Resveratrol intervention attenuates chylomicron secretion via repressing intestinal FXR-induced expression of...

Area of Science:

• Biochemistry
• Microbiology
• Nutrition Science

Background:

• Dietary polyphenols offer health benefits but their mechanisms are unclear due to multi-organ effects and low bioavailability.
• Resveratrol is a polyphenol with potential health benefits, but its precise mode of action requires elucidation.

Purpose of the Study:

• To investigate the mechanism by which resveratrol intervention (REV-I) affects lipid homeostasis.
• To determine if the gut microbiome or direct cellular effects are the primary target of REV-I.

Main Methods:

• High-fat diet (HFD)-challenged male mice were used, including intestinal mucosa-specific scavenger receptor class B type 1 knockout (SR-B1-/-) mice.
• Experiments involved resveratrol intervention (REV-I), fecal-microbiota transplantation, and Caco-2 cell studies with chenodeoxycholic acid treatment.

Main Results:

• REV-I inhibited chylomicron secretion and reduced jejunal SR-B1 expression in HFD mice.
• Intestinal SR-B1 knockout mice showed improved lipid homeostasis but no further response to REV-I.
• REV-I reduced fecal bile acids and bile-salt hydrolase activity, suggesting gut microbiome involvement.
• Chenodeoxycholic acid stimulated both FXR and SR-B1 in Caco-2 cells.

Conclusions:

• The gut microbiome is the primary target of resveratrol intervention (REV-I).
• REV-I improves lipid homeostasis partly by reducing FXR-stimulated elevation of gut SR-B1.
• These findings highlight the role of the gut microbiome in mediating the effects of dietary polyphenols.