Systemic oscillator-driven and nutrient-responsive hormonal regulation of daily expression rhythms for gluconeogenic enzyme genes in the mouse liver

Akiko Taira, Emiko Arita, Eriko Matsumoto, Ayano Oohira, Katsuro Iwase, Takaki Hiwasa, Koutaro Yokote, Shigenobu Shibata, Masaki Takiguchi

    研究成果: Article

    抄録

    Gluconeogenesis is de novo glucose synthesis from substrates such as amino acids and is vital when glucose is lacking in the diurnal nutritional fluctuation. Accordingly, genes for hepatic gluconeogenic enzymes exhibit daily expression rhythms, whose detailed regulations under nutritional variations remain elusive. As a first step, we performed general systematic characterization of daily expression profiles of gluconeogenic enzyme genes for phosphoenolpyruvate carboxykinase (PEPCK), cytosolic form (Pck1), glucose-6-phosphatase (G6Pase), catalytic subunit (G6pc), and tyrosine aminotransferase (TAT) (Tat) in the mouse liver. On a standard diet fed ad libitum, mRNA levels of these genes showed robust daily rhythms with a peak or an elevation phase during the late sleep-fasting period in the diurnal feeding/fasting (wake/sleep) cycle. The rhythmicity was preserved in constant darkness, modulated with prolonged fasting, attenuated by Clock mutation, and entrained to varied photoperiods and time-restricted feedings. These results are concordant with the notion that gluconeogenic enzyme genes are under the control of the intrinsic circadian oscillator, which is entrained by the light/dark cycle, and which in turn entrains the feeding/fasting cycle and also drives systemic signaling pathways such as the hypothalamic-pituitary-adrenal axis. On the other hand, time-restricted feedings also showed that the ingestion schedule, when separated from the light/dark cycle, can serve as an independent entrainer to daily expression rhythms of gluconeogenic enzyme genes. Moreover, nutritional changes dramatically modified expression profiles of the genes. In addition to prolonged fasting, a high-fat diet and a high-carbohydrate (no-protein) diet caused modification of daily expression rhythms of the genes, with characteristic changes in profiles of glucoregulatory hormones such as corticosterone, glucagon, and insulin, as well as their modulators including ghrelin, leptin, resistin, glucose-dependent insulinotropic polypeptide (GIP), and glucagon-like peptide-1 (GLP-1). Remarkably, high-protein (60% casein or soy-protein) diets activated the gluconeogenic enzyme genes atypically during the wake-feeding period, with paradoxical up-regulation of glucagon, which frequently formed correlation networks with other humoral factors. Based on these results, we propose that daily expression rhythms of gluconeogenic enzyme genes are under the control of systemic oscillator-driven and nutrient-responsive hormones.

    元の言語English
    ジャーナルChronobiology International
    DOI
    出版物ステータスPublished - 2019 1 1

    Fingerprint

    Food
    Fasting
    Liver
    Enzymes
    Photoperiod
    Genes
    Glucagon
    Glucose
    Sleep
    Hormones
    Tyrosine Transaminase
    Diet
    Resistin
    Diet Therapy
    Glucose-6-Phosphatase
    Phosphoenolpyruvate
    Soybean Proteins
    Ghrelin
    Glucagon-Like Peptide 1
    Gluconeogenesis

    ASJC Scopus subject areas

    • Physiology
    • Physiology (medical)

    これを引用

    Systemic oscillator-driven and nutrient-responsive hormonal regulation of daily expression rhythms for gluconeogenic enzyme genes in the mouse liver. / Taira, Akiko; Arita, Emiko; Matsumoto, Eriko; Oohira, Ayano; Iwase, Katsuro; Hiwasa, Takaki; Yokote, Koutaro; Shibata, Shigenobu; Takiguchi, Masaki.

    :: Chronobiology International, 01.01.2019.

