Dataset Information

Medium- and long-chain triacylglycerols and di-unsaturated fatty acyl-palmitoyl-glycerols in Chinese human milk: Association with region during the lactation.

ABSTRACT: The triacylglycerols (TAGs) of medium- and long-chain triacylglycerols (MLCT) and di-unsaturated fatty acyl-palmitoyl-glycerols (UPU) in human milk provide better nutritional effects, and should be prioritized as crucial focuses on neonatal nutrition research. However, little has been done on the influences of the lactation stage and regional diversity on MLCT and UPU. In this study, we collected 204 human milk samples during colostrum, 1st and 4th month from the north (Baotou), central (Beijing), east (Jinan), southwest (Kunming), southeast (Shenzhen), and northwest (Xining) regions of China. There were 122 species of TAGs detected with UPLC-Q-TOF-MS, including 60 kinds of MLCT and 15 kinds of UPU. The MLCT and UPU type TAGs in human milk were ~27 and ~38%, respectively. The sum content of MLCT and UPU in human milk was stable. Compared to the regional diversity, lactation stages showed more obvious influences on MLCT and UPU composition. Moreover, a summary of TAG studies indicated that Chinese human milk showed a higher ratio of O-P-L to O-P-O than in western countries.

SUBMITTER: Yu J

PROVIDER: S-EPMC9614417 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Medium- and long-chain triacylglycerols and di-unsaturated fatty acyl-palmitoyl-glycerols in Chinese human milk: Association with region during the lactation.

Yu Jiahui J Yan Zhiyuan Z Mi Lijuan L Wang Lei L Liu Zhengdong Z Ye Xingwang X Jin QingZhe Q Pang Jinzhu J Wei Wei W Wang Xingguo X

Frontiers in nutrition 20221014

The triacylglycerols (TAGs) of medium- and long-chain triacylglycerols (MLCT) and di-unsaturated fatty acyl-palmitoyl-glycerols (UPU) in human milk provide better nutritional effects, and should be prioritized as crucial focuses on neonatal nutrition research. However, little has been done on the influences of the lactation stage and regional diversity on MLCT and UPU. In this study, we collected 204 human milk samples during colostrum, 1st and 4th month from the north (Baotou), central (Beijing ...[more]

PMID: 36313110

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Project description:Triheptanoin (triheptanoylglycerol) has shown value as anaplerotic therapy for patients with long chain fatty acid oxidation disorders but is contraindicated in medium-chain acyl-CoA dehydrogenase (MCAD) deficiency. In search for anaplerotic therapy for patients with MCAD deficiency, fibroblasts from three patients homozygous for the most common mutation, ACADMG985A/G985A, were treated with fatty acids hypothesized not to require MCAD for their metabolism, including heptanoic (C7; the active component of triheptanoin), 2,6-dimethylheptanoic (dMC7), 6-amino-2,4-dimethylheptanoic (AdMC7), or 4,8-dimethylnonanoic (dMC9) acids. Their effectiveness as anaplerotic fatty acids was assessed in live cells by monitoring changes in cellular oxygen consumption rate (OCR) and mitochondrial protein lysine succinylation, which reflects cellular succinyl-CoA levels, using immunofluorescence (IF) staining. Krebs cycle intermediates were also quantitated in these cells using targeted metabolomics. The four fatty acids induced positive changes in OCR parameters, consistent with their oxidative catalysis and utilization. Increases in cellular IF staining of succinylated lysines were observed, indicating that the fatty acids were effective sources of succinyl-CoA in the absence of media glucose, pyruvate, and lipids. The ability of MCAD deficient cells to metabolize C7 was confirmed by the ability of extracts to enzymatically utilize C7-CoA as substrate but not C8-CoA. To evaluate C7 therapeutic potential in vivo, Acadm-/- mice were treated with triheptanoin for seven days. Dose dependent increase in plasma levels of heptanoyl-, valeryl-, and propionylcarnitine indicated efficient metabolism of the medication. The pattern of the acylcarnitine profile paralleled resolution of liver pathology including reversing hepatic steatosis, increasing hepatic glycogen content, and increasing hepatocyte protein succinylation, all indicating improved energy homeostasis in the treated mice. These results provide the impetus to evaluate triheptanoin and the medium branched chain fatty acids as potential therapeutic agents for patients with MCAD deficiency.

Project description:BackgroundMonogenetic inborn errors of metabolism cause a wide phenotypic heterogeneity that may even differ between family members carrying the same genetic variant. Computational modelling of metabolic networks may identify putative sources of this inter-patient heterogeneity. Here, we mainly focus on medium-chain acyl-CoA dehydrogenase deficiency (MCADD), the most common inborn error of the mitochondrial fatty acid oxidation (mFAO). It is an enigma why some MCADD patients-if untreated-are at risk to develop severe metabolic decompensations, whereas others remain asymptomatic throughout life. We hypothesised that an ability to maintain an increased free mitochondrial CoA (CoASH) and pathway flux might distinguish asymptomatic from symptomatic patients.ResultsWe built and experimentally validated, for the first time, a kinetic model of the human liver mFAO. Metabolites were partitioned according to their water solubility between the bulk aqueous matrix and the inner membrane. Enzymes are also either membrane-bound or in the matrix. This metabolite partitioning is a novel model attribute and improved predictions. MCADD substantially reduced pathway flux and CoASH, the latter due to the sequestration of CoA as medium-chain acyl-CoA esters. Analysis of urine from MCADD patients obtained during a metabolic decompensation showed an accumulation of medium- and short-chain acylcarnitines, just like the acyl-CoA pool in the MCADD model. The model suggested some rescues that increased flux and CoASH, notably increasing short-chain acyl-CoA dehydrogenase (SCAD) levels. Proteome analysis of MCADD patient-derived fibroblasts indeed revealed elevated levels of SCAD in a patient with a clinically asymptomatic state. This is a rescue for MCADD that has not been explored before. Personalised models based on these proteomics data confirmed an increased pathway flux and CoASH in the model of an asymptomatic patient compared to those of symptomatic MCADD patients.ConclusionsWe present a detailed, validated kinetic model of mFAO in human liver, with solubility-dependent metabolite partitioning. Personalised modelling of individual patients provides a novel explanation for phenotypic heterogeneity among MCADD patients. Further development of personalised metabolic models is a promising direction to improve individualised risk assessment, management and monitoring for inborn errors of metabolism.

Dataset Information

Medium- and long-chain triacylglycerols and di-unsaturated fatty acyl-palmitoyl-glycerols in Chinese human milk: Association with region during the lactation.

Publications

Medium- and long-chain triacylglycerols and di-unsaturated fatty acyl-palmitoyl-glycerols in Chinese human milk: Association with region during the lactation.

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