humans. All experimental dogs were given the supplement at a dose of 10 mg kg-1 day-1 in the evening with food for 8 weeks. After 8 weeks post-administration, the body weight was decreased in 11 animals (78.6%). The decreasing rate was 2.51±0.6% (Mean±SE). Serum glucose (GLU), Triglyceride (TG), Malondialdehyde (MDA) concentrations and aspartate aminotransferase (AST), Alanine aminotransferase (ALT), Glutathione peroxidase (GSHPx) activities were decreased but the changes were not statistically significant. On the contrary, serum adiponectin (ADN) concentrations, though statically significance was not seen, tended to increase after 8 weeks post-administration of the supplement compared to those in baseline. In conclusion, the licorice flavonoid supplement was suggested to show anti-obesity effect accompanied with improvement of lipid metabolism in tissues of dogs.
  Makoto Habara , Makoto Tamanuki , Shingo Ishikawa , Hiroshi Takemitsu , Nobuko Mori , Yuki Okada , Nobuhiro Nakao , Koh Kawasumi , Katsumi Ishioka , Toshiro Arai and Ichiro Yamamoto
  G-protein-coupled receptors (GPRs) 40 and 120 are members of the Free Fatty Acid (FFA) receptor group and are termed FFAR1 and FFAR4, respectively. The aim of this study was to clone cat GPR40 and GPR120 cDNAs in several tissues. There was high sequence homology to other mammalian GPR40 and GPR120, with encoding 320 and 361 amino acid residues, respectively. Cat GPR40 encoded extra 21 amino acid residues in the C-terminal cytoplasmic region. Quantitative RT-PCR revealed expression of GPR40 mRNA in the duodenum, liver and pancreas. The GPR120 mRNA was expressed in adipose tissues, cerebral cortex and colon. In conclusion, GPR40 and GPR120 were well conserved and were expressed in cat tissues with different distribution patterns.
  Nobuko Mori , Koh Kawasumi , Tomoko Suzuki , Ichiro Yamamoto , Motoo Kobayashi and Toshiro Arai
  In this study, researchers attempted to establish temporary criteria for Metabolic Syndrome (MS) diagnosis in cats. To verify the usefulness of the selected criteria, we investigated changes in plasma glucose, Triglyceride (TG), Total Cholesterol (TC), Alanine Aminotransferase (ALT) insulin and adiponectin levels as diagnostic factors in 50 clinically healthy cats. Cats with obesity as an essential factor in addition to any two of the three conditions, namely increased plasma glucose levels, elevated TG and/or TC levels and higher ALT activity were diagnosed with MS. Presence of additional factors such as reduced plasma adiponectin and/or raised insulin levels, confirmed the MS diagnosis. Based on these criteria, 9 (18.0%) cats were diagnosed with MS. In these cats, the plasma glucose, TC and ALT levels were significantly higher than those in the control cats (n = 41) without MS. MS was not detected in cats with body condition score <3 and the occurrence rate of MS was the highest in 5-10 years old cats. In the MS cats, reduced plasma adiponectin levels appeared to be an essential factor that defined the early stage of the disease.
  Nobuko Mori , Koh Kawasumi and Toshiro Arai
  Plasma metabolite concentrations reflect changes in the energy metabolic and physical conditions of animals with metabolic disorders. A reduced adiponectin level in humans and rodents is the critical factor associated with the pathogenesis of obesity-associated atherosclerosis, insulin resistance and type 2 diabetes mellitus. Appropriate plasma metabolic markers appear to be useful for the early diagnosis of latent metabolic disorders with no clinical signs in animals. The aim of this study was to assess changes in the values of plasma metabolic markers in healthy ageing dogs. Significant differences were observed in the plasma insulin and total cholesterol concentrations in healthy dogs of different genders and ages. Adiponectin concentrations peaked at a young age and decreased with ageing. Apparently, insulin increased according to age. Plasma insulin concentrations were particularly influenced significantly by age as well as glucose and triglyceride levels whereas adiponectin concentrations were affected by gender on multiple linear regressions for all factors. No criteria exist for the early diagnosis of latent metabolic disorders without remarkable signs regarding age and gender in dogs. Thus, in case of dogs, it may be necessary to set up improved age-dependent criteria for metabolic disorders with changes in plasma insulin concentrations.
  Koh Kawasumi , Tomoko Suzuki , Megumi Fujiwara , Nobuko Mori , Ichiro Yamamoto and Toshiro Arai
  Researchers attempted to establish temporary criteria for Metabolic Syndrome (MS) diagnosis in dogs. To verify the usefulness of the selected criteria, researchers measured plasma Glucose (GLU), Triglyceride (TG), Total Cholesterol (TC), Non-Esterified Fatty Acid (NEFA), Alanine Aminotransferase (ALT) and insulin levels as diagnostic markers in 105 clinically healthy dogs. Dog with obesity as an essential factor (BCS = 3.5) in addition to any two of the following three factors 1-3 namely increased plasma GLU levels (≥120 mg dL-1), hyperlipidemic condition, diagnosed with any two of the following three factors, elevated TG (≥165 mg dL-1), TC (≥200 mg dL-1), NEFA (≥1.5 m Eq-1) levels and higher ALT activit (≥100 IU L-1) were diagnosed as MS. Presence of additional factors such as raised insulin levels (≥2.5 ng mL-1), confirmed the MS diagnosis. Based on these criteria, 13 (12.9%) of 101 dogs were diagnosed as MS. In these dogs, NEFA, TC and ALT levels were significantly higher than those in the control dogs (n = 88) without MS. MS was not detected in dogs with Body Condition Score (BCS)<3.
  Gebin Li , Peter Lee , Ichiro Yamamoto , Nobuko Mori and Toshiro Arai
  Peripheral Blood Leukocytes (PBL) continually interact with virtually every organ and tissue in the whole body. A remarkable concordance (80%) of gene expression profiles between peripheral blood mononuclear cells and different tissues has been previously demonstrated in humans. As such, gene expression responses of circulating PBL can therefore, potentially provide early warning of any abnormalities they discover. Weight alterations (increase or decrease) when associated with obesity has been reported to lead to alterations to PBL gene expression, especially those related to insulin and adiponectin signaling genes and even genes involved with energy homeostasis. As such, a pilot study involving PBL profiles of the following genes involved in energy homoestasis (5’ Adenosine Monophosphate-Activated Protein Kinase (AMPK)-α1 and 2, -β1 and 2 and -γ1 and 2); Glucose-6-Phosphate Dehydrogenase (G6PDH) and Malate Dehydrogenase (MDH), lipogenesis (Fatty Acid Synthase (FAS) and insulin signaling Adiponectin Receptor (ADIPOR) (-1 and 2); Insulin Receptor Substrates (IRS) (-1 and 2); Phosphatidylinositol-3 Kinase (PI3-K) were evaluated between lean and overweight dogs in an attempt to identify possible PBL biomarkers for assessing obesity in dogs. As compared to lean dogs, overweight dog PBL demonstrated reduced mRNA expression of IRS-1, IRS-2, FAS, G6PDH and AMPK β1 genes. Overall, these findings suggest that dysregulation of energy metabolism, associated with obesity in overweight dogs may carry over with alterations in PBL gene expression of genes involved in energy homeostasis and sterol metabolism. As such, PBL gene expression profiles may aid in early detection of PBL biomarkers for assessing obesity in dogs.
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