Modulation of the cellular content of metabolites in adipocytes by insulin

Qiao, Yuhang; Tomonaga, Shozo; Matsui, Tohru; Funaba, Masayuki

doi:10.1016/j.mce.2016.01.017

Cited by 9 publications

(14 citation statements)

References 45 publications

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“…Metabolomic analysis was performed by gas chromatography mass spectrometry as previously described, with some modifications. The metabolites were identified by the method of Lai et al The peak height of each metabolite was measured, and the cellular level of the metabolite was calculated by dividing the peak height of the metabolite by that of 2‐isopropylmalic acid, an internal standard, and the soluble protein content.…”

Section: Methodsmentioning

confidence: 99%

“…The pathways affected by ATRA were detected using MetaboAnalyst; metabolites that were significantly different between control cells and ATRA‐treated cells were subjected to an enrichment analysis (http://www.metaboanalyst.ca/faces/docs/Tutorial.xhtml, accessed June 2018). To visualize the changes in the cellular metabolite levels in response to ATRA treatment, a heat map was prepared and hierarchical cluster analysis was performed, as previously described . The threshold for grouping was set to a correlation coefficient of 0.85 in the dendrogram, and the dendrogram was grouped to have as few clusters as possible.…”

Section: Methodsmentioning

confidence: 99%

“…Metabolomic analysis was performed by gas chromatography mass spectrometry as previously described, 21,22 with some modifications.…”

Section: Metabolomic Analysismentioning

confidence: 99%

“…To visualize the changes in the cellular metabolite levels in response to ATRA treatment, a heat map was prepared and hierarchical cluster analysis was performed, as previously described. 21,22 The threshold for grouping was set to a correlation coefficient of 0.85 in the dendrogram, and the dendrogram was grouped to have as few clusters as possible.…”

Section: Metabolomic Analysismentioning

confidence: 99%

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Chronic retinoic acid treatment induces differentiation and changes in the metabolite levels of brown (pre)adipocytes

Suzuki

Chen

Tomonaga

et al. 2019

Cell Biochemistry & Function

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Dietary vitamin A status affects energy metabolism. The present study explored the effect of all‐trans retinoic acid (ATRA) on the expression levels of molecules and metabolites of brown adipocytes. Chronic ATRA treatment was initiated during the early stage (days 0‐8) or late stage (days 8‐12) of adipogenesis. Treatment with ATRA during the early and late stage of adipogenesis resulted in an increase in the expression level of Ucp1 and Cidea, genes highly expressed in brown adipocytes, on day 8 and day 12, respectively, whereas expression of Pgc‐1α, another gene expressed during brown adipogenesis, was unaffected by ATRA. Non‐targeted metabolomic analyses indicated that the pathways related to the glucose metabolism were affected by ATRA, irrespective of the differentiation stage. Cellular levels of glucose 6‐phosphate, fructose 6‐phosphate, citric acid, and succinic acid decreased after ATRA treatment on days 8 and 12. In contrast, glucose level was higher in ATRA‐treated cells on day 8, but it was lower on day 12. ATRA decreased the cellular level of aconitic acid, fumaric acid, and malic acid on day 12 but not on day 8. Furthermore, ATRA increased the expression level of Hxk2 and downregulated the expressions of G6pdh and Pfkl/Pfkp on day 8 but not on day 12. Together, the results indicate that the chronic treatment with ATRA stimulated the formation of activated brown adipocytes, eventually leading to alterations in the levels of cellular metabolites related to glucose metabolism. Significance of the study Significance of the study treatment with all‐trans retinoic acid (ATRA) during the early and late stage of adipogenesis increased the expression of Ucp1 and Cidea, genes highly expressed in brown adipocytes, on day 8 and day 12. Cellular levels of glucose 6‐phosphate, fructose 6‐phosphate, citric acid, and succinic acid decreased after ATRA treatment on days 8 and 12. In contrast, glucose level was higher in ATRA‐treated cells on day 8, but it was lower on day 12. The present results indicate that ATRA stimulated the formation of activated brown adipocytes, eventually leading to alterations in the levels of cellular metabolites related to glucose metabolism.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

“…Metabolomic analysis was performed by gas chromatography mass spectrometry as previously described, 21,22 with some modifications.…”

Section: Metabolomic Analysismentioning

confidence: 99%

Section: Metabolomic Analysismentioning

confidence: 99%

See 2 more Smart Citations

Chronic retinoic acid treatment induces differentiation and changes in the metabolite levels of brown (pre)adipocytes