    研究成果: Article

    Taira, Akiko ; Arita, Emiko ; Matsumoto, Eriko ; Oohira, Ayano ; Iwase, Katsuro ; Hiwasa, Takaki ; Yokote, Koutaro ; Shibata, Shigenobu ; Takiguchi, Masaki. / Systemic oscillator-driven and nutrient-responsive hormonal regulation of daily expression rhythms for gluconeogenic enzyme genes in the mouse liver. :: Chronobiology International. 2019.
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    abstract = "Gluconeogenesis is de novo glucose synthesis from substrates such as amino acids and is vital when glucose is lacking in the diurnal nutritional fluctuation. Accordingly, genes for hepatic gluconeogenic enzymes exhibit daily expression rhythms, whose detailed regulations under nutritional variations remain elusive. As a first step, we performed general systematic characterization of daily expression profiles of gluconeogenic enzyme genes for phosphoenolpyruvate carboxykinase (PEPCK), cytosolic form (Pck1), glucose-6-phosphatase (G6Pase), catalytic subunit (G6pc), and tyrosine aminotransferase (TAT) (Tat) in the mouse liver. On a standard diet fed ad libitum, mRNA levels of these genes showed robust daily rhythms with a peak or an elevation phase during the late sleep-fasting period in the diurnal feeding/fasting (wake/sleep) cycle. The rhythmicity was preserved in constant darkness, modulated with prolonged fasting, attenuated by Clock mutation, and entrained to varied photoperiods and time-restricted feedings. These results are concordant with the notion that gluconeogenic enzyme genes are under the control of the intrinsic circadian oscillator, which is entrained by the light/dark cycle, and which in turn entrains the feeding/fasting cycle and also drives systemic signaling pathways such as the hypothalamic-pituitary-adrenal axis. On the other hand, time-restricted feedings also showed that the ingestion schedule, when separated from the light/dark cycle, can serve as an independent entrainer to daily expression rhythms of gluconeogenic enzyme genes. Moreover, nutritional changes dramatically modified expression profiles of the genes. In addition to prolonged fasting, a high-fat diet and a high-carbohydrate (no-protein) diet caused modification of daily expression rhythms of the genes, with characteristic changes in profiles of glucoregulatory hormones such as corticosterone, glucagon, and insulin, as well as their modulators including ghrelin, leptin, resistin, glucose-dependent insulinotropic polypeptide (GIP), and glucagon-like peptide-1 (GLP-1). Remarkably, high-protein (60{\%} casein or soy-protein) diets activated the gluconeogenic enzyme genes atypically during the wake-feeding period, with paradoxical up-regulation of glucagon, which frequently formed correlation networks with other humoral factors. Based on these results, we propose that daily expression rhythms of gluconeogenic enzyme genes are under the control of systemic oscillator-driven and nutrient-responsive hormones.",
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    T1 - Systemic oscillator-driven and nutrient-responsive hormonal regulation of daily expression rhythms for gluconeogenic enzyme genes in the mouse liver

