Key result
The ANGPTL8 rs2278426 variant (CT+TT) was associated with statistically significant differences in lipid- and inflammation-related plasma metabolites compared to the reference genotype (CC).
Why the study?
ANGPTL8 regulates lipid metabolism and its R59W variant associates with lipid traits across ethnicities, but its impact on human metabolites remains incompletely understood.
Does the ANGPTL8 R59W variant alter plasma metabolite profiles in adult male Arab individuals?
Observational (n=60)
Does the ANGPTL8 R59W variant alter plasma metabolite profiles in adult male Arab individuals?
The ANGPTL8 R59W variant significantly influences the concentrations of lipid- and inflammation-related metabolites, highlighting its role in lipid metabolism.
Variant alters lipid/inflammation metabolites in Arabs; hypothesis-generating for ANGPTL8 function, needs larger validation before clinical relevance.
ANGPTL8 is recognized as a regulator of lipid metabolism through its role in inhibiting lipoprotein lipase activity. ANGPTL8 gene variants, particularly rs2278426 leading to the R59W variant in the protein, have been associated with lipid traits in various ethnicities. We aimed to use metabolomics to understand the impact of the ANGPTL8 R59W variant on metabolites in humans. We used the Biocrates-p400 kit to quantify 408 plasma metabolites in 60 adult male Arab individuals from Kuwait and identify differences in metabolite levels between individuals carrying reference genotypes and those with carrier genotypes at ANGPTL8 rs2278426. Individuals with carrier genotypes (CT+TT) compared to those carrying the reference genotype (CC) showed statistically significant differences in the following metabolites: acylcarnitine (perturbs metabolic pathways), phosphatidylcholine (supports liver function and cholesterol levels), cholesteryl ester (brings chronic inflammatory response to lipoprotein depositions in arteries), α-aminoadipic acid (modulates glucose homeostasis), histamine (regulates glucose/lipid metabolism), sarcosine (links amino acid and lipid metabolism), diacylglycerol 42:1 (regulates homeostasis of cellular lipid stores), and lysophosphatidylcholine (regulates oxidative stress and inflammatory response). Functional aspects attributed to these metabolites indicate that the ANGPTL8 R59W variant influences the concentrations of lipid- and inflammation-related metabolites. This observation further highlights the role of ANGPTL8 in lipid metabolism.
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Abu‐Farha et al. (2023) reported an observational. ANGPTL8 rs2278426 carrier genotypes (CT+TT) vs. Reference genotype (CC) was evaluated on Differences in plasma metabolite levels. The ANGPTL8 rs2278426 variant (CT+TT) was associated with statistically significant differences in lipid- and inflammation-related plasma metabolites compared to the reference genotype (CC).
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