RESUMEN
Metabolic syndrome comprises a cluster of metabolic disorders related to the development of cardiovascular disease and type 2 diabetes mellitus. In latter years, plant secondary metabolites have become of special interest because of their potential role in preventing and managing metabolic syndrome. Sesquiterpene lactones constitute a large and diverse group of biologically active compounds widely distributed in several medicinal plants used for the treatment of metabolic disorders. The structural diversity and the broad spectrum of biological activities of these compounds drew significant interests in the pharmacological applications. This review describes selected sesquiterpene lactones that have been experimentally validated for their biological activities related to risk factors of metabolic syndrome, together with their mechanisms of action. The potential beneficial effects of sesquiterpene lactones discussed in this review demonstrate that these substances represent remarkable compounds with a diversity of molecular structure and high biological activity, providing new insights into the possible role in metabolic syndrome management.
RESUMEN
BACKGROUND: Hexokinase and glucokinase enzymes are ubiquitously expressed and use ATP and ADP as substrates in mammalian systems and a variety of polyphosphate substrates and/or ATP in some eukaryotic and microbial systems. Polyphosphate synthesising or utilizing enzymes are widely expressed in microbial systems but have not been reported in mammalian systems, despite the presence of polyphosphate in mammalian cells. Only two micro-organisms have previously been shown to express an enzyme that uses polyphosphate exclusively. METHODS: A variety of experimental approaches, including NMR and NAD-linked assay systems were used to conduct a biochemical investigation of polyphosphate dependent glucokinase activity in mammalian tissues. RESULTS: A novel mammalian glucokinase, highly responsive to hexametaphosphate (HMP) but not ATP or ADP as a phosphoryl donor is present in the nuclei of mammalian hepatocytes. The liver enzyme exhibited sigmoidal kinetics with respect to glucose with a S0.5 of 12 mM, similar to the known kinetics of mammalian ATP-glucokinase. The Km for HMP (0.5 mM) was also similar to that of phosphoryl donors for mammalian ATP-glucokinases. The new enzyme was inhibited by several nucleotide phosphates. CONCLUSIONS: We report the discovery of a polyphosphate-dependent enzyme system in mammalian cells with kinetics similar to established ATP-dependent glucokinase, also known to have a nuclear location. The kinetics suggest possible regulatory or redox protective roles. GENERAL SIGNIFICANCE: The role of polyphosphate in mammalian systems has remained an enigma for decades, and the present report describes progress on the significance of this compound in intracellular metabolism in mammals.
RESUMEN
Four isolipidic and isoenergetic diets with different protein:carbohydrate (CH) contents (48:38, 52:34, 56:30, 60:26) were fed to juvenile Senegalese sole (22·01 (sem 0·01) g) during 104 d. Oral glucose tolerance tests were performed at the beginning (4 d) and at the end (104 d) of the experiment to assess the effect of the dietary treatment on glucose tolerance. Samples of blood, liver and muscle of all dietary groups were also obtained at the initial and final phases of the trial at different postprandial times (0, 1, 5 and 10 h after feeding) in order to analyse glucose and NEFA in plasma, and metabolites and enzyme activities involved in glycogen metabolism, glycolysis, gluconeogenesis and lipogenesis pathways in liver and muscle. The results obtained in this study suggest a good glucose tolerance in Senegalese sole. This species tolerated important amounts of CH in the diet without showing any deleterious signs in terms of growth or any metabolic disorders. After 104 d of feeding diets with an important amount of CH (48:38 and 52:34), the control of glycaemia was maintained and even postprandial glucose levels in plasma were (in general) lower than at the beginning of the experiment. This reasonable tolerance to glucose is also reflected by an increased use of glucose through glycolysis in liver (indicated by glucokinase activity), and the absence of changes in lipogenic potential in the same tissue (indicated by ATP citrate lyase activity). No clear changes were induced in the muscle by the dietary treatments.
