Table 2.
Metabolite | Men | Women | Cardiovascular disease risk |
---|---|---|---|
Branched-chain amino acids |
↑ Serum branched-chain amino acids ↓ Branched-chain 2-oxoacid dehydrogenase |
↓ Serum branched-chain amino acids ↑ Branched-chain 2-oxo acid dehydrogenase |
Increased risk of insulin resistance and type II diabetes in men compared to women - Possible mechanisms include female sex hormone regulation of branched-chain 2-oxoacid dehydrogenase and enrichment of the gut microbial Bacteroides-Prevotella group in men [30, 72]. |
Short-chain fatty acids |
↓ Short-chain fatty acids ↓ Dietary fiber intake ↓ PPAR-γ |
↑ Short-chain fatty acids ↑ Dietary fiber intake ↑ PPAR-γ |
Increased susceptibility to dyslipidemia in men compared to women - Possible mechanisms include 17β-estradiol-mediated increase in PPAR-γ receptor expression and decreased dietary fiber intake in men [20, 82]. |
Trimethylamine N-oxide |
↓ TLR expression ↓ FMO3 expression ↓ Secondary bile acids |
↑ TLR expression ↑ FMO3 expression ↑ Secondary bile acids |
Greater thrombotic risk in women compared to men - Possible mechanism: increased TLR and trimethylamine N-oxide activation of platelets. [54, 55]. Accelerated trimethylamine N-oxide production in women compared to men - Possible mechanisms: gonadal hormone regulation of hepatic FMO3 expression and increased secondary bile acid activation of Farnesoid X receptor [43, 87]. |
Lipopolysaccharide |
↓ TLR4 expression ↓ TLR2 signaling |
↑ TLR4 expression ↑ TLR2 signaling |
Estrogens, progesterone, and testosterone regulate LPS-mediated signaling through TLR4 [62–64]. |
FMO3 flavin monooxygenase-3, PPAR-γ peroxisome proliferator activating receptor gamma, TLR toll-like receptor