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在肥胖女性队列中分析血浆和组织代谢组之间的关系:对皮下和内脏脂肪、肌肉和肝脏进行分析。

Dissecting the relationship between plasma and tissue metabolome in a cohort of women with obesity: Analysis of subcutaneous and visceral adipose, muscle, and liver.

机构信息

Food Chemistry and Structure, AgResearch Limited, Palmerston North, New Zealand.

School of Health Sciences, Massey University, Palmerston North, New Zealand.

出版信息

FASEB J. 2022 Jul;36(7):e22371. doi: 10.1096/fj.202101812R.

DOI:10.1096/fj.202101812R
PMID:35704337
Abstract

Untargeted metabolomics of blood samples has become widely applied to study metabolic alterations underpinning disease and to identify biomarkers. However, understanding the relevance of a blood metabolite marker can be challenging if it is unknown whether it reflects the concentration in relevant tissues. To explore this field, metabolomic and lipidomic profiles of plasma, four sites of adipose tissues (ATs) from peripheral or central depot, two sites of muscle tissue, and liver tissue from a group of nondiabetic women with obesity who were scheduled to undergo bariatric surgery (n = 21) or other upper GI surgery (n = 5), were measured by liquid chromatography coupled with mass spectrometry. Relationships between plasma and tissue profiles were examined using Pearson correlation analysis subject to Benjamini-Hochberg correction. Plasma metabolites and lipids showed the highest number of significantly positive correlations with their corresponding concentrations in liver tissue, including lipid species of ceramide, mono- and di-hexosylceramide, sphingomyelin, phosphatidylcholine (PC), phosphatidylethanolamine (PE), lysophosphatidylethanolamine, dimethyl phosphatidylethanolamine, ether-linked PC, ether-linked PE, free fatty acid, cholesteryl ester, diacylglycerol and triacylglycerol, and polar metabolites linked to several metabolic functions and gut microbial metabolism. Plasma also showed significantly positive correlations with muscle for several phospholipid species and polar metabolites linked to metabolic functions and gut microbial metabolism, and with AT for several triacylglycerol species. In conclusion, plasma metabolomic and lipidomic profiles were reflective more of the liver profile than any of the muscle or AT sites examined in the present study. Our findings highlighted the importance of taking into consideration the metabolomic relationship of various tissues with plasma when postulating plasma metabolites marker to underlying mechanisms occurring in a specific tissue.

摘要

非靶向代谢组学分析已广泛应用于研究疾病相关的代谢变化,并用于鉴定生物标志物。然而,如果不知道血液代谢物标志物是否反映了相关组织中的浓度,那么理解其相关性可能具有挑战性。为了探索这一领域,我们对 21 名肥胖且拟行减重手术(n=21)或其他上消化道手术(n=5)的女性非糖尿病患者的血浆、外周或中央脂肪组织(AT)的四个部位、两个肌肉组织部位和肝组织的代谢组学和脂质组学图谱进行了分析,采用液相色谱-质谱联用技术进行检测。采用经 Benjamini-Hochberg 校正的 Pearson 相关分析来检验血浆和组织图谱之间的关系。血浆代谢物和脂质与肝组织中相应浓度的相关性最高,包括神经酰胺、单和二己糖神经酰胺、神经鞘磷脂、磷脂酰胆碱(PC)、磷脂酰乙醇胺(PE)、溶血磷脂酰乙醇胺、二甲基磷脂酰乙醇胺、醚连接的 PC、醚连接的 PE、游离脂肪酸、胆固醇酯、二酰基甘油和三酰基甘油,以及与多种代谢功能和肠道微生物代谢相关的极性代谢物。血浆与肌肉组织中的几种磷脂和与代谢功能和肠道微生物代谢相关的极性代谢物也呈显著正相关,与 AT 中的几种三酰基甘油也呈显著正相关。总之,与本研究中检查的任何肌肉或 AT 部位相比,血浆代谢组学和脂质组学图谱更能反映肝脏图谱。我们的研究结果强调了在提出特定组织中潜在机制的血浆代谢物标志物时,考虑各种组织与血浆之间代谢关系的重要性。

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