Dynamic Metabolome Analysis Reveals the Metabolic Fate of Medium-Chain Fatty Acids in AML12 Cells

Fushimi, Tatsuya; Izumi, Yoshihiro; Takahashi, Masatomo; Hata, Kunihiko; Murano, Yoshihiro; Bamba, Takeshi

doi:10.1021/acs.jafc.0c04723

Cited by 34 publications

(42 citation statements)

References 68 publications

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“…organic acids, nucleotides, etc.) [ 70 , 71 ] and a liquid chromatography with a Discovery HS F5 column (2.1 mm i.d. 150 mm, 3 µm particle size, Merck, Darmstadt, Germany) coupled with a quadrupole-Orbitrap mass spectrometry (PFPP-LC/MS) (Thermo Fisher Scientific) for cationic polar metabolites (i.e.…”

Section: Methodsmentioning

confidence: 99%

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Differential effect of canagliflozin, a sodium–glucose cotransporter 2 (SGLT2) inhibitor, on slow and fast skeletal muscles from nondiabetic mice

Otsuka

Yokomizo

Nakamura

et al. 2022

Biochemical Journal

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There has been a concern that sodium-glucose cotransporter 2 (SGLT2) inhibitors could reduce skeletal muscle mass and function. Here, we examine the effect of canagliflozin (CANA), an SGLT2 inhibitor, on slow and fast muscles from nondiabetic C57BL/6J mice. In this study, mice were fed with or without CANA under ad libitum feeding, and then evaluated for metabolic valuables as well as slow and fast muscle mass and function. We also examined the effect of CANA on gene expressions and metabolites in slow and fast muscles. During SGLT2 inhibition, fast muscle function is increased, as accompanied by increased food intake, whereas slow muscle function is unaffected, although slow and fast muscle mass is maintained. When the amount of food in CANA-treated mice is adjusted to that in vehicle-treated mice, fast muscle mass and function are reduced, but slow muscle was unaffected during SGLT2 inhibition. In metabolome analysis, glycolytic metabolites and ATP are increased in fast muscle, whereas glycolytic metabolites are reduced but ATP is maintained in slow muscle during SGLT2 inhibition. Amino acids and free fatty acids are increased in slow muscle, but unchanged in fast muscle during SGLT2 inhibition. The metabolic effects on slow and fast muscles are exaggerated when food intake is restricted. This study demonstrates the differential effects of an SGLT2 inhibitor on slow and fast muscles independent of impaired glucose metabolism, thereby providing new insights into how they should be used in patients with diabetes, who are at a high risk of sarcopenia.

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Section: Methodsmentioning

confidence: 99%

“…amino acids, etc.) [ 70 , 71 ]. After the aqueous layer extracts were evaporated under vacuum, dried extracts were stored at −80°C until use for IC/MS and PFPP-LC/MS analysis.…”

Section: Methodsmentioning

confidence: 99%

Differential effect of canagliflozin, a sodium–glucose cotransporter 2 (SGLT2) inhibitor, on slow and fast skeletal muscles from nondiabetic mice

Otsuka

Yokomizo

Nakamura

et al. 2022

Biochemical Journal

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“…4 ). A previous report showed that ketone bodies were rapidly released from hepatocytes and were detected in the culture medium in vitro [ 15 ]. In fact, β-hydroxybutyrate in the gastrocnemius and plasma was significantly enhanced and remained high throughout the experiment ( Fig.…”

Section: Discussionmentioning

confidence: 99%

“…Three liquid chromatography mass spectrometry methods for metabolome analysis were employed as described previously [ 15 , 16 ]. Anionic polar metabolites (i.e., citrate, cis -aconitate, isocitrate, α-ketoglutarate, succinate, malate, fumarate, glucose) were analyzed using ion chromatography (Dionex ICS-5000 + HPIC system, Thermo Fisher Scientific, Waltham, MA, USA) with a Dionex IonPac AS11-HC-4 μm column (2 mm i.d.…”

Section: Methodsmentioning

confidence: 99%

Produced β-hydroxybutyrate after β-hydroxy-β-methylbutyrate (HMB) administration may contribute HMB function in mice

