Dysbiosis of gut microbiota plays an essential role in cardiovascular diseases, but the molecular mechanisms are complex. An association between the gut microbiome and the variance in HDL-C (high-density lipoprotein-cholesterol) level was suggested in a human study. This study aimed to investigate and examine how and whether a high-fat diet (HFD) associated gut microbiota regulated the HDL-C levels.
The HFD led to increased amount of hepatic flagellin, and deletion of TLR5 (Toll-like receptor 5), suppressed HFD-stimulated ApoA1 (apolipoprotein A1) and HDL-C levels. The overexpression of TLR5 in the liver of the mice was able to restore HDL-C and ApoA1 production levels. Flagellin activated TLR5 in the primary hepatocytes stimulated ApoA1 production through the transcriptional activation responding to the binding of NF-κB on the Apoa1 promoter region. The stimulation of ApoA1 production was also observed in human ApoA1-transgenic mice treated with oral flagellin.
In conclusion, the mutualistic flagellated bacteria in the gut readily responds to dietary fat, triggering an increase in the HDL-C level. Such elevated levels of HDL-C might serve as a preventive mechanism for high-fat induced dyslipidemia. TLR5 might serve as a potential therapeutic target to increase ApoA1/HDL level. The search for synthetic TLR5 agonists with selective action on hepatocytes should be warranted, for the stimulation of ApoA1 production.
Ref: https://www.ahajournals.org/doi/10.1161/CIRCRESAHA.120.317362
