Interaction of n-3 polyunsaturated fatty acids with host CD36 genetic variant for gut microbiome and blood lipids in human cohorts

Omega-3 fatty acids and individual variability in plasma triglyceride response: A mini-review

“…The TG response after omega-3 supplementation has been shown to interact with sex and apolipoprotein E ( APOE ) genotype, with ApoE4 males having the most significant TG reduction [ 32 ]. Moreover, SNPs in nitric oxide synthase 3 ( NOS3 ), CD36 molecule ( CD36 ) and lymphotoxin alpha ( LTA , also known as TNFβ) are associated with the TG response to omega-3 supplementation [ [34] , [35] , [36] , [37] ]. In a Canadian study, 208 participants were supplemented with 5 g fish oil dayily (∼2 g EPA + 1 g DHA) for 6 weeks.…”

“… Ferguson et al, 2010 [ 34 ] Plasma TG concentrations of minor allele carriers (AC + AA) of the NOS3 rs1799983 SNP were more responsive to changes in plasma n-3 PUFA, than major allele (CC) homozygotes after omega-3 supplementation. Madden et al, 2008 [ 35 ] Significant TG reduction following omega-3 supplementation only occurred in individuals with the GG variant of the 25444G > A, 30294G > C, 31118G > A and 33137A > G SNPs of the CD36 gene Miao et al, 2022 [ 36 ] Omega-3 exposure in the top quartile was associated with lower TG concentrations compared to the bottom quartile among CD36 rs1527483-GG carriers, but not in AA/AG carriers. Marcovic et al, 2004 [ 37 ] Across all BMI tertiles, TG reduction after omega-3 supplementation occurred only in individuals possessing the AA genotype in position +252 of LTA , encoding TNFβ.…”

“…and this change negatively correlated with the VLDL and VLDL-TG response after omega-3 supplementation. Miao et al, 2022 [ 36 ] The CD36 rs1527483 variant interacted with the change in diversity and levels of Dorea and Coriobacteriales Incertae Sedis spp , and TG response after omega-3 supplementation. Habitual diet associations with TG response to omega-3 Rudkowska et al, 2013 [ 30 ] DHA in red blood cells increased after omega-3 supplementation in TG responders to omega-3 supplementation, but not in non-responders.…”

“…A cohort study found a negative association between omega-3 exposure and plasma TG levels in carriers of a CD36 genetic variant. The same SNP also interacted with associations between DHA exposure and microbial features such as higher phylogenetic diversity and higher levels of Dorea and Coriobacteriales Incertae Sedis spp [ 36 ]. Finally, omega-3 supplementation has been shown to decrease microbial diversity and increased Bifidobacteria .…”

Exploring a novel therapeutic strategy: the interplay between gut microbiota and high-fat diet in the pathogenesis of metabolic disorders

“…CD36, a transmembrane glycoprotein, is widely distributed in the body and plays a role in lipid metabolism as a scavenger receptor. Zelei Miao et al conducted a cohort study and found that higher n-3 polyunsaturated fatty acid (n-3 PUFA) levels in CD36 rs1527483-GG carriers were associated with improvements in blood lipids and gut microbiota characteristics ( 225 ). These findings emphasize the potential role of the gut microbiota in linking CD36 gene polymorphisms, n-3 PUFAs, and blood lipid metabolism, providing evidence for the importance of the HFD-gut microbiota-gene axis in blood lipid metabolism.…”