    AU - Taira, Akiko

    AU - Arita, Emiko

    AU - Matsumoto, Eriko

    AU - Oohira, Ayano

    AU - Iwase, Katsuro

    AU - Hiwasa, Takaki

    AU - Yokote, Koutaro

    AU - Shibata, Shigenobu

    AU - Takiguchi, Masaki

    PY - 2019/1/1

    Y1 - 2019/1/1

    N2 - Gluconeogenesis is de novo glucose synthesis from substrates such as amino acids and is vital when glucose is lacking in the diurnal nutritional fluctuation. Accordingly, genes for hepatic gluconeogenic enzymes exhibit daily expression rhythms, whose detailed regulations under nutritional variations remain elusive. As a first step, we performed general systematic characterization of daily expression profiles of gluconeogenic enzyme genes for phosphoenolpyruvate carboxykinase (PEPCK), cytosolic form (Pck1), glucose-6-phosphatase (G6Pase), catalytic subunit (G6pc), and tyrosine aminotransferase (TAT) (Tat) in the mouse liver. On a standard diet fed ad libitum, mRNA levels of these genes showed robust daily rhythms with a peak or an elevation phase during the late sleep-fasting period in the diurnal feeding/fasting (wake/sleep) cycle. The rhythmicity was preserved in constant darkness, modulated with prolonged fasting, attenuated by Clock mutation, and entrained to varied photoperiods and time-restricted feedings. These results are concordant with the notion that gluconeogenic enzyme genes are under the control of the intrinsic circadian oscillator, which is entrained by the light/dark cycle, and which in turn entrains the feeding/fasting cycle and also drives systemic signaling pathways such as the hypothalamic-pituitary-adrenal axis. On the other hand, time-restricted feedings also showed that the ingestion schedule, when separated from the light/dark cycle, can serve as an independent entrainer to daily expression rhythms of gluconeogenic enzyme genes. Moreover, nutritional changes dramatically modified expression profiles of the genes. In addition to prolonged fasting, a high-fat diet and a high-carbohydrate (no-protein) diet caused modification of daily expression rhythms of the genes, with characteristic changes in profiles of glucoregulatory hormones such as corticosterone, glucagon, and insulin, as well as their modulators including ghrelin, leptin, resistin, glucose-dependent insulinotropic polypeptide (GIP), and glucagon-like peptide-1 (GLP-1). Remarkably, high-protein (60% casein or soy-protein) diets activated the gluconeogenic enzyme genes atypically during the wake-feeding period, with paradoxical up-regulation of glucagon, which frequently formed correlation networks with other humoral factors. Based on these results, we propose that daily expression rhythms of gluconeogenic enzyme genes are under the control of systemic oscillator-driven and nutrient-responsive hormones.

    AB - Gluconeogenesis is de novo glucose synthesis from substrates such as amino acids and is vital when glucose is lacking in the diurnal nutritional fluctuation. Accordingly, genes for hepatic gluconeogenic enzymes exhibit daily expression rhythms, whose detailed regulations under nutritional variations remain elusive. As a first step, we performed general systematic characterization of daily expression profiles of gluconeogenic enzyme genes for phosphoenolpyruvate carboxykinase (PEPCK), cytosolic form (Pck1), glucose-6-phosphatase (G6Pase), catalytic subunit (G6pc), and tyrosine aminotransferase (TAT) (Tat) in the mouse liver. On a standard diet fed ad libitum, mRNA levels of these genes showed robust daily rhythms with a peak or an elevation phase during the late sleep-fasting period in the diurnal feeding/fasting (wake/sleep) cycle. The rhythmicity was preserved in constant darkness, modulated with prolonged fasting, attenuated by Clock mutation, and entrained to varied photoperiods and time-restricted feedings. These results are concordant with the notion that gluconeogenic enzyme genes are under the control of the intrinsic circadian oscillator, which is entrained by the light/dark cycle, and which in turn entrains the feeding/fasting cycle and also drives systemic signaling pathways such as the hypothalamic-pituitary-adrenal axis. On the other hand, time-restricted feedings also showed that the ingestion schedule, when separated from the light/dark cycle, can serve as an independent entrainer to daily expression rhythms of gluconeogenic enzyme genes. Moreover, nutritional changes dramatically modified expression profiles of the genes. In addition to prolonged fasting, a high-fat diet and a high-carbohydrate (no-protein) diet caused modification of daily expression rhythms of the genes, with characteristic changes in profiles of glucoregulatory hormones such as corticosterone, glucagon, and insulin, as well as their modulators including ghrelin, leptin, resistin, glucose-dependent insulinotropic polypeptide (GIP), and glucagon-like peptide-1 (GLP-1). Remarkably, high-protein (60% casein or soy-protein) diets activated the gluconeogenic enzyme genes atypically during the wake-feeding period, with paradoxical up-regulation of glucagon, which frequently formed correlation networks with other humoral factors. Based on these results, we propose that daily expression rhythms of gluconeogenic enzyme genes are under the control of systemic oscillator-driven and nutrient-responsive hormones.

    KW - blood glucose

    KW - Circadian rhythm

    KW - clock genes

    KW - hyperglycemia

    KW - hypoglycemia

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