Ikeda

Takahashi

Aburaya

et al. 2021

Biochemistry and Biophysics Reports

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β-Hydroxy-β-methylbutyrate (HMB) is an intermediate in the metabolism of the branched-chain amino acid leucine. HMB has several demonstrated effects on skeletal muscle function, some of which are contradictory. In addition, the effect of exogenous HMB intake on the levels of intermediate metabolites is not known. Therefore, we investigated changes in HMB metabolites after oral HMB administration in mice. First, ICR mice were treated with either distilled water or HMB (0.215 g/10 mL/kg). Sampling was performed at 0, 1, 6, 12, and 24 h after administration. Next, ICR mice were given distilled water or HMB (0.215 g/10 mL/kg/d) for 10 d. Mice given HMB shown a significant increase in liver β-methylcrotonyl-CoA and increased β-hydroxybutyrate in plasma and the gastrocnemius muscle 1 h after HMB administration. Mice administered HMB for 10 d showed significantly decreased food intake and body weight; however, the relative weight of the gastrocnemius muscle was significantly increased. These results may be attributed to an increase in β-hydroxybutyrate resulting from exogenous HMB, since β-hydroxybutyrate inhibits food intake and suppresses skeletal muscle catabolism. In conclusion, β-hydroxybutyrate, a metabolite of HMB, was found to play an important role in the function of HMB.

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“…In this study, in the SFC/MS method (Method E), all lipid molecules in the same class were eluted at similar retention times by SFC-based lipid class separation [28]. Because this technique (Method E) co-elutes the same class of lipids, the ion-suppression and/or ion-enhancement effects of the biological matrix can be normalized by adding the appropriate internal standards of each lipid class (stable isotope-labeled lipid standards) [19,28]. However, in this study, to clarify the cause of the inconsistency in the relative quantification (S-1/S-3) results from the analytical methods, the relative quantification values were calculated using the raw data (peak area or height) without correcting the acquired data with the internal standards.…”

Section: Hydrophobic Metabolitesmentioning

confidence: 99%

Comparative Evaluation of Plasma Metabolomic Data from Multiple Laboratories

et al. 2022

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In mass spectrometry-based metabolomics, the differences in the analytical results from different laboratories/machines are an issue to be considered because various types of machines are used in each laboratory. Moreover, the analytical methods are unique to each laboratory. It is important to understand the reality of inter-laboratory differences in metabolomics. Therefore, we have evaluated whether the differences in analytical methods, with the exception sample pretreatment and including metabolite extraction, are involved in the inter-laboratory differences or not. In this study, nine facilities are evaluated for inter-laboratory comparisons of metabolomic analysis. Identical dried samples prepared from human and mouse plasma are distributed to each laboratory, and the metabolites are measured without the pretreatment that is unique to each laboratory. In these measurements, hydrophilic and hydrophobic metabolites are analyzed using 11 and 7 analytical methods, respectively. The metabolomic data acquired at each laboratory are integrated, and the differences in the metabolomic data from the laboratories are evaluated. No substantial difference in the relative quantitative data (human/mouse) for a little less than 50% of the detected metabolites is observed, and the hydrophilic metabolites have fewer differences between the laboratories compared with hydrophobic metabolites. From evaluating selected quantitatively guaranteed metabolites, the proportion of metabolites without the inter-laboratory differences is observed to be slightly high. It is difficult to resolve the inter-laboratory differences in metabolomics because all laboratories cannot prepare the same analytical environments. However, the results from this study indicate that the inter-laboratory differences in metabolomic data are due to measurement and data analysis rather than sample preparation, which will facilitate the understanding of the problems in metabolomics studies involving multiple laboratories.

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Dynamic Metabolome Analysis Reveals the Metabolic Fate of Medium-Chain Fatty Acids in AML12 Cells

Cited by 34 publications

References 68 publications

Differential effect of canagliflozin, a sodium–glucose cotransporter 2 (SGLT2) inhibitor, on slow and fast skeletal muscles from nondiabetic mice

Differential effect of canagliflozin, a sodium–glucose cotransporter 2 (SGLT2) inhibitor, on slow and fast skeletal muscles from nondiabetic mice

Produced β-hydroxybutyrate after β-hydroxy-β-methylbutyrate (HMB) administration may contribute HMB function in mice

Comparative Evaluation of Plasma Metabolomic Data from Multiple Laboratories

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