Serum metabolomics of hyperbilirubinemia and hyperuricemia in the Tibetan plateau has unique characteristics

Abstract

Few studies have provided data on the metabolomics characteristics of metabolic diseases such as hyperuricemia and hyperbilirubinemia in the Tibetan plateau. In the current study, we sought to investigate the serum metabolomics characteristics of hyperbilirubinemia and hyperuricemia in the Tibetan plateau, with the aim to provide a basis for further research on their pathogenesis, prevention, and treatment. The study participants were born in low-altitude areas below 1000 m and had no prior experience living in a high-altitude area before entering Golmud, Tibet (average elevation: 3000 m) and Yushu, Qinghai (average elevation: 4200 m). Thirty-four participants with hyperbilirubinemia (18 in Golmud and 16 in Yushu), 24 participants with hyperuricemia, and 22 healthy controls were enrolled. The serum samples of subjects were separated and then sent to a local tertiary hospital for biochemical examination. Serum widely targeted technology, based on the ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) platform, was used to detect serum metabolites and differential metabolites. Compared to the healthy controls, hyperbilirubinemia patients from Golmud showed 19 differential metabolites, hyperbilirubinemia patients from Yushu showed 12 differential metabolites, and hyperuricemia patients from Yushu showed 23 differential metabolites. Compared to the hyperbilirubinemia patients from Golmud that is at a low altitude, the Yushu groups had 33 different metabolites. Differential metabolites are primarily classified into amino acids and their derivatives, nucleotides and their derivatives, organic acids and their derivatives, and lipids/fatty acids. These are related to metabolic pathways such as caffeine metabolism, arachidonic acid metabolism, and tyrosine metabolism. Hyperbilirubinemia and hyperuricemia in the Tibetan plateau have unique serum metabolomics characteristics. Glycine derivatives and arachidonic acid and its derivatives were associated with plateau hyperbilirubinemia, and vanillic acid and pentadecafluorooctanoic acid were associated with plateau hyperuricemia.

Gender-specific association between blood cell parameters and hyperuricemia in high-altitude areas

“…Previous studies have shown regional and population disparities in the incidence of hyperuricemia in China ( 16 , 17 ). Notably, the Tibetan population in high-altitude areas exhibits different rates compared to the Han population in lowland regions ( 18 , 19 ). A multicenter study involving a large sample size demonstrated that Tibetan males have a higher incidence of hyperuricemia compared to Han males, while Tibetan females have a lower incidence of hyperuricemia than Han females ( 18 ).…”

Serum metabolite changes are implicated in high-altitude acclimatization and de-acclimatization

“…Uric acid is produced via purine base catalysis by different enzymes, while highaltitude exposure increases hyperuricemia risks [46]. High-altitude exposure also alters metabolic characteristics in the body, disrupts energy metabolism, and induces inflammatory responses [31].…”

Bifidobacterium animalis subsp. lactis F1–7 Alleviates Lipid Accumulation in Atherosclerotic Mice via Modulating Bile Acid Metabolites to Downregulate Intestinal FXR

“…The VIP values were extracted from the OPLS-DA result, which generated using the R package MetaboAnalystR. The fold change value, metabolites with VIP > 1, and fold change ≥2 or ≤0.5 were selected as differential metabolites between the groups . The metabolites were identified based on KEGG compound database.…”

“…The fold change value, metabolites with VIP > 1, and fold change ≥2 or ≤0.5 were selected as differential metabolites between the groups. 20 The metabolites were identified based on KEGG compound database. Then the identified metabolites were classified pathways based on the KEGG pathway database.…”