Metabolic profiling in the hypothalamus of aged mice

Kim, Ye Jin; Park, Byong Seo; Song, Nuri; Tu, Thai Hien; Lee, Sewon; Kim, Jae Kwang

doi:10.1016/j.bbrc.2022.02.042

Cited by 3 publications

(1 citation statement)

References 29 publications

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“…Mass spectrometry (MS) coupled with gas chromatography (GC) is widely used in the complex structure analysis of biological samples [17]. Metabolic studies of fever have mainly focused on biohumoral samples and tissues, such as serum, plasma, urine, brain and hypothalamus [18][19][20][21]. Serum samples are easy to obtain, free from fibrinogen, and contain more than 1000 endogenous small molecule metabolites, which is an important metabolomic body fluid sample.…”

Section: Introductionmentioning

confidence: 99%

Serum Metabolomics Based on GC-MS Reveals the Antipyretic Mechanism of Ellagic Acid in a Rat Model

Xie

Zhu

et al. 2022

Metabolites

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Ellagic acid (EA) is a polyphenol dilactone that has been reported to have antipyretic, anti-inflammatory, anti-tumor, and antioxidant activities, but the mechanism of action has not been reported. In this study, serum metabolomics was used to explore the mechanism of EA on rat fever induced by beer yeast, and to screen out marker metabolites to provide a reference for the antipyretic effect of EA. The acute fever model of male Sprague Dawley rats involved subcutaneous injection with 20% aqueous suspension of yeast (15 mL/kg) in their back. At the same time of modeling, EA was given orally by 10 mL/kg intragastric administration for treatment. During the experiment, the temperature and its change values of rats were recorded, and Interleukin-6 (IL-6), Tumor Necrosis Factor-α (TNF-α), Prostaglandin E2 (PGE2), Cyclic Adenosine Monophosphate (cAMP), Superoxide Dismutase (SOD) and Malondialdehyde (MDA)—six physiological and biochemical indexes of rats—were detected after the experiment. In addition, the hypothalamus of each rat was analyzed by Western blot (WB), and the levels of Phospho Nuclear Factor kappa-B (P-NF-κB P65) and IkappaB-alpha (IKB-α) were detected. Then, the serum metabolites of rats in each group were detected and analyzed by gas chromatograph mass spectrometry and the multivariate statistical analysis method. Finally, when screening for differential metabolites, the potential target metabolic pathway of drug intervention was screened for through the enrichment analysis of differential metabolites. Pearson correlation analysis was used to systematically characterize the relationship between biomarkers and pharmacodynamic indicators. EA could reduce the temperature and its change value in yeast induced fever rats after 18 h (p < 0.05). The level of IL-6, TNF-α, PGE2, cAMP, SOD and MDA of the Model group (MG) increased significantly compared to the Normal group (NG) (p < 0.001) after EA treatment, while the levels of the six indexes in the serum and cerebrospinal fluid of yeast-induced rats decreased. The administration of yeast led to a significant increase in Hypothalamus P-NF-κB P65 and IKB-α levels. Treatment with EA led to a significant decrease in P-NF-κB P65 levels. Moreover, combined with VIP > 1 and p < 0.05 as screening criteria, the corresponding retention time and characteristic mass to charge ratio were compared with the NIST library, Match score > 80%, and a total of 15 differential metabolites were screened. EA administration significantly regulated 9 of 15 metabolites in rat serum. The 15 differential metabolites involved linoleic acid metabolism, phenylalanine, tyrosine and tryptophan biosynthesis, galactose metabolism, biosynthesis of unsaturated fatty acids and glycerolipid metabolism. Pharmacodynamic correlation analysis was conducted between 15 different metabolites and six detection indexes. There was a significant correlation between 13 metabolites and six detection indexes. D-(−)-lactic acid, glycerin, phosphoric acid, 5-oxo-L-proline were negatively correlated with TNF-α, and p values were statistically significant except for L-tyrosine. In addition, glycerin was negatively correlated with IL-6, PGE2 and MDA, while phosphoric acid was negatively correlated with IL-6. In conclusion, EA may play an antipyretic anti-inflammatory role through the inhibition of the IKB-α/NF-κB signaling pathway and five metabolic pathways, which may contribute to a further understanding of the therapeutic mechanisms of the fever of EA.

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Section: Introductionmentioning

confidence: 99%

Serum Metabolomics Based on GC-MS Reveals the Antipyretic Mechanism of Ellagic Acid in a Rat Model

Xie

Zhu

et al. 2022

Metabolites

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Comparative metabolomic analysis of mouse plasma in response to different dietary conditions

Yang,

Kim,

Lee

et al. 2023

Food Sci Biotechnol

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Evaluation of obesity prevention effect of black ginseng on serum, liver, and hypothalamus of mice on a high-fat diet using a metabolomics approach

Kim,

Lee,

Yang

et al. 2023

Appl Biol Chem

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Black ginseng is being studied to prevent obesity caused by a high-fat diet (HFD). The aim of this study was to evaluate the obesity-preventing effect of black ginseng extract (BGE) in the serum, liver, and hypothalamus of mice on an HFD using metabolomic techniques. Mice were divided into four groups which were respectively fed a normal diet (CTL), an HFD, an HFD with a low concentration of BGE (BGEL), and an HFD with a high concentration of BGE (BGEH) for 8 weeks. Metabolite profiling revealed a clear separation between the BGE diet and HFD groups. Lipid metabolism, including saturated fatty acids and cholesterol, was decreased in the BGEH mice. Specifically, neurotransmitters and intermediates of the tricarboxylic acid cycle were increased in the hypothalamus of BGEH mice. The results suggest the obesity prevention effect of black ginseng in that BGEH inhibits body fat accumulation and restores brain function damaged by HFD.

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Metabolic profiling in the hypothalamus of aged mice

Cited by 3 publications

References 29 publications

Serum Metabolomics Based on GC-MS Reveals the Antipyretic Mechanism of Ellagic Acid in a Rat Model

Serum Metabolomics Based on GC-MS Reveals the Antipyretic Mechanism of Ellagic Acid in a Rat Model

Comparative metabolomic analysis of mouse plasma in response to different dietary conditions

Evaluation of obesity prevention effect of black ginseng on serum, liver, and hypothalamus of mice on a high-fat diet using a metabolomics approach

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