Metabolomic anatomy of an animal model revealing homeostatic imbalances in dyslipidaemia

Ooga, Takushi; Sato, Hajime; Nagashima, Atsushi; Sasaki, Kazunori; Tomita, Masaru; Soga, Tomoyoshi; Ohashi, Yoshiaki

doi:10.1039/c0mb00141d

Cited by 177 publications

(148 citation statements)

References 26 publications

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“…Lactate secretion was examined using a Lactate Assay Kit (BioVision). Isotopomer distribution analysis was performed by F-SCOPE package of Human Metabolome Technologies using capillary electrophoresis time-offlight mass spectrometry (14)(15)(16). Cells were incubated in DMEM with glucose replaced by 0.1% [U- …”

Section: Quantification Of Metabolitesmentioning

confidence: 99%

Decreased Expression of Fructose-1,6-bisphosphatase Associates with Glucose Metabolism and Tumor Progression in Hepatocellular Carcinoma

et al. 2016

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Fructose-1,6-bisphosphatase (FBP1), the rate-limiting enzyme in gluconeogenesis, is reduced in expression in certain cancers where it has been hypothesized to act as a tumor suppressor, including in hepatocellular carcinoma (HCC). Here, we report functional evidence supporting this hypothesis, providing a preclinical rationale to develop FBP1 as a therapeutic target for HCC treatment. Three independent cohorts totaling 594 cases of HCC were analyzed to address clinical significance. Lower FBP1 expression associated with advanced tumor stage, poor overall survival, and higher tumor recurrence rates. In HCC cell lines, where endogenous FBP1 expression is low, engineering its ectopic overexpression inhibited tumor growth and intracellular glucose uptake by reducing aerobic glycolysis. In patient specimens, promoter methylation and copy-number loss of FBP1 were independently associated with decreased FBP1 expression. Similarly, FBP1 downregulation in HCC cell lines was also associated with copy-number loss. HCC specimens exhibiting low expression of FBP1 had a highly malignant phenotype, including large tumor size, poor differentiation, impaired gluconeogenesis, and enhanced aerobic glycolysis. The effects of FBP1 expression on prognosis and glucose metabolism were confirmed by gene set enrichment analysis. Overall, our findings established that FBP1 downregulation in HCC contributed to tumor progression and poor prognosis by altering glucose metabolism, and they rationalize further study of FBP1 as a prognostic biomarker and therapeutic target in HCC patients. Cancer Res; 76(11); 3265-76. Ó2016 AACR.

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Section: Quantification Of Metabolitesmentioning

confidence: 99%

Decreased Expression of Fructose-1,6-bisphosphatase Associates with Glucose Metabolism and Tumor Progression in Hepatocellular Carcinoma

et al. 2016

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“…Bioluminescence imaging was performed as previously described in Ooga, et al [8]. In brief, mice were anesthetized, injected intraperitoneally with D-luciferin sodium salt 5 minutes before beginning photon recording.…”

Section: Bioluminescence Imagingmentioning

confidence: 99%

Food Additive P-80 Impacts Mouse Gut Microbiota Promoting Intestinal Inflammation, Obesity and Liver Dysfunction

Singh¹

2016

SOJMID

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Open Access Research Articlethe globalization of unhealthy lifestyle. Key metabolic and physiological changes, including obesity, metabolic syndrome and Nonalcoholic Fatty Liver Disease (NAFLD) are commonly associated with chronic, non-communicable disease that are responsible for approximately 70% of the world's death.There are compelling arguments to include the composition of gut microbiota as a key risk factor for the development of obesity and obesity related metabolic disorders, including insulin resistance, type 2 diabetes, dyslipidemia and non-alcoholic fatty liver disease [3]. The gut microbiota has been implicated in having both direct (i.e. through effect on nutrient uptake) and indirect effect on health [4,5]. In mice, food additives have been demonstrated to affect the host microbiota interaction, leading to low-grade inflammation, adiposity and adiposity associated metabolic effect [6].We set out to elucidate whether alteration in the gut microbial community after P-80 ingestion is a causative agent of liver dysfunction. To explore this possibility, we setup an experiment to examine the impact of P-80 on gut microbiota using wild-type C57BL/ 6 mice. The experimental mice were gavaged with the amount of P-80 equal to 1% of their body weight. This amount correlates to the acceptable daily human intake of 1% per kg of polysorbate-80 to body weight [7]. Methods Mice and dietThe C57BL/6 (000664) mice were purchased from The Jackson Laboratory. The mice were maintained under specific pathogenfree conditions, on a 12-h light-dark cycle, and fed normal diet (12 kcal% fat, 29 kcal% protein, 59% kcal carbohydrate) ad libitum. For this study there were two groups: one control group (ingesting saline via gavage) and one experimental P-80 fed group (ingesting P-80 dissolve in saline, 1% per kg via gavage). This dose corresponds to the FDA Acceptable Daily Intake (ADI) in humans (1% per kg (body weight), adjusted to the mouse AbstractThe increasing prevalence of obesity has emerged as one of the most important global public health issue. The change to the human microbiome as a result of changes in the quality and quantity of food intake over the past several decades has been implicated in the development of obesity and metabolic syndrome. We administered polysorbate-80 to mice via gavage. The researchers monitor liver noninvasively using a bioluminescence imaging. For the liver dysfunction we measure the liver enzymes and PAS stain on liver, electron microscopy liver mitochondria. For the assessment of intestinal inflammation we measured fecal LCN2, LPS, MPO and flagellin by ELISA and qPCR. We use confocal microscopy to detect closet bacteria near the epithelium. 16S sequence was used for the composition of microbiota. Compared with control mice, those receiving emulsifier, showed impaired glycemic tolerance, hyperinsulinemia, altered liver enzymes, larger mitochondria and increased gall bladder size. Additionally, mice in the experimental group showed higher levels of DCA, reduced Muc2 RNA expression, reduced m...

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“…The spectrometer was scanned from m/z 50 to 1000. 10,11 Peaks were extracted using MasterHands automatic integration software 12 and MassHunter Quantitative Analysis B.04.00 (Agilent Technologies) to obtain peak information, including m/z, peak area, and migration time (MT). Signal peaks were annotated according to the HMT metabolite database on the basis of their m/z values with the MTs.…”

Section: Metabolite Extraction and Metabolome Analysismentioning

confidence: 99%

Setdb1 maintains hematopoietic stem and progenitor cells by restricting the ectopic activation of nonhematopoietic genes

Koide

Oshima

Takubo

et al. 2016

Blood

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Metabolomic anatomy of an animal model revealing homeostatic imbalances in dyslipidaemia

Cited by 177 publications

References 26 publications

Decreased Expression of Fructose-1,6-bisphosphatase Associates with Glucose Metabolism and Tumor Progression in Hepatocellular Carcinoma

Decreased Expression of Fructose-1,6-bisphosphatase Associates with Glucose Metabolism and Tumor Progression in Hepatocellular Carcinoma

Food Additive P-80 Impacts Mouse Gut Microbiota Promoting Intestinal Inflammation, Obesity and Liver Dysfunction

Setdb1 maintains hematopoietic stem and progenitor cells by restricting the ectopic activation of nonhematopoietic genes

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