Table 2.

Sexual dimorphism in four main cardiovascular disease-related metabolites

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