Suzuki

Chen

Tomonaga

et al. 2019

Cell Biochemistry & Function

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“…Next, 160 μl of the supernatant was mixed with 200 μl of distilled water and vortexed, followed by centrifugation at 16 000 g at 4°C for 5 min; subsequently, 250 μl of the supernatant was dried under a vacuum using a centrifugal evaporator (RD-400; Yamato Scientific). Dried samples were pre-treated, derivatised and analysed by GC/MS (GCMS QP2010-Ultra; Shimadzu) within 24 h of derivatisation as described by Qiao et al (15) . The Shimadzu Smart Metabolites Database (Shimadzu) was used to identify metabolites.…”

Section: Metabolomic Analysismentioning

confidence: 99%

Fluctuations in metabolite content in the liver of magnesium-deficient rats

et al. 2016

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Mg deficiency induces various metabolic disturbances including glucose metabolism in the liver. However, no comprehensive information is currently available on the metabolic pathways affected by Mg deficiency. The present study examined metabolite content in the liver of Mg-deficient rats using a metabolomic analysis. In this study, 4-week-old, male Sprague-Dawley rats were fed a control diet or a Mg-deficient diet for 8 weeks. The metabolomic analysis identified 105 metabolites in the liver, and significant differences were observed in the hepatic contents for thirty-three metabolites between the two groups. An analysis by MetaboAnalyst, a web-based metabolome data analysis tool, indicated that the Mg deficiency affected taurine/hypotaurine metabolism, methionine metabolism and glycine/serine/threonine metabolism; taurine, hypotaurine, glycine, serine and threonine contents were increased by Mg deficiency, whereas the amounts of 2-ketobutyric acid (a metabolite produced by the catabolism of cystathionine or threonine) and 5'-methylthioadenosine (a metabolite involved in spermidine synthesis) were decreased. The amount of glucose 6-phosphate, a hub metabolite of glycolysis/gluconeogenesis and the pentose phosphate pathway, was significantly decreased in Mg-deficient rats. Mg deficiency also decreased metabolite contents from the citric acid cycle, including citric acid, fumaric acid and malic acid. Aberrant metabolism may be related to the allosteric regulation of enzymes; the mRNA levels of enzymes were generally similar between the two groups. The present study suggests that the Mg deficiency-mediated modulation of hepatic metabolism is as yet uncharacterised.

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Metabolic changes in adipose tissues in response to β₃‐adrenergic receptor activation in mice

Fujimoto

Hashimoto

Shindo

et al. 2018

J of Cellular Biochemistry

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Brown and beige adipocytes dissipate energy as heat. Thus, the activation of brown adipocytes and the emergence of beige adipocytes in white adipose tissue (WAT) are suggested to be useful for preventing and treating obesity. Although β -adrenergic receptor activation is known to stimulate lipolysis and activation of brown and beige adipocytes, fat depot-dependent changes in metabolite concentrations are not fully elucidated. The current study examined the effect of treatment with CL-316,243, a β -adrenergic receptor agonist, on the relative abundance of metabolites in interscapular brown adipose tissue (iBAT), inguinal WAT (ingWAT), and epididymal WAT (epiWAT). Intraperitoneal injection of CL-316,243 (1 mg/kg) for 3 consecutive days increased the relative abundance of several glycolysis-related metabolites in all examined fat depots. The cellular concentrations of metabolites involved in the citric acid cycle and of free amino acids were also increased in epiWAT by CL-316,243. CL-316,243 increased the expression levels of several enzymes and transporters related to glucose metabolism and amino acid catabolism in ingWAT and iBAT but not in epiWAT. CL-316,243 also induced the emergence of more beige adipocytes in ingWAT than in epiWAT. Furthermore, adipocytes surrounded by macrophages were detected in the epiWAT of mice given CL-316,243. The current study reveals the fat depot-dependent modulation of cellular metabolites in CL-316,243-treated mice, presumably resulting from differential regulation of cell metabolism in different cell populations.

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Modulation of the cellular content of metabolites in adipocytes by insulin

Cited by 9 publications

References 45 publications

Chronic retinoic acid treatment induces differentiation and changes in the metabolite levels of brown (pre)adipocytes

Chronic retinoic acid treatment induces differentiation and changes in the metabolite levels of brown (pre)adipocytes

Fluctuations in metabolite content in the liver of magnesium-deficient rats

Metabolic changes in adipose tissues in response to β₃‐adrenergic receptor activation in mice

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Modulation of the cellular content of metabolites in adipocytes by insulin

Cited by 9 publications

References 45 publications

Chronic retinoic acid treatment induces differentiation and changes in the metabolite levels of brown (pre)adipocytes

Chronic retinoic acid treatment induces differentiation and changes in the metabolite levels of brown (pre)adipocytes

Fluctuations in metabolite content in the liver of magnesium-deficient rats

Metabolic changes in adipose tissues in response to β3‐adrenergic receptor activation in mice

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Metabolic changes in adipose tissues in response to β₃‐adrenergic receptor activation in mice