Untargeted Metabolomics Analysis Using UHPLC-Q-TOF/MS Reveals Metabolic Changes Associated with Hypertension in Children

Abstract

The mechanism of hypertension in children remains elusive. The objective of this study was to analyze plasma metabolomics characteristics to explore the potential mechanism of hypertension in children. Serum samples from 29 control children, 38 children with normal body mass index and simple hypertension (NBp), 8 children overweight with simple hypertension (OBp), 37 children with normal body mass index and H-type hypertension (NH) and 19 children overweight with H-type hypertension (OH) were analyzed by non-targeted metabolomics. A total of 1235 differential metabolites were identified between children with hypertension and normal controls, of which 193 metabolites including various lipids were significantly expressed. Compared with the control group, 3-dehydroepiandrosterone sulfate, oleic acid and linoleic acid were up-regulated, and gamma-muricholic acid was down-regulated in the NBp group; 3-dehydroepiandrosterone sulfate, 4-acetamidobutanoate and 1-hexadecanoyl-2-octadecadienoyl-sn-glyero-3-phosphocholine were up-regulated in the OBp group, whereas adenosine and 1-myristoyl-sn-glyero-3-phosphocholine were down-regulated; in the NH group, 1-palmitoyl-2-linoleoyl-sn-glycero-3-phosphocholine, phenol and 3-methoxytyramine were up-regulated, while pentadecanoic acid was down-regulated; in the OH group, NG,NG-dimethyl-L-arginine, 1-palmitoyl-sn-glycero-3-phosphocholine and monoethyl phthalate were up-regulated, while phloretin and glycine were down-regulated. The results showed that the children with hypertension had obvious disorders of lipid metabolism (especially in the overweight hypertension group), which led to the occurrence of hypertension. Additionally, the concentration of NO production-related NG, NG-dimethyl-L-arginine, was significantly increased, which may play an important role in H-type hypertension in children.

Exploring the causal role of multiple metabolites on ovarian cancer: a two sample Mendelian randomization study

“…Notably, in a study on unique metabolomic characteristics related to cirrhosis mortality [ 36 ], 4-acetamidobutanoate significantly predicted mortality. It's reported that in patients with acute kidney injury (AKI), 4-acetamidobutanoate increased 12-fold [ 37 ], and its levels significantly increased in patients with morbid hypertension [ 38 ]. Similarly, alpha-hydroxyisovalerate, an organic acid related to branched-chain amino acid metabolism, has been linked with liver injury [ 39 ], diabetic nephropathy [ 40 ], and Maple Syrup Urine Disease [ 41 ].…”

Polar metabolomics using trichloroacetic acid extraction and porous graphitic carbon stationary phase

“…Our results compare well with results of HILIC or derivatisation-GC–MS methods (Rakusanova et al, 2023 ; Zeki et al, 2020 ). For example, Zhang et al ( 2023 ) detected 755 positive ions in serum samples from 131 hypertensive children. The sample preparation required drying and reconstitution of the serum extract whereas our method involves a simple single extraction and centrifugation step, that can be completed within 15 minutes and immediately analysed.…”