Teruyo Nakatani

National Institute of Health and Nutrition, Edo, Tōkyō, Japan

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Publications (6)22.85 Total impact

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    ABSTRACT: High-fish oil feeding and fasting down-regulate sterol regulatory element-binding protein-1c (SREBP-1c) mRNA level and suppress lipogenesis in mouse liver. Previous promoter analysis revealed that liver X receptor alpha (LXRalpha)/retinoid X receptor alpha (RXRalpha) complex was required for SREBP-1c gene expression in cell culture. In in vitro studies, polyunsaturated fatty acids (PUFAs, n-6, n-3) inhibited binding of LXRalpha/RXRalpha heterodimer to LXR responsive elements (LXREs) in the SREBP-1c promoter. To examine whether fish oil feeding and fasting would also inhibit its binding to LXREs in mouse liver, active liver nuclear extracts were prepared by percoll gradient centrifugation, and gel mobility shift assay was conducted. Although 1- to 5-day fish oil feeding and 2-day fasting decreased SREBP-1c mRNA by 45-68% and 65%, respectively, fish oil feeding decreased binding of LXR/RXR heterodimer to LXREs by 0-26%, while 2-day fasting decreased their binding by 40-56%. Luciferase assay using mutation of LXREs in mouse primary hepatocytes revealed that the LXR ligand, T0901317, induced increased transcription of SREBP-1c mRNA was mediated by LXREs, but it is unknown whether fish oil/eicosapentaenoic acid (EPA)-induced down-regulation of SREBP-1c mRNA was mediated by LXREs. These data indicate that high-fish oil feeding might decrease SREBP-1c mRNA partly by decreased transcription of SREBP-1c, but if so, the binding inhibition of LXRalpha to LXREs might not be a major cause, while fasting decreased SREBP-1c mRNA, mainly by its binding inhibition of LXRalpha to LXREs in the SREBP-1c promoter.
    Biochimica et Biophysica Acta 10/2005; 1736(1):77-86. · 4.66 Impact Factor
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    ABSTRACT: Body fat accumulation and bone loss are both often associated with estrogen deficiency following menopause. In this study, we examined whether soy isoflavone, one of the phytoestrogens, and moderate exercise interventions exhibit cooperative effects on body composition and bone mass in ovariectomized (OVX) mice. Eight-week-old female mice were assigned to 6 groups: (1) sham-operated (sham); (2) OVX; (3) OVX with received a soy isoflavone diet (OVX+ISO); (4) OVX with exercised on a treadmill (OVX+EX); (5) OVX with given both isoflavone and exercise (OVX+ISO&EX ); and (6) OVX with treated with 17 beta-estradiol subcutaneously (OVX+E2). Body composition and bone mineral density (BMD) were estimated by dual-energy x-ray absorptiometry (DXA). After the 6-week intervention, whole body fat (%) in the OVX group showed significantly higher than that in the sham group. Intervention of exercise and isoflavone alone partially inhibited OVX-induced body fat gain, and the combined intervention as well as E2 treatment completely restored fat mass to the sham level. Lean body mass in the whole body was not different in OVX group compared with that in OVX+ISO, OVX+EX, and OVX+E2 groups, but it was significantly higher in OVX+ISO&EX than in other groups. BMD of the whole body, lumbar spine, or femur showed significantly reduced by OVX, and the bone loss was partially inhibited by intervention of exercise or isoflavone alone. However, the combined intervention completely restored the bone mass to the level of sham, as did E2. Serum total cholesterol was significantly increased by OVX, which was normalized by the combined intervention or E2 treatment. These results demonstrate that combined intervention of soybean isoflavone and exercise prevented body fat accumulation in the whole body with an increase in lean body mass and restoration of bone mass, and reduced high serum cholesterol in OVX mice.
    Metabolism 07/2004; 53(7):942-8. · 3.10 Impact Factor
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    ABSTRACT: Rodents fed fish oil showed less obesity with a reduction of triglyceride synthesis in liver, relative to other dietary oils, along with a decrease of mature form of sterol regulatory element binding protein-1 (SREBP-1) and activation of peroxisome proliferator-activated receptor alpha (PPARalpha). Decrease of mature SREBP-1 protein by fish oil feeding was due to either inhibition of SREBP-1 proteolytic cascade or to decrease of its mRNA. To clarify its mechanism and relation to antiobesity effect, mice were fed fish oil in a range from 10 to 60 energy percent (en%). Fish oil feeding decreased body weight and fat mass in a dose-dependent manner, in parallel with PPARalpha activation and a decrease of SREBP-1 mRNA. However, compared with 0 en% fish oil feeding, 10 en% fish oil feeding decreased mature SREBP-1 protein by 50% with concomitant decreases of lipogenic genes, while precursor SREBP-1 protein rather increased by 1.3-fold. These data suggest that physiological doses of fish oil feeding effectively decrease expression of liver lipogenic enzymes by inhibiting SREBP-1 proteolytic cascade, while substantial decrease of SREBP-1 expression is observed in its pharmacological doses, and that activation of PPARalpha rather than SREBP-1 decrease might be related to the antiobesity effect of fish oil feeding.
