Table 2 Sexual dimorphism in four main cardiovascular disease-related metabolites

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 [62,63,64].