Table 4 Functional significance of select metabolites
Metabolite | Biological pathway/function | Direction of change with OGTT (fold change) (%) | Direction of association of change after OGTT with | Biological functions and previous association with CVD and cardiometabolic disease | |
|---|---|---|---|---|---|
CVD | Mortality | ||||
Glutamate | Glutamate/glutamine cycle | ↓ (20) | ↑ | Contributes to gluconeogenesis, proteolysis, inflammation [52, 53], cellular metabolism (anaplerosis); high fasting glutamate associated with higher CVD and diabetes risk [39, 40] | |
Inosine | Nucleoside | ↓ (58) | ↓ | Intermediate in purine biosynthesis and secondary metabolite of purine degradation (from hypoxanthine); fasting levels higher in diabetes, but theorized to have cardioprotective effects [56, 57] | |
Deoxycholate | Bile acid | ↓ (28) | ↑ | Product of cholesterol metabolism; higher fasting levels linked with diabetes risk [54]; total bile acids associated with CVD [58]; pro-inflammatory [59] | |
Phosphatidylcholine (PC) 32:0 | Glycerophospholipid | ↓ (4) | ↓ | Structural role in cell membranes; reservoir for circulating fatty acids [60]; several PCs have been associated (both directly and inversely) with CVD with direct mechanisms unknown [61] | |
LysoPC 18:2 | Glycerophospholipid | ↓ (4) | ↓ | Produced from partial hydrolysis of PCs; bioactive lipid involved in monocyte recruitment, vascular smooth muscle proliferation, endothelial dysfunction; fasting levels associated with lower risk of atherosclerosis [60, 62] | |
Hydroxy phenylacetate | Phenol | ↓ (18) | ↑ | Derived from acetate metabolism; implicated in CVD risk and unhealthy aging [36, 37], affected by microbial metabolism [63] | |
Triacylglycerol (TAG) 56:5 | Triacylglycerol | ↑ (8) | ↑ | TAG species demonstrate different associations with cardiometabolic disease; lower carbon number and double bond content associated with insulin resistance and higher diabetes risk [13]; uptake from blood stimulated by the liver so increased circulating after a meal may partially reflect insulin resistance [64] | |
Glucuronate | Vitamin C precursor | ↓ (10) | ↓ | Derived from glucose, aids in the elimination of toxins; plasma levels have been previously related to reduced longevity [65] | |
⍺-Ketoglutarate | Tricarboxylic acid cycle intermediate | ↓ (7) | ↑ | Various metabolic functions including central metabolism, collagen synthesis, stem cell proliferation, and epigenetic regulation; leads to extended lifespan in mice [38]; in nutrient excess, promotes branched-chain amino acid catabolism [14]; stimulates autophagy [66] | |
NMMA (N-monomethyl-arginine) | Arginine derivative | ↓ (20) | ↓ | Inhibitor of nitric oxide and potent vasoconstrictor [67]; exogenous administration leads to early satiety [68] | |