    The Journal of Lipid Research 03/2003; 44(2):369-79. · 4.39 Impact Factor
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    ABSTRACT: Exercise increases utilization of lipids and carbohydrates in skeletal muscles. After exercise, replenishment of glycogen and triglyceride occurs in skeletal muscles. To elucidate the mechanism of lipid filling effect after exercise training, expression patterns of genes related to triglyceride synthesis were examined under several exercise conditions. Mice exercised by 2-week swimming had 1.4-2.0-fold increases of sterol regulatory element-binding protein 1 (SREBP-1) mRNA in skeletal muscles after the last swimming, with increases of lipogenic genes, such as acetyl-CoA carboxylase-1 (ACC-1), stearoyl-CoA desaturase-1 (SCD-1), and acyl CoA:diacylglycerol acyltransferase-1 (DGAT-1) mRNAs. An increase of SREBP-1 mRNA was observed after the 6-h treadmill running training but not after 1-h single treadmill running. Increase of SREBP-1 mRNA was due to the increase of SREBP-1c isoform but not of SREBP-1a. These data indicate that SREBP-1c, a key transcription factor of liver triglyceride synthesis, might also be responsible for skeletal muscle triglyceride synthesis after chronic exercise training.
    Biochemical and Biophysical Research Communications 09/2002; 296(2):395-400. · 2.41 Impact Factor
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    ABSTRACT: Peroxisome proliferator-activated receptor-alpha (PPARalpha)activators, fish oil feeding, or fibrate administration up-regulated mitochondrial uncoupling protein (UCP2) mRNA expression in mouse liver by 5-9-fold, whereas tumor necrosis factor-alpha (TNFalpha) also up-regulated UCP2 in liver. In this study, the mechanisms for PPARalpha activators-induced up-regulation of UCP2 mRNA, related to TNFalpha and reactive oxygen species (ROS), were investigated. PPARalpha activators-induced UCP2 up-regulation in mouse/rat liver tissues was due to their increases in hepatocytes but not in non-parenchymal cells. Addition of PPARalpha activators, WY14,643 or fenofibrate, to cultured hepatocytes up-regulated UCP2 mRNA by 5-10-fold. PPARalpha activators-induced up-regulation of UCP2 mRNA was not due to increased mRNA stability and required cycloheximide-sensitive short term turnover protein(s). However, expression of PPARalpha/retinoid X receptor-alpha and PGC-1 was not rate-limiting for WY14,643-induced UCP2 up-regulation. In primary hepatocytes, an exogenous oxidant, tert-butyl-hydroperoxide (TBHP), which increased ROS production, up-regulated UCP2 mRNA, whereas WY14,643 treatment did not produce detectable ROS under the condition that fibrate markedly up-regulated UCP2. In in vivo studies, PPARalpha activators moderately up-regulated TNFalpha mRNA expression in mouse liver. An anti-oxidant pyrrolidine dithiocarbamate ammonium salt injection completely prevented their TNFalpha mRNA increases but did not prevent most of their UCP2 mRNA increases. These data indicate that PPARalpha activators up-regulate UCP2 expression in hepatocytes through unknown proteins by increased transcription, and neither ROS nor TNFalpha production are the major causes for PPARalpha activators-induced UCP2 up-regulation.
    Journal of Biological Chemistry 04/2002; 277(11):9562-9. · 4.65 Impact Factor
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    ABSTRACT: Fish oil rich in n-3 polyunsaturated fatty acids has been shown to reduce the risk of cardiovascular diseases partly by reduction of blood triglyceride concentration. This favorable effect mainly results from the combined effects of inhibition of lipogenesis by decrease of SREBP-1 and stimulation of fatty acid oxidation by activation of peroxisome proliferator-activated receptor-alpha (PPARalpha) in liver. However, because fish oil is easily peroxidized to form hydroperoxides and increases oxidative stress, some defense mechanism(s) against oxidative stress might occur. To understand these complex effects of fish oil diet, the gene expression profile of mice liver was analyzed using high-density oligonucleotide arrays. High-fat diet (60% of total energy intake) as either safflower oil or fish oil (tuna) was given to mice. After 6 mo of feeding, expression levels of a total of 6,521 genes were analyzed. In fish oil diet compared with safflower oil diet, immune reaction-related genes, antioxidant genes (several glutathione transferases, uncoupling protein 2, and Mn-superoxide dismutase), and lipid catabolism-related genes upregulated, whereas cholesterol and fatty acid synthesis-related genes and 17-alpha hydroxylase/C17-20 lyase and sulfotransferases related to production of endogenous PPARalpha ligands and reactive oxygen species (ROS) downregulated markedly. Because upregulation of these antioxidant genes and downregulation of sulfotransferases were also observed in mice administered fenofibrate, altered gene expression related to antioxidant system observed in fish oil feeding was mediated directly and indirectly by PPARalpha activation. However, downregulation of 17-alpha hydroxylase/C17-20 lyase was not due to PPARalpha activation. These data indicate that fish oil feeding downregulated the endogenous PPARalpha-activation system and increased antioxidant gene expressions to protect against ROS excess.
    AJP Gastrointestinal and Liver Physiology 03/2002; 282(2):G338-48. · 3.65 Impact Factor