Asunto(s)
Dieta , Carbohidratos de la Dieta/administración & dosificación , Proteínas en la Dieta/administración & dosificación , Peces Planos/metabolismo , Glucosa/metabolismo , Metabolismo de los Lípidos , Hígado/metabolismo , ATP Citrato (pro-S)-Liasa/metabolismo , Alimentación Animal , Fenómenos Fisiológicos Nutricionales de los Animales , Animales , Acuicultura , Glucemia/metabolismo , Carbohidratos de la Dieta/metabolismo , Carbohidratos de la Dieta/farmacología , Ingestión de Energía , Ácidos Grasos no Esterificados/sangre , Glucoquinasa/metabolismo , Glucógeno/metabolismo , Glucólisis , Hiperglucemia/etiología , Músculos/metabolismo , Periodo PosprandialRESUMEN
Plant feedstuffs (PF) are rich in carbohydrates, which may interact with lipid metabolism. Thus, when considering dietary replacement of fishery by-products with PF, knowledge is needed on how dietary lipid source (LS) and carbohydrates affect lipid metabolism and other metabolic pathways. For that purpose, a 73-d growth trial was performed with European sea bass juveniles (IBW 74 g) fed four diets differing in LS (fish oil (FO) or a blend of vegetable oils (VO)) and carbohydrate content (0 % (CH-) or 20 % (CH+) gelatinised starch). At the end of the trial no differences among diets were observed on growth and feed utilisation. Protein efficiency ratio was, however, higher in the CH+ groups. Muscle and liver fatty acid profiles reflected the dietary LS. Dietary carbohydrate promoted higher plasma cholesterol and phospholipids (PL), whole-body and hepatic (mainly 16 : 0) lipids and increased muscular and hepatic glycogen. Except for PL, which were higher in the FO groups, no major alterations between FO and VO groups were observed on plasma metabolites (glucose, TAG, cholesterol, PL), liver and muscle glycogen, and lipid and cholesterol contents. Activities of glucose-6-phosphate dehydrogenase and malic enzyme - lipogenesis-related enzymes - increased with carbohydrate intake. Hepatic expression of genes involved in cholesterol metabolism was up-regulated with carbohydrate (HMGCR and CYP3A27) and VO (HMGCR and CYP51A1) intake. No dietary regulation of long-chain PUFA biosynthesis at the transcriptional level was observed. Overall, very few interactions between dietary carbohydrates and LS were observed. However, important insights on the direct relation between dietary carbohydrate and the cholesterol biosynthetic pathway in European sea bass were demonstrated.
Asunto(s)
Lubina/metabolismo , Colesterol/sangre , Dieta/veterinaria , Carbohidratos de la Dieta/administración & dosificación , Grasas de la Dieta/administración & dosificación , Metabolismo de los Lípidos , Alimentación Animal , Animales , Glucemia/metabolismo , Ácido Graso Desaturasas/genética , Ácido Graso Desaturasas/metabolismo , Aceites de Pescado/administración & dosificación , Glucoquinasa/genética , Glucoquinasa/metabolismo , Glucosafosfato Deshidrogenasa/genética , Glucosafosfato Deshidrogenasa/metabolismo , Hígado/metabolismo , Músculo Esquelético/metabolismo , Fosfoenolpiruvato Carboxiquinasa (GTP)/genética , Fosfoenolpiruvato Carboxiquinasa (GTP)/metabolismo , Aceites de Plantas/administración & dosificación , Piruvato Quinasa/genética , Piruvato Quinasa/metabolismo , ARN Mensajero/genética , ARN Mensajero/metabolismo , Almidón/administración & dosificación , Almidón/química , Triglicéridos/sangre , Regulación hacia ArribaRESUMEN
It has recently been proposed that hypothalamic glial cells sense glucose levels and release lactate as a signal to activate adjacent neurons. GK (glucokinase), the hexokinase involved in glucose sensing in pancreatic beta-cells, is also expressed in the hypothalamus. However, it has not been clearly determined if glial and/or neuronal cells express this protein. Interestingly, tanycytes, the glia that cover the ventricular walls of the hypothalamus, are in contact with CSF (cerebrospinal fluid), the capillaries of the arcuate nucleus and adjacent neurons; this would be expected for a system that can detect and communicate changes in glucose concentration. Here, we demonstrated by Western-blot analysis, QRT-PCR [quantitative RT-PCR (reverse transcription-PCR)] and in situ hybridization that GK is expressed in tanycytes. Confocal microscopy and immuno-ultrastructural analysis revealed that GK is localized in the nucleus and cytoplasm of beta1-tanycytes. Furthermore, GK expression increased in these cells during the second week of post-natal development. Based on this evidence, we propose that tanycytes mediate, at least in part, the mechanism by which the hypothalamus detects changes in glucose